Blood Pressure Lowering Effect Research Articles

Esaxerenone: blood pressure reduction and cardiorenal protection without reflex sympathetic activation in salt-loaded stroke-prone spontaneously hypertensive rats.

Mineralocorticoid receptor (MR) is involved in the mechanisms of blood pressure elevation, organ fibrosis, and inflammation. MR antagonists have been used in patients with hypertension, heart failure, or chronic kidney disease. Esaxerenone, a recently approved MR blocker with a nonsteroidal structure, has demonstrated a strong blood pressure-lowering effect. However, blood pressure reduction may lead to sympathetic activation through the baroreflex. The effect of esaxerenone on the sympathetic nervous system remains unclear. We investigated the effect of esaxerenone on organ damage and the sympathetic nervous system in salt-loaded stroke-prone spontaneously hypertensive rats (SHRSP), a well-established model of essential hypertension with sympathoexcitation and organ damage. Three-week administration of esaxerenone or hydralazine successfully attenuated the blood pressure elevation. Both esaxerenone and hydralazine comparably suppressed left ventricular hypertrophy and urinary albumin excretion. However, renal fibrosis and glomerular sclerosis were suppressed by esaxerenone but not hydralazine. Furthermore, plasma norepinephrine level, a parameter of systemic sympathetic activity, was significantly increased by hydralazine but not by esaxerenone. Consistent with these findings, the activity of the control centers of sympathetic nervous system, the parvocellular region of the paraventricular nucleus in the hypothalamus and the rostral ventrolateral medulla, was enhanced by hydralazine but remained unaffected by esaxerenone. These results suggest that esaxerenone effectively lowers blood pressure without inducing reflex sympathetic nervous system activation. Moreover, the organ-protective effects of esaxerenone appear to be partially independent of its blood pressure-lowering effect. In conclusion, esaxerenone demonstrates a blood pressure-lowering effect without concurrent sympathetic activation and exerts organ-protective effects in salt-loaded SHRSP. Esaxerenone has antihypertensive and cardiorenal protective effects without reflex sympathetic activation in salt-loaded stroke-prone spontaneously hypertensive rats.

Differing contributions of the gut microbiota to the blood pressure lowering effects induced by first-line antihypertensive drugs.

This study analyses whether first-line antihypertensive drugs ameliorate the dysbiosis state in hypertension, and to test if this modification contributes to their blood pressure (BP) lowering properties in a genetic model of neurogenic hypertension. Twenty-week-old male Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were untreated or treated with captopril, amlodipine or hydrochlorothiazide. A faecal microbiota transplantation (FMT) experiment was also performed by gavage of faecal content from donor SHR-treated groups to SHR recipients for 3 weeks. Faeces from SHR showed gut dysbiosis, characterized by lower acetate- and higher lactate-producing bacteria and lower strict anaerobic bacteria. All three drugs increased the anaerobic bacteria proportion, captopril and amlodipine restored the proportion of acetate-producing bacterial populations to WKY levels, whereas hydrochlorothiazide decreased butyrate-producing bacteria. Captopril and amlodipine decreased gut pathology and permeability and attenuated sympathetic drive in the gut. Both drugs decreased neuroinflammation and oxidative stress in the hypothalamic paraventricular nuclei. Hydrochlorothiazide was unable to reduce neuroinflammation, gut sympathetic tone and gut integrity. FMT from SHR-amlodipine to SHR decreased BP, ameliorated aortic endothelium-dependent relaxation to acetylcholine, lowered NADPH oxidase activity, aortic Th17 infiltration and reduced neuroinflammation, whereas FMT from SHR-hydrochlorothiazide did not have these effects. First-line antihypertensive drugs induced different modifications of gut integrity and gut dysbiosis in SHR, which result in no contribution of microbiota in the BP lowering effects of hydrochlorothiazide, whereas the vasculo-protective effect induced by amlodipine involves gut microbiota reshaping and gut-immune system communication.

