Blood Pressure Regulation Research Articles

Role of anxiolytic medications in maintaining perioperative blood pressure in total hip arthroplasty surgeries: case-control retrospective study

Background: Elevated blood pressure (BP) measurements seen in patients having total hip arthroplasty (THA), pose a significant issue for surgeons. The study objective was to investigate the effectiveness of preoperative anxiolytic medications in the maintenance of blood pressure and reduction of total blood loss in patients undergoing THA surgeries. Methods: A retrospective case-control cohort study in a tertiary care university hospital included patients who had THA and had either primary managed hypertension or were non-hypertensive. 190 patients who underwent primary THR; 103 controls and 87 treatment group (Oral 3 mg Bromazepam). Pearson’s chi-square, independent sample t-test, paired samples t-test, and a two- way repeated measures analysis of variance (ANOVA) was utilized in the analysis. Results: Bromazepam group had a significantly lowered ratio of systolic (SBP), diastolic (DBP), and mean arterial pressure (MAP) in the morning of the surgery (P<0.05). Bromazepam also reduced the ratio of SBP and MAP in theaters before anesthesia (P<0.05). A repeated measures ANOVA showed significant treatment effects for SBP and MAP but not DBP (P<0.001 for both). SBP, DBP, and MAP showed a significant time-treatment effect (P<0.001, 0.019, and<0.001, respectively). Conclusions: Oral bromazepam (anxiolytic) aids in the regulation of blood pressure in individuals with well-managed hypertension and in healthy patients having total hip arthroplasty without apparent adverse effects related to the medication. This could potentially reduce the number of uncontrolled hypertension-related surgery delays and patients on the surgical waiting list.

A new era in the treatment of kidney diseases: NLRP3 inflammasome and cytokine-targeted therapies.

The kidneys are crucial for filtering blood, managing overall body water, electrolyte, and acid-base balance, and regulating blood pressure. They remove metabolic waste products, toxins, and drugs. In addition, they limit inflammation by clearing cytokines and reduce immune cell activation by removing bacterial components. Dendritic cells (DCs) in the kidney maintain peripheral tolerance. About 85% of filtered water is reabsorbed by the proximal tubule, exposing distal nephron cells to high concentrations of low molecular weight antigens. These antigens are captured by DCs, helping to inactivate potentially autoreactive T cells and maintain tolerance to circulating antigens. In kidney failure, immune function is severely compromised due to the retention of toxins and cytokines, which activate immune cells and increase systemic inflammation. The kidneys are also vulnerable to immune-mediated diseases. Loss of immune homeostasis, characterized by over- or under-activity of the immune response, can adversely affect kidney function. With advances in immunology and cellular biology, biologic therapies targeting various pathways involved in the pathophysiology of kidney diseases are being developed. In this review, the immunologic aspects of kidney diseases and focus on cytokine-based therapies that may hold promise for the treatment of kidney diseases in the future will be presented.

Low-dose sufentanil does not affect tolerance to LBNP-induced central hypovolemia or blood pressure responses during a cold pressor test.

Hemorrhage is a leading cause of death in the prehospital setting. Since trauma-induced pain often accompanies a hemorrhagic insult, the administered pain medication must not interfere with critical autonomic regulation of arterial blood pressure and vital organ perfusion. The purpose of this study was to test two unrelated hypotheses: 1) sublingual sufentanil (Dsuvia) impairs tolerance to progressive central hypovolemia and 2) sublingual sufentanil attenuates pain sensation and the accompanying cardiovascular responses to a noxious stimulus. Twenty-nine adults participated in this double-blinded, randomized, crossover, placebo-controlled trial. After sublingual administration of sufentanil (30 μg) or placebo, participants completed a progressive lower-body negative pressure (LBNP) challenge to tolerance (aim 1). After a recovery period, participants completed a cold pressor test (CPT; aim 2). Addressing the first aim, tolerance to LBNP was not different between trials (P = 0.495). Decreases in systolic blood pressure from baseline to the end of LBNP also did not differ between trials (time P < 0.001, trial P = 0.477, interaction P = 0.587). Finally, increases in heart rate from baseline to the end of LBNP did not differ between trials (time P < 0.001, trial P = 0.626, interaction P = 0.424). Addressing the second aim, sufentanil attenuated perceived pain (P < 0.001) in response to the CPT, though the magnitude of the change in mean blood pressure during the CPT (P = 0.078) was not different between trials. These data demonstrate that sublingual sufentanil does not impair tolerance to progressive central hypovolemia. Additionally, sublingual sufentanil attenuates perceived pain, but not the accompanying mean blood pressure responses to the CPT.NEW & NOTEWORTHY Addressing two unique aims, we observed that sublingual sufentanil administration does not impair tolerance or cardiovascular responses to lower-body negative pressure (LBNP)-induced progressive central hypovolemia. Second, despite pain perception being reduced, sublingual sufentanil did not attenuate mean blood pressure responses to a cold pressor test (CPT).