TEN YEAR FOLLOW-UP OF PATIENTS WITH RESISTANT HYPERTENSION RANDOMIZED TO RENAL DENERVATION OR ANTIHYPERTENSIVE DRUG TREATMENT

Objective: Renal denervation (RDN) is a treatment option in resistant hypertension. The procedure is considered safe, although randomized trials only demonstrate a moderate blood pressure (BP) lowering effect, when considering medication adherence. Some observational studies describe reduction in BP several years after the procedure. The aim of the study was to describe long-term safety and potential benefits of RDN after ten years, compared to optimized drug treatment, measuring serum concentration of antihypertensive drugs to ensure adherence. Design and method: We report data from ten year follow-up of patients randomized to RDN (n=9) or drug adjustment (n=10). Initially the patients had treatment-resistant hypertension, defined as daytime systolic ambulatory BP >= 135 mmHg after witnessed intake (directly observed therapy, DOT) of >= 3 antihypertensive drugs including a diuretic and therefore considered as adherent. One year after RDN or drug adjustment, we optimized antihypertensive medication for all patients. Thereafter, patients received appropriate antihypertensive treatment in primary or secondary care, according to their BPs. Patients were informed of serum concentration measurements performed at the 7-year visit. At the 10-year visit, serum drug measurements before DOT and ambulatory BP measurement (ABPM) were used for evaluation of adherence. Antihypertensive agents were registered, glomerular filtration rate (eGFR) was estimated by the CKD-EPI formula using creatinine and Cystatin C, and renal arteries were examined by CT or MRI. Results: All living patients (n=18) attended the 10-year visit, now mean age 69 years, using 4±2 antihypertensive agents, with no difference between groups. Serum concentrations confirmed that all patients were adherent to reported medication. There were significant and similar BP reductions in both groups compared to baseline; daytime ABPM -22±15/9±8 mmHg in the RDN group, and -20±15/13±7 mmHg in the control group (figure). No patients developed renal artery stenosis. The decrease in eGFR was similar in both groups. Conclusions: To our knowledge this is the RCT with the longest follow-up supporting long-term safety of RDN in patients with resistant hypertension. Daytime ABPM improved during 10 years of follow-up, not explained by RDN, but due to adjustments in antihypertensive regimens and probably better adherence to medication.

Angiotensin-(1-7) Mas Receptors are Highly Colocalized to GABAergic Proopiomelanocortin Neurons in the Arcuate Nucleus of the Hypothalamus

Previous studies from our laboratory have shown that circulating levels of angiotensin (Ang)-(1-7), a protective hormone of the renin-angiotensin system, are greatly reduced in obese hypertensive mice. Additionally, restoration of this hormone reduces cardiovascular sympathetic tone and lowers blood pressure in this model suggesting a central mechanism of action. In support of this, our recent data show that the sympatho-inhibitory and blood pressure lowering effects of Ang-(1-7) involve activation of mas receptors (masR) within the arcuate nucleus of the hypothalamus (ARC). More specifically, we have found that masR are highly colocalized to proopiomelanocortin (POMC) neurons in the ARC. Due to the heterogeneous nature of POMC neuron subtypes, we wanted to explore the neurotransmitter phenotype of these POMCmasR neurons. We hypothesized that due to the blood pressure lowering effects of Ang-(1-7), POMCmasR are likely colocalized to inhibitory GABAergic neurons. To test this, we performed RNAscope in-situ hybridization in male C57Bl/6J mice after twelve weeks of either a 60% high fat diet (HFD) or matched control diet (n=12-18/group). We used RNAscope to colocalize expression of POMC, masR, and the vesicular GABA transporter, Vgat, mRNA transcripts within the ARC. Colocalization of POMCmasR and Vgat was quantified and percent-colocalization compared between control and HFD groups. We found that POMCmasR are highly colocalized with the GABAergic marker, Vgat, to a similar extent in control and HFD groups (84±4 vs. 90±2% of neurons, respectively; p=0.294 unpaired t-test). The population of POMC neurons that did not express masR also did not colocalize with Vgat. As an initial step to determine if masR modulates GABAergic signaling in the ARC, we assessed gene expression of glutamate decarboxylase 2 (Gad2; a GABA synthetic enzyme) in the ARC following chronic six-week treatment with systemic Ang-(1-7) versus saline infusion in male mice fed a control diet versus HFD (n=9-13/group). We found that Ang-(1-7) increases ARC Gad2 mRNA in HFD mice (1.03±0.09 control diet vs. 0.93±0.07 HFD vs. 1.23±0.07 HFD plus Ang-(1-7); p=0.023 one-way ANOVA). Supporting specificity of these actions, Ang-(1-7) did not alter POMC mRNA in the ARC. These overall data suggest that masR primarily localize to GABA-expressing POMC neurons in the ARC, and Ang-(1-7) may directly modulate GABA synthesis pathways in this brain region. Further studies are needed to elucidate the functional importance of these ARC POMC GABAergic neurocircuits to the depressor effects of Ang-(1-7) in obesity. Funding: NIH R01 HL156986. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Antihypertensive effect of chicken blood peptide hydrolysate in streptozotocin-induced diabetic rats