Relationship between autonomic and peripheral neuropathies and cardiovascular outcomes in diabetes

This review explores the complex relationship between diabetic neuropathy and cardiovascular disease (CVD). Neuropathy, a common complication of type 1 and type 2 diabetes, is divided into autonomic and peripheral types, each impacting cardiovascular health. Cardiovascular autonomic neuropathy, a form of autonomic neuropathy, is associated with various CVD complications, including arrhythmias, impaired nocturnal blood pressure regulation, and increased mortality. The prevalence of cardiovascular autonomic neuropathy varies depending on the type and duration of diabetes and is influenced by factors like glycemic control and metabolic stress. Peripheral polyneuropathy, which is often linked to diabetic foot disease, is also correlated with elevated CVD risk; research suggests shared pathophysiological mechanisms between peripheral neuropathy and cardiovascular conditions. Screening for neuropathies using tools like the Michigan Neuropathy Screening Instrument and heart rate variability analyses can facilitate early detection of CVD risk. Additionally, emerging technologies, like deep learning models, have demonstrated promise in detecting early cardiovascular patterns associated with autonomic neuropathy through electrocardiogram analysis. These findings underscore the value of integrating novel diagnostic approaches for early intervention. As CVD represents a leading cause of death among patients with diabetes, this article emphasizes the need for thorough assessment and proactive management of neuropathy to mitigate cardiovascular risk. The review recommends a multidisciplinary approach to diabetes care, including early screening, accurate risk stratification, and targeted therapeutic strategies to prevent or slow the progression of CVD in patients with autonomic and peripheral neuropathies. Further research is warranted to clarify the optimal intervention strategies for reducing CVD risk in these populations.

Mineralocorticoid receptor blockage in kidney transplantation: too much of a good thing or not?

Although, kidney transplantation (KT) is the best treatment option for patients with end-stage kidney disease, long-term complications including chronic kidney allograft disease (CKAD) and major adverse cardiovascular events (MACE) are common. To decrease these complications new therapeutic options are necessary. Mineralocorticoid receptor antagonists (MRAs) are one of the promising drugs in this context. In the general population, MRAs had favorable effects on blood pressure regulation, MACE, proteinuria and progression of chronic kidney disease. In the context of KT, there are limited studies showing beneficial effects such as reducing proteinuria and oxidative stress. In this review, we performed a narrative review to assess the use and impact of MRAs in kidney transplant recipients. We found that in KTRs, MRAs are safe and they have favorable or neutral impact on blood pressure, glomerular filtration rate, urinary protein/albumin excretion, and oxidative stress. No data was found regarding major cardiovascular adverse events.

Angiotensin II as a linking factor in cardiovascular disease enhanced cancer growth

Abstract Introduction Several publications have demonstrated that cardiovascular diseases (CVD) promote tumor growth in mouse models of breast, lung, and colon cancer, suggesting a causal relationship between both diseases. Cancer and CVD share several risk factors and pathophysiological mechanisms, including inflammation, oxidative stress, neurohormonal activation, and immune system dysfunction that combined could explain why patients with CVD are prone to develop cancer. Recent reports also suggest a link between hypertension and lung cancer, and between cardiac hypertrophy and breast cancer. Angiotensin II (ANGII) is a hormone involved in blood pressure regulation, vascular hemostasis and hypertrophy development. Moreover, ANGII is cancerogenic by increasing proliferation of several cancer cell types. Hence, ANGII could be a link in CVD-induced enhancement of cancer growth. Here, we investigated whether ANGII treatment, and subsequent hypertension and cardiac hypertrophy, could promote cancer growth and metastasis. Methods ANGII (2000ng.kg-1.min-1, 4w) was administered to 10w old C57B6/J mice using subcutaneous osmotic minipumps. After 3w, 5*10^5 Lewis lung carcinoma (LLC) cells or 2*10^5 MC38 colon cancer cells were injected onto the right flank of the mice. Tumor growth was monitored over 21d using a digital caliper. Tumor volume was calculated using the following formula: Length × width² × 0.5 On day 22, mice were sacrificed for further post-mortem analysis. Cardiac echography was performed after 3w of ANGII treatment and before sacrifice to assess cardiac function (data not shown). To assess the formation of cardiac fibrosis trichrome staining’s were performed. In addition, the effect of ANGII on LLC metastasis was investigated. Mice were treated with ANGII as described above. LLC cells, 2*10^6, were injected intravenously (i.v.). Mice were sacrificed 21d after cell injection. Metastatic growth was visualized and quantified by organ weighing and H&amp;E staining. Results LLC tumor growth was significantly increased by ANGII treatment. In addition, post-mortem tumor weight was increased (0.62 ± 0.05 g control vs. 1.17 ± 0.24 g ANGII). Furthermore, we found lung weight increased in the ANGII-treated group injected i.v. with LLC cells, indicating an increase in metastatic growth (0.41 ± 0.08 g control vs. 0.57 ± 0.04 g ANGII). Interestingly, MC38 tumor growth decreased in the ANGII treated group as portrayed by the tumor weight (0.42 ± 0.06 g control vs. 0.19 ± 0.05 g ANGII). Figure 1 shows the tumor growth over time and tumor volume, weight post-mortem. Conclusion Our data suggest a role for ANGII in CVD-enhanced cancer growth, but also that this effect is not universal, illustrated by a differential effect of ANGII on distinct cancer types. Although further investigation is required to unravel the role of ANGII, screening cancer patients with CVD comorbidities for ANGII involvement might be warranted.

Causal Associations Between the Gut Microbiota and Hypertension-Related Traits Through Mendelian Randomization: A Cross-Sectional Cohort Study.

Previous studies have suggested a link between the gut microbiome and hypertension-related traits like blood pressure. However, these reports are often limited by weak causal evidence. This study investigates the potential causal association between gut microbiota and hypertension-related traits using Mendelian randomization with summary data from genome-wide association studies. The inverse-variance weighted method revealed that the Clostridium innocuum group (Odds ratio [OR]: 1.0047, 95% confidence interval [CI]: 1.0004-1.0090, p=0.0336), Eubacterium fissicatena group (OR: 1.0047, 95% CI: 1.0005-1.0088, p=0.0266), Lachnospiraceae FCS020 group (OR: 1.0063, 95% CI: 1.0004-1.0122, p=0.0361), and Olsenella (OR: 1.0044, 95% CI: 1.0001-1.0088, p=0.0430) were associated with an increased risk of hypertension. Conversely, Flavonifractor (OR: 0.9901, 95% CI: 0.9821-0.9982, p=0.0166), Parabacteroides (OR: 0.9874, 95% CI: 0.9776-0.9972, p=0.0121), and Senegalimassilia (OR: 0.9907, 95% CI: 0.9842-0.9974, p=0.0063) were associated with a decreased risk of hypertension. External validation with the Guangdong Gut Microbiome Project confirmed a negative correlation between Parabacteroides and hypertension, potentially through metabolic pathways. These findings provide further evidence supporting the hypothesis that microbes and their metabolites play a role in blood pressure regulation.

Effect of selective renal denervation guided by renal nerve stimulation on atrial remodeling

Abstract Background The renal nerves play a crucial role in regulating blood pressure (BP), and the parasympathetic nervous has been confirmed as one of the components of the renal nerves, with close connections to the central solitary nucleus. Renal nerve stimulation (RNS) can activate not only the sympathetic nerves, leading to an elevation in BP, but also the parasympathetic nerves, resulting in a reduction in BP. Multiple clinical studies have demonstrated that compared to pulmonary vein isolation (PVI), renal denervation (RDN) combined with PVI significantly increased the likelihood of freedom from atrial fibrillation, but its mechanism remains unclear. Purpose Exploring the effects of renal sympathetic denervation and renal parasympathetic denervation on atrial neural remodeling and structural remodeling from a histological perspective of atrial myocardium. Methods 24 adult healthy Kunming dogs were randomly divided into three groups: (1) RNS-guided reduced BP response sites ablation (RRA group, n=8), (2) RNS-guided elevated BP response sites ablation (ERA group, n=8), and (3) RNS only, no ablation (RSC group, n=8). Left atrial samples were obtained after a 4-week follow-up period. Results Compared to the RSC group, the ERA group showed a significant decrease in tyrosine hydroxylase (TH), while the RRA group showed a significant decrease in choline acetyltransferase (CHAT) and muscarinic acetylcholine receptor 2 (CM2) (Fig. 1A-1C). Histological results indicated that compared to the RSC group, the ERA group exhibited orderly arrangement of myocardial cells, with a significant reduction in the degree of mitochondrial swelling and a decrease in average myocardial cell area. In contrast, the RRA group showed disordered arrangement of myocardial cells, with some myofibril dissolution, noticeable swelling of cell nuclei and mitochondria, and an increase in average myocardial cell area (Fig. 1D). Further evaluation of left atrial fibrosis degree revealed that compared to the RSC group, the ERA group showed a significant decrease in Collagen I, with a reduction in interstitial fibrosis degree, while the RRA group showed a significant increase in Collagen I expression, with an increase in myocardial interstitial fibrosis degree (Fig.2). Conclusion Renal sympathetic denervation can reduce atrial sympathetic nerve, improve atrial macrostructure, ultrastructure, and fibrosis levels, which may be one of the reasons why RDN combined with PVI is more effective in maintaining sinus rhythm compared to PVI. Renal parasympathetic denervation can decrease atrial parasympathetic nerve, leading to deterioration of atrial tissue structure and exacerbation of fibrosis. This emphasizes the importance of electrical stimulation guidance during the RDN procedure to avoid "side effects" caused by renal parasympathetic nerves ablation.Figure 1Figure 2