Chicken blood peptide hydrolysate (CBH) has been reported to exert antioxidant, angiotensin 1-converting enzyme (ACE) inhibitory, and cholesterol-lowering activities. Antihypertensive effect of the CBPH was also demonstrated in spontaneously hypertensive rats. This study aimed to assess the anti-diabetic and antihypertensive effect of the CBH in streptozotocin (STZ)-induced diabetic rats. CBH was prepared from fresh chicken blood collected from an industrial slaughterhouse in Nakhon Ratchasima, Thailand. Adult male Wistar rats were randomly divided into 2 main groups: normal and STZ-induced diabetes mellitus (DM) groups. Five subgroups of each main group were given distilled water, metformin (200 mg/kg), and CBH (300, 600, 1200 mg/kg) by oral gavage for 28 days (n=10 per each group). Fasting blood sugar level and OGTT were evaluated before and at the end of experiment. Each rat underwent monitoring of blood pressure using femoral artery. STZ-induced diabetic rats showed higher fasting blood glucose concentration and area under curve from OGTT than normal rats, which was not reduced by all treatments. STZ-induced diabetic rats showed higher mean arterial blood pressure than normal rats, which was significantly reduced by metformin and CBH (300 and 1200 mg/kg) (p<0.05). The blood pressure-lowering effect of CBH suggested the potential for the application of CBH in the management of diabetic hypertension. However, attention must be paid to concerns about bird flu in certain places and prohibition of the use of blood product. This work was supported by Suranaree University of Technology (SUT), Thailand Science Research and Innovation (TSRI), and National Science Research and Innovation Fund (NSRF) (FF1-111-65-12-30(08)). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Effect of Histamine H2 Receptor Antagonists on All-Cause Mortality in Critically Ill Patients With Essential Hypertension: A Retrospective Cohort Study.

Previous studies found that histamine H2 receptor antagonists (H2RAs) had blood pressure lowering and cardioprotective effects, but the impact of H2RAs on the survival outcomes of critically ill patients with essential hypertension is still unclear. The aim of this study was to investigate the association of H2RAs exposure with all-cause mortality in patients with essential hypertension based on Medical Information Mart for Intensive Care III database. A total of 17,739 patients were included, involving 8482 H2RAs users and 9257 non-H2RAs users. Propensity score matching (PSM) was performed to improve balance between 2 groups that were exposed to H2RAs or not. Kaplan-Meier survival curves were used to compare the cumulative survival rates and multivariable Cox regression models were performed to evaluate the association between H2RAs exposure and all-cause mortality. After 1:1 PSM, 4416 pairs of patients were enrolled. The results revealed potentially significant association between H2RAs exposure and decreased 30-day, 90-day, and 1-year mortalities in multivariate analyses (HR = 0.783, 95% CI: 0.696-0.882 for 30-day; HR = 0.860, 95% CI: 0.778-0.950 for 90-day; and HR = 0.883, 95% CI: 0.811-0.961 for 1-year mortality, respectively). Covariate effect analyses showed that the use of H2RAs was more beneficial in essential hypertension patients with age ≥ 60, BMI ≥ 25 kg/m2, coronary arteriosclerosis, stroke, and acute kidney failure, respectively. In conclusion, H2RAs exposure was related to lower mortalities in critically ill patients with essential hypertension, which provided novel potential strategy for the use of H2RAs in essential hypertension patients.