Physiological characteristics of blood pressure responses after combined exercise in elderly hypertensive patients: a systematic review and meta-analysis

ObjectiveThe aim of this investigation is to explore the efficacy of combined exercise in elderly patients with hypertension. Moreover, we aim to delve into the underlying mechanisms governing blood pressure regulation, with the objective of promoting the adoption of this exercise regimen among elderly hypertensive individuals.MethodsIn our study, we conducted a thorough search across multiple databases, including PubMed, Web of Science, Cochrane Library, Embase, and Scopus. This extensive search resulted in the preliminary screening of 2,347 articles. Among these, 9 studies were carefully selected for an in-depth analysis. For our meta-analysis, we employed Review Manager 5.3 and Stata 15.0, enabling us to perform detailed subgroup analyses and assess the possibility of publication bias.ResultsIn comparison to the control group (n = 194), individuals enrolled in the combined exercise group (n = 200) exhibited a notable decrease in both resting systolic blood pressure (SBP) [weighted mean difference (WMD) = −11.17 mm Hg, 95% confidence interval (CI) (−17.13, −5.22), Z = 3.68, P &amp;lt; 0.05] and diastolic blood pressure (DBP) [WMD = −5.93 mm Hg, 95% CI (−9.24, −2.61), Z = 3.51, P &amp;lt; 0.05]. Nonetheless, no statistically significant alteration was observed in pulse pressure (PP) [WMD = −9.05 mm Hg, 95% CI (−22.65, 4.55), Z = 1.3, P = 0.192]. Further subgroup analyses elucidated that combined exercise regimens, characterized by aerobic training intensities below 85% of HRmax, durations of up to 12 weeks, weekly frequencies of either ≥3 or &amp;lt;3 sessions, total session times under 60 min, and a sequence of aerobic exercise followed by resistance training (AE-RT), were particularly effective in enhancing SBP and DBP among elderly patients with hypertension. Additionally, regular engagement in combined exercise led to significant improvements in SBP and DBP across individuals aged 60–70, those older than 70 years, and regardless of whether participants were using antihypertensive medications or not.ConclusionCombined exercise serves as an efficacious adjunctive therapy for reducing blood pressure among elderly individuals with hypertension, exerting beneficial influences on multiple physiological mechanisms pertinent to blood pressure regulation. Moreover, the integration of aerobic exercise with resistance training presents a more varied training program, thereby eliciting wider-ranging positive effects on both the physical and mental well-being of elderly patients afflicted with hypertension.

ACE Inhibitors and Angiotensin Receptor Blockers for the Primary and Secondary Prevention of Cardiovascular Outcomes: Recommendations from the 2024 Egyptian Cardiology Expert Consensus in Collaboration with the CVREP Foundation.

The renin-angiotensin-aldosterone system (RAAS) plays a pivotal role in regulating blood pressure (BP), with dysregulation of RAAS resulting in hypertension and potentially heart failure (HF), myocardial infarction (MI), cardio-renal syndrome, and stroke. RAAS inhibitors, such as angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs), have advantages beyond BP control. However, differences between these two drug classes need to be considered when choosing a therapy for preventing cardiovascular events. A panel of 36 Egyptian cardiologists developed consensus statements on RAAS inhibitors for primary and secondary prevention of cardiovascular outcomes and stroke, using a modified three-step Delphi process. The consensus statements highlight the importance of effective BP control and the role of RAAS blockade for prevention and management of various cardiovascular diseases. ACEis and ARBs differ in their mode of action and, thus, clinical effects. On the basis of available evidence, the consensus group recommended the following: ACEis should be considered as first choice (in preference to ARBs) to reduce the risk of MI, for primary prevention of HF, and for secondary prevention of stroke. ACEis and ARBs show equivalent efficacy for the primary prevention of stroke. Evidence also favors the preferential use of ACEis in patients with type 2 diabetes, for BP control, for the primary prevention of diabetic kidney disease, and to reduce the risk of major cardiovascular and renal outcomes. Treatment with an ACEi should be started within 24 h of ST segment elevation MI (and continued long term) in patients with HF, left ventricular systolic dysfunction, and/or diabetes. Angiotensin receptor/neprilysin inhibitors (ARNIs) are the first choice for patients with HF and reduced ejection fraction, with ACEis being the second choice in this group. ARBs are indicated as alternatives in patients who cannot tolerate ACEis. ACEis may be associated with cough development, but the incidence tends to be overestimated, and the risk can be reduced by use of a lipophilic ACEi or combining the ACEi with a calcium channel blocker. RAAS blockade is an essential component of hypertension therapy; however, the protective effects provided by ACEis are superior to those of ARBs. Therefore, an ACEi is indicated in almost all cases, unless not tolerated.

Renal Inflammation, Oxidative Stress, and Metabolic Abnormalities During the Initial Stages of Hypertension in Spontaneously Hypertensive Rats

Background: Hypertension is a major cause of mortality worldwide. The kidneys play a crucial role in regulating blood pressure and fluid volume. The relationship between the kidneys and hypertension is complex, involving factors such as the renin–angiotensin system, oxidative stress, and inflammation. This study aims to assess the levels of inflammatory markers, oxidative stress, and metabolic factors in the kidneys, focusing on their potential role in early renal damage and their association with the development of hypertension. Methods: This study was designed to compare the levels of selected inflammatory markers, e.g., interleukins, tumor necrosis factor-α (TNF-α), transforming growth factor, and serine/threonine-protein (mTOR); oxidative stress markers such as malondialdehyde, sulfhydryl group, and glucose (GLC); and metabolic markers among other enzymes, such as alanine transaminase (ALT), aspartate transaminase (AST), hexokinase II (HK-II), and hypoxia-inducible factor-1α (HIF-1α), as well as creatinine in the kidneys of spontaneously hypertensive rats (SHR/NCrl, n = 12) and Wistar Kyoto rats (WKY/NCrl, n = 12). Both juvenile (5 weeks old) and maturing (10 weeks old) specimens were examined using spectrophotometric methods, e.g., ELISA. Results: Juvenile SHRs exhibited reduced renal levels of all studied cytokines and chemokines, with lower oxidative stress and deficits in the mTOR and HK-II levels compared to the age-matched WKYs. Maturing SHRs showed increased renal levels of interleukin-1β (IL-1β), IL-6, IL-18, and TNF-α, alongside elevated carbonyl stress and increased HIF-1α as opposed to their control peers. The levels of all other studied markers were normalized in these animals, except for ALT (increased), ALP, and GLC (both reduced). Conclusions: This study underscores the significant impact of inflammatory, oxidative stress, and metabolic marker changes on renal function. Juvenile SHRs display lower marker levels, indicating an immature immune response and potential subclinical kidney damage that may contribute to hypertension development. In contrast, mature SHRs exhibit chronic inflammation, oxidative dysregulation, and metabolic disturbances, suggesting cellular damage. These changes create a feedback loop that worsens kidney function and accelerates hypertension progression, highlighting the kidneys’ crucial role in both initiating and exacerbating this condition.

Modulation of blood pressure by dietary potassium and sodium: Sex differences and modeling analysis.

High Na+ intake has been linked to elevations in blood pressure, whereas K+ has the opposite effect. The underlying mechanisms involve complex interactions among renal function, fluid volume, fluid-regulatory hormones, the vasculature, cardiac function, and the autonomic nervous system. These mechanisms are likely moderated by sex, given the known sex differences in blood pressure regulation and the higher prevalence of hypertension in men. The source of these observed sex differences may be traced to organ and tissue levels, given that kidney function, intrarenal renin-angiotensin system components, renal sympathetic nervous activity, and nitric oxide bioavailability all exhibit sex differences. To assess the functional impact of each of these sex differences, we developed sex-specific computational models to simulate whole-body Na+, K+, and fluid homeostasis, and the effects on blood pressure. The models describe the interactions among the renal system, cardiovascular system, gastrointestinal system, renal sympathetic nervous system, and renin-angiotensin-aldosterone system. Model simulations suggest that women's attenuated blood pressure response to hypertensive stimuli, including high Na+ intake, may be largely attributable to the female renal transporter abundance pattern. Additionally, we investigated the causal link between high K+ intake and blood pressure reduction. The models simulate renal response to high K+ intake, including the immediate gastrointestinal feedforward signals to the kidneys to increase K+ excretion, and the longer-term response to decrease proximal fractional Na+ reabsorption and distal K+ reabsorption. With these assumptions, simulations of high K+ intake yielded kaliuresis, natriuresis, and a substantial reduction in blood pressure, even when combined with high Na+ intake.

The FSGS protein actinin-4 (ACTN4) interacts with NKCC2 to regulate Thick Ascending Limb (TAL) NaCl reabsorption.