The effect of intensive blood pressure lowering on left ventricular hypertrophy in patients with hypertension: a systematic review and meta-analysis of randomized controlled trials

Background We conducted a comprehensive systematic review to examine the efficacy of intensive blood pressure lowering on the risk of left ventricular hypertrophy (LVH). Methods We searched PubMed, Scopus, Web of Science, Cochrane Central, and EMBASE for all relevant randomized controlled trials. The primary outcome was the incidence of left ventricular hypertrophy. We used the risk ratio (RR) and hazard ratio (HR) with a 95% confidence interval as our effect sizes. Results Four studies, comprising 20,747 patients, were included. Intensive blood pressure lowering was linked with a diminished LVH incidence (RR: 0.66, 95% CI [0.56–0.77]). We also found that intensive blood pressure lowering increased the risk of LVH regression in patients with baseline LVH (RR: 1.21, 95% CI [1.11–1.32]). Finally, intensive blood pressure lowering was linked with a reduced risk of cardiovascular disease (HR: 0.71, 95% CI [0.60–0.85]). No significant heterogeneity was seen in either outcome. Conclusion Our study suggests that intensive blood pressure lowering effectively reduces the risk of LVH and cardiovascular disease. An interactive version of our analysis can be accessed here: https://databoard.shinyapps.io/lvh_hypertophy/

Study on genotype and phenotype of novel CYP2D6 variants using pharmacokinetic and pharmacodynamic models with metoprolol as a substrate drug.

To investigate the pharmacokinetic and pharmacodynamic profiles of volunteers carrying CYP2D6 genotypes with unknow metabolic phenotypes, a total of 22 volunteers were recruited based on the sequencing results. Peripheral blood and urine samples were collected at specific time points after oral administration of metoprolol. A validated high-performance liquid chromatography (HPLC) method was used to determine the concentrations of metoprolol and α-hydroxymetoprolol. Blood pressure and electrocardiogram were also monitored. The results showed that the main pharmacokinetic parameters of metoprolol in CYP2D6*1/*34 carriers are similar to those in CYP2D6*1/*1 carriers. However, in individuals carrying the CYP2D6*10/*87, CYP2D6*10/*95, and CYP2D6*97/*97 genotypes, the area under the curve (AUC) and half-life (t1/2) of metoprolol increased by 2-3 times compared to wild type. The urinary metabolic ratio of metoprolol in these genotypes is consistent with the trends observed in plasma samples. Therefore, CYP2D6*1/*34 can be considered as normal metabolizers, while CYP2D6*10/*87, CYP2D6*10/*95, and CYP2D6*97/*97 are intermediate metabolizers. Although the blood concentration of metoprolol has been found to correlate with CYP2D6 genotype, its blood pressure-lowering effect reaches maximum effectiveness at a reduction of 25 mmHg. Furthermore, P-Q interval prolongation and heart rate reduction are not positively correlated with metoprolol blood exposure. Based on the pharmacokinetic-pharmacodynamic model, this study clarified the properties of metoprolol in subjects with novel CYP2D6 genotypes and provided important fundamental data for the translational medicine of this substrate drug.

Vasorelaxant and Blood Pressure-Lowering Effects of Cnidium monnieri Fruit Ethanol Extract in Sprague Dawley and Spontaneously Hypertensive Rats.