In the kidney, the thick Ascending Limb (TAL) of the loop of Henle is crucial for NaCl homeostasis and blood pressure regulation. In animal models of salt-sensitive hypertension, NaCl reabsorption via the apical Na+/K+/2Cl cotransporter (NKCC2) is abnormally increased in the TAL. We showed that NaCl reabsorption is controlled by the presence of NKCC2 at the apical surface of TALs. However, the molecular mechanisms that maintain the steady-state levels of NKCC2 at the apical surface are not clearly understood. Here, we report that NKCC2 interacts with the F-actin cross-linking protein actinin-4 (ACTN4). We find that ACTN4 is expressed in TALs by Western blot and immunofluorescence microscopy. ACTN4 immunoprecipitated with NKCC2 and recombinant GST-ACTN4 pulled down NKCC2 from TAL lysates. ACTN4 is involved in endocytosis in other cells. Therefore, we hypothesized that ACTN4 binds apical NKCC2 and regulates its trafficking. To study this, we silenced ACTN4 in vivo via shRNA or CRISPR/Cas9 system to decrease ACTN4 expression in TALs. We observed that silencing ACTN4 in vivo via shRNA or CRISPR/Cas9 system increased the amount NKCC2 at the apical surface of TALs. Bumetanide-induced diuresis and natriuresis were enhanced by 35% after silencing of ACTN4 in vivo (AV-NKCC2-Cas9: 3841±709 vs AAV-gRNA-ACTN4: 5546±622 µmols Na/8h, n=5, p<0.05). We conclude that ACTN4, binds NKCC2 to regulate its surface expression. Selective depletion of ACTN4 in TALs using shRNA or CRISPR/Cas9 enhances surface NKCC2 and TAL NaCl reabsorption, indicating that regulation of the ACTN4-NKCC2 interaction is important for renal NaCl reabsorption and could be related to hypertension.

Salt Responsive Gut Microbiota Induces Sex Specific Blood Pressure Changes.

Tryptophan metabolism is important in blood pressure regulation. The tryptophan-indole pathway is exclusively mediated by the gut microbiota. ACE2 (angiotensin-converting enzyme 2) participates in tryptophan absorption, and a lack of ACE2 leads to changes in the gut microbiota. The gut microbiota has been recognized as a regulator of blood pressure. Furthermore, there is ample evidence for sex differences in the gut microbiota. However, it is unclear whether such sex differences impact blood pressure differentially through the tryptophan-indole pathway. To study the sex-specific mechanisms of gut microbiota-mediated tryptophan-indole pathway in hypertension, we generated a novel rat model with Clustered Regularly Interspaced Short Palindromic Repeats/Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats-associated protein 9)-targeted deletion of Ace2 in the Dahl salt-sensitive rat. Cecal microbiota transfers from donors of both sexes to female S recipients were performed. Also, Dahl salt-sensitive rats of both sexes were orally gavaged with indole to investigate blood pressure response. The female gut microbiota and its tryptophan-indole pathway exhibited greater buffering capacity when exposed to tryptophan, due to Ace2 deficiency, and salt. In contrast, the male gut microbiota and its tryptophan-indole pathway were more vulnerable. Female rats with male cecal microbiota responded to salt with a higher blood pressure increase. Indole, a tryptophan-derived metabolite produced by gut bacteria, increased blood pressure in male but not in female rats. Moreover, salt altered host-mediated tryptophan metabolism, characterized by reduced serum serotonin of both sexes and higher levels of kynurenine derivatives in the females. We uncovered a novel sex-specific mechanism in the gut microbiota-mediated tryptophan-indole pathway in blood pressure regulation. Salt tipped the tryptophan metabolism between the host and gut microbiota in a sex-dependent manner. Our study provides evidence for a novel concept that gut microbiota and its metabolism play sex-specific roles in the development of salt-sensitive hypertension.

20-HETE, Blood Pressure, and Vascular Stiffness in Young Adults.

Cytochrome-P450 eicosanoids from arachidonic acid, including vasodilator epoxyeicosatrienoic acids (EETs) and the vasoconstrictor 20-HETE, are important in regulating blood pressure, vascular tone, and cardiac and renal function. This study examined plasma 20-HETE and EETs in relation to blood pressure and vascular stiffness in a cohort of 1054 community-dwelling young adults from the Raine Study at 27 years. Plasma 20-HETE, EETs, and their hydroxylated products were measured by liquid chromatography-tandem mass spectrometry. Pulse wave velocity and aortic distensibility were measured to assess vascular stiffness. Sex differences were assessed using univariate analysis. Multiple regression models assessed the relationship between 20-HETE and systolic blood pressure (SBP) and measures of vascular stiffness. The regression model for SBP showed a positive relationship with plasma 20-HETE (β, 0.092; P<0.0001), after adjusting for sex (P<0.0001), body mass index (P<0.0001), (ln)triglycerides (P<0.0001), and (ln)HOMA-IR (P=0.015), and accounted for 29% of the variance in SBP. 20-HETE was positively related to pulse wave velocity (β, 0.059; P=0.021); after adjusting for sex (P<0.0001), SBP (P<0.0001), (ln)triglycerides (P=0.014), (ln)HOMA-IR (P=0.0001), (ln)high-sensitivity C-reactive protein (P=0.005), and age (P=0.002), the model accounted for 34% of the variance in pulse wave velocity. 20-HETE was inversely associated with aortic distensibility (β, -0.051; P=0.029), independent of sex (P<0.0001), SBP (P<0.0001), and (ln)HOMA-IR (P<0.0001); the model accounted for 25% of the variance in aortic distensibility. Plasma EETs were not significant predictors of SBP or vascular stiffness. In young adults, 20-HETE may play a fundamental role in regulating blood pressure and vascular stiffness independent of numerous cardiometabolic risk factors and cytochrome 450-derived EETs. URL: https://www.anzctr.org.au; Unique identifier: CTRN12617001599369.

A systematic review of lithium biology and pharmacology and toxicological evaluation of new organic lithium salts

Objective: to systematize scientific data on biomedical studies investigating trace element lithium over the past 70 years; evaluate toxic properties of lithium ascorbate (LiAsc) as an important promising candidate molecule.Material and methods. An analysis of 49,959 publications on lithium biomedical research retrieved from PubMed/MEDLINE database was carried out using modern data mining methods developed within the framework of topological approach to recognizing (Yu.I. Zhuravlev scientific school). Publications found by experts and not indexed in PubMed/MEDLINE were used in discussing the results of a systematic analysis of publications array retrieved from PubMed/MEDLINE. An experimental study of chronic 180 day-long LiAsc (at doses of 5, 50 and 150 mg/kg) toxicity was performed on 36 “Soviet chinchilla” rabbits by assessing local irritant action. Intoxication clinical picture, body weight dynamics, water and food intake as well as physiological, hematological and biochemical parameters were analyzed.Results. Classification and systematization of all currently available publications on lithium biology and medicine were performed. It was shown that pharmacological applications of lithium salts in mental disorders as well as lithium effects on simple sugars metabolism, lipid metabolism, blood pressure regulation, hematopoiesis, inflammation and tumor growth inhibition, neurotransmitter homeostasis, neurotrophic and neuroprotective molecular mechanisms as well as homeostasis of other electrolytes comprised promising fields of lithium drug research. The prospects for using organic lithium salts, particularly LiAsc, for various therapeutic goals were also discussed. 180-day-long oral administration of LiAsc at doses of 5, 50, 150 mg/kg resulted in no macroscopic signs of local inflammatory reaction while examining its local irritant effect.Conclusion. The lithium-ion effect on neurotransmitters promotes neuroprotection and reduces a risk of addiction. The antihypertensive, antiatherosclerotic, antidiabetic, antitumor and neurotrophic effects related to organic lithium salts may be beneficial in various therapeutic applications.

The effect of cpap therapy on blood pressure in the mild obstructive sleep apnea population

This retrospective study uniquely focused on the effects of continuous positive airway pressure (CPAP) on blood pressure in patients with mild obstructive sleep apnea (OSA), a condition characterized by intermittent upper airway collapse. OSA is a well-established risk factor for hypertension, with positive airway pressure (PAP) therapy being the most common treatment. While substantial evidence supports PAP therapy in moderate and severe OSA, the impact of CPAP on mild OSA, which accounts for 50%-70% of all cases, remains underexplored. The primary objective of this study was to investigate whether CPAP therapy, particularly the degree of adherence to treatment, has a measurable impact on blood pressure regulation in patients with mild OSA. Specifically, this research aimed to evaluate whether consistent CPAP use could lower systolic and diastolic blood pressure and assess how varying levels of adherence influence these outcomes. Participants were stratified into two groups based on CPAP adherence: Group A (n = 45) included those who used CPAP for four or more hours per night on at least 70% of nights, while Group B (n = 15) consisted of those with less than four hours of CPAP use per night on 70% of nights. Interestingly, greater systolic and diastolic blood pressure reductions were observed in Group B, suggesting that lower CPAP adherence may still contribute to significant cardiovascular improvements. These findings offer new insights into the management of blood pressure in patients with mild OSA and the role of CPAP adherence.

Nitric Oxide: Structure, Pathophysiology and Clinical Significance

Hypertension is the most important modifiable risk factor and, if treated, leads to a reduction in cardiovascular diseases and mortality. A recent perspective emphasizes the central role of nitric oxide bioavailability in the maintenance of healthy vasculature and the regulation of blood pressure. The molecule nitric oxide is very complex with far-reaching implications concerning cardiovascular well-being and pathology. Synthesis of nitric oxide as well as signaling cascades and their regulation thus stands as a critical process in acquiring an understanding regarding its involvement under physiological as well as pathological conditions. With the rapid pace at which NO research is evolving, there are significant gaps in our knowledge that must be filled in if we are ever to take full advantage of its therapeutic potential. Nitric oxide is also considered to be a very important molecule involved in the defense of hypertension through its effects on endothelial function and vascular homeostasis. This review will summarize the current state of knowledge regarding the relationship between NO and hypertension and will attempt to identify those areas where significant lacunae exist and where further research would be appropriate. In addition, focus is directed toward the structure and clinical relevance of NO, describing its functions in endothelial activity, cardiovascular health, and any possible clinical utility.