Cnidium monnieri (L.) Cusson, a member of the Apiaceae family, is rich in coumarins, such as imperatorin and osthole. Cnidium monnieri fruit (CM) has a broad range of therapeutic potential that can be used in anti-bacterial, anti-cancer, and sexual dysfunction treatments. However, its efficacy in lowering blood pressure through vasodilation remains unknown. This study aimed to assess the potential therapeutic effect of CM 50% ethanol extract (CME) on hypertension and the mechanism of its vasorelaxant effect. CME (1-30 µg/mL) showed a concentration-dependent vasorelaxation on constricted aortic rings in Sprague Dawley rats induced by phenylephrine via an endothelium-independent mechanism. The vasorelaxant effect of CME was inhibited by blockers of voltage-dependent and Ca2+-activated K+ channels. Additionally, CME inhibited the vascular contraction induced by angiotensin II and CaCl2. The main active compounds of CM, i.e., imperatorin (3-300 µM) and osthole (1-100 µM), showed a concentration-dependent vasorelaxation effect, with half-maximal effective concentration values of 9.14 ± 0.06 and 5.98 ± 0.06 µM, respectively. Orally administered CME significantly reduced the blood pressure of spontaneously hypertensive rats. Our research shows that CME is a promising treatment option for hypertension. However, further studies are required to fully elucidate its therapeutic potential.

Assessment of Registered Clinical Trial Designs: Comparison of L-Arginine and/or L-Citrulline Interventions for Hypertension.

L-Arginine (Arg) is an essential amino acid and a precursor for the synthesis of vascular nitric oxide, while L-Citrulline is a non-essential amino acid substrate for increasing L-arginine. Both L-arginine and L-Citrulline in translational studies may acutely lower the blood pressure. Current meta-analysis for L-arginine or L-Citrulline interventions in blood pressure have identified significant heterogeneity. Clinical trial evidence for L-arginine or L-Citrulline in chronic blood pressure reduction in the general population requires an examination of trial designs, as not all translational studies may have influenced vascular reactivity. Our aims are to explore whether L-arginine and L-citrulline intervention trials in chronic blood pressure consider standardized end points relevant to the general adult populations. A step-wise search on clinicaltrials.gov, the U.S. Library of Medicine registry for clinical trials, was performed including the following keyword search parameters: "completed" "L-Citrulline" "L-arginine" trial", and "adults", involving "blood pressure" reduction as a primary end point in adult humans. Of the forty-four completed trials, only five were included for analysis. Following the careful evaluation of trial design, we observed heterogeneity across participant inclusion criteria (population sample size, age range, sex), interventional design (dosages, duration), and primary outcomes, measured with respect to changes in diastolic or systolic blood pressure. In conclusion, there is a lack of robust trial design evidence to suggest that L-arginine or L-Citrulline, based on current RCTs in the general population, have an overall positive effect on vascular endothelial reactivity and a beneficial chronic blood pressure-lowering effect. Indeed, conclusions drawn from human meta-analysis studies have been heterogenous between studies, which may be attributed to study design heterogeneity, including differences in sample population, age, and blood pressure at the time of entry. Inconsistencies in the study design poses a challenge for systematic reviews and meta-analysis to accurately assess the effect size and impact of L-arginine or L-citrulline on both systolic and diastolic blood pressure.

A novel angiotensin I-converting enzyme inhibitory peptide from walnut (Juglans sigillata) protein hydrolysates and its evaluation in Ang II-induced HUVECs and hypertensive rats

This study aims to seek angiotensin-I-converting enzyme inhibitory (ACEi) peptides from walnut using different enzymatic hydrolysis, and further to validate the potent ACEi peptides identified and screened via peptidomics and in silico analysis against hypertension in spontaneously hypertensive rats (SHRs). Results showed that walnut protein hydrolysate (WPH) prepared by combination of alcalase and simulated gastrointestinal digestion exhibited high ACEi activity. WPH was separated via Sephadex-G25, and four peptides were identified, screened and verified based on their PeptideRanker score, structural characteristic and ACE inhibition. Interestingly, FDWLR showed the highest ACEi activity with IC50 value of 8.02 μg/mL, which might be related to its close affinity with ACE observed in molecular docking. Subsequently, high absorption and non-toxicity of FDWLR was predicted via in silico absorption, distribution, metabolism, excretion and toxicity. Furthermore, FDWLR exhibited positively vasoregulation in Ang II-induced human umbilical vein endothelial cells, and great blood pressure lowering effect in SHRs.

Targeting Hypertension: A Review on Pathophysiological Factors and Treatment Strategies.

Hypertension is one of the primary causes of cardiovascular diseases and death, with a higher prevalence in low- and middle-income countries. The pathophysiology of hypertension remains complex, with 2% to 5% of patients having underlying renal or adrenal disorders. The rest are referred to as essential hypertension, with derangements in various physiological mechanisms potentially contributing to the development of essential hypertension. Hypertension elevates the risk of cardiovascular disease (CVD) events (coronary heart disease, heart failure, and stroke) and mortality. First-line therapy for hypertension is lifestyle change, which includes weight loss, a balanced diet that includes low salt and high potassium intake, physical exercise, and limitation or elimination of alcohol use. Blood pressure-lowering effects of individual lifestyle components are partially additive, enhancing the efficacy of pharmaceutical treatment. The choice to begin antihypertensive medication should be based on the level of blood pressure and the existence of a high atherosclerotic CVD risk. First-line hypertension treatment includes a thiazide or thiazide-like diuretic, an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, and a calcium channel blocker. Addressing hypertension will require continued efforts to improve access to diagnosis, treatment, and lifestyle interventions.

Effect of Saccharina japonica Intake on Blood Pressure and Gut Microbiota Composition in Spontaneously Hypertensive Rats.

It was reported that the consumption of Saccharina japonica (SJ) lowers blood pressure (BP) in hypertensive rats. Hypertension is related to gut microbiota, and hypertensive patients develop dysbiosis. It was reported that the intake of dietary fiber and polysaccharides contained in SJ changes gut microbiota and increases short-chain fatty acids (SCFAs). The present study examined the effect of BP lowering by SJ in spontaneously hypertensive rats (SHRs) and observed changes in gut microbiota composition and SCFAs concentration. Male SHRs and Wistar Kyoto rats (WKYs) were fed a diet containing 5% SJ or a control diet for six weeks. We measured systolic BP (SBP) weekly, as well as mean arterial BP (MAP), the 16S rRNA gene, and SCFAs in the cecal contents at the end of the period. As a result, the intake of SJ significantly decreased SBP and MAP in SHRs. As well, it significantly changed the microbial diversity by altering the gut microbiota composition. Particularly, it increased the abundance of Bacteroides acidifaciens, which may be associated with the antihypertensive effect of SJ. Thus, SJ intake suppressed the increase in BP and altered the gut microbiota composition, although it did not significantly change the SCFAs concentration in the cecal contents.

The short-term effect of Blood Pressure Reduction after Biofeedback in Malignant Hypertension: A case report

Objectives: The purpose of this study was to report the short-term blood pressure-lowering effects observed in a patient with malignant hypertension through slow breathing maneuver with heart rate variability(HRV) biofeedback.Methods: Biofeedback sessions, totaling 13, each lasting 10 minutes, were administered. Blood pressure was measured pre and post-treatment, as well as thrice daily at 10 am, 4 pm, and 8 pm. Systolic blood pressure(SBP), diastolic blood pressure(DBP), and pulse rate were recorded for comparative analysis.Results: Before biofeedback, the average SBP, DBP, and pulse rate were 227.2±18.3, 135.2±11.0, and 104.4±5.3, respectively. Immediately post-biofeedback, these values changed to 213.7±15.2, 126.9±8.5, and 99.2±3.6. However, sustained long-term blood pressure reduction was not observed.Conclusions: The findings suggest that biofeedback therapy induces a short-term reduction in blood pressure in cases of malignant hypertension, potentially associated with autonomic nervous system regulation. Integrating biofeedback with other Korean medicine treatments, such as acupuncture or moxibustion, may offer a comprehensive approach for managing malignant hypertension.

Affinin, Isolated from Heliopsis longipes, Induces an Antihypertensive Effect That Involves CB1 Cannabinoid Receptors and TRPA1 and TRPV1 Channel Activation.

In previous studies, we demonstrated that the ethanolic extract of Heliopsis longipes roots and its main alkamide, affinin, elicit