Combretum micranthum G. Don (Combretaceae): Its physiological effects on hydro-electrolyte metabolism, renal tubular function and blood pressure

BackgroundHydro-electrolyte balance is necessary to maintain body homeostasis and blood pressure values within narrow limits. This is accomplished, in part, by renal responses. We conducted this study to determine the effects of Combretum micranthum on hydro-electrolyte metabolism, renal function and arterial blood pressure. Subjects and methodsWe conducted a pilot study including 40 subjects: 10 control subjects, 10 subjects under Combretum micranthum G. Don (400 mg/day), 10 subjects under furosemide (120 mg/day), and 10 subjects under spironolactone (50 mg/day).Anthropobiometric, cardiovascular parameters and the body composition were collected from each subject. Blood and 24-hour urine samples were collected for biological tests. ResultsAt baseline, clinical and biological parameters were comparable for all groups. Consumers of combretum micranthum had a significant decrease in global body fat percentage (−1.63 %; p = 0.045). In the group of combretum micranthum consumers, the body water mass (BWM) is significantly evolved in the direction of an increase (4.37; p = 0.023) and similar to what was observed in the group of subjects treated with spironolactone (0.67; p = 0.042). Consumption of combretum micranthum showed a marked reduction in hypertension indices (systolic blood pressure, diastolic blood pressure and heart rate) identical to that induced by consumption of furosemide or spironolactone. The consumption of combretum micranthum resulted in a significant reduction in kaliemia (−1.07; p < 0.0001) and without any notable effect on natremia (p = 0.119) and chloremia (p = 0.708). In contrast, furosemide and spironolactone caused a significant decrease in natremia (respectivly, −0.80; p = 0.022 and −0.50; p = 0.009). In the combretum micrathum group, the kaliuresis and the chloruresis were significantly increased (respectively, 373.9; p = 0.005 and 441.3; p = 0.028), interestingly, we found a remarkable decrease in natriuresis (−193.3; p = 0.074). In the group of furosemide consumers, the kaliuresis and the chloruresis were significantly increased (respectively, 380.24; p = 0.013 and 425.5; p = 0.013), but with a tendency to increase natriuresis. In the group of subjects taking spironolactone, the urinary concentrations of the three electrolytes studied (natriuresis, kaliuresis and chloruresis) was increased significantly (respectively, 357.5; p = 0.037 and 222.5; p = 0.005 and 563.4; p = 0.007). ConclusionCombretum micranthum would have constituents involved in the maintenance of hydro-electrolyte homeostasis and in the regulation of blood pressure through the involvement of several mechanisms, especially at the renal level. These actions would be attributable to its polyphenolic components. A broader study is needed to better understand the physiological mechanisms underlying these effects.

Genomic Exploration of Essential Hypertension in African-Brazilian Quilombo Populations: A Comprehensive Approach with Pedigree Analysis and Family-Based Association Studies.

Essential Hypertension (EH) is a global health issue. Despite extensive research, much of EH heritability remains unexplained. We investigated the genetic basis of EH in African-derived individuals from partially isolated quilombo populations in Vale do Ribeira (SP-Brazil). Samples from 431 individuals (167 affected, 261 unaffected, 3 unknown) were genotyped using a 650k SNP array. Estimated global ancestry proportions were 47% African, 36% European, and 16% Native American. We constructed six pedigrees using additional data from 673 individuals and created three non-overlapping SNP subpanels. We phased haplotypes and performed local ancestry analysis to account for admixture. Genome-wide linkage analysis (GWLA) and fine-mapping via family-based association studies (FBAS) were conducted, prioritizing EH-associated genes through systematic approach involving databases like PubMed, ClinVar, and GWAS Catalog. Linkage analysis identified 22 regions of interest (ROIs) with LOD scores ranging 1.45-3.03, encompassing 2363 genes. Fine-mapping (FBAS) identified 60 EH-related candidate genes and 117 suggestive/significant variants. Among these, 14 genes, including PHGDH , S100A10 , MFN2 , and RYR2 , were strongly related to hypertension harboring 29 suggestive/significant SNPs. Through a complementary approach - combining admixture-adjusted GWLA based on Markov chain Monte Carlo methods, FBAS on known and imputed data, and gene prioritizing - new loci, variants, and candidate genes were identified. These findings provide targets for future research, replication in other populations, facilitate personalized treatments, and improve public health towards African-derived underrepresented populations. Limitations include restricted SNP coverage, self-reported pedigree data, and lack of available EH genomic studies on admixed populations for independent validation, despite the performed genetic correlation analyses using summary statistics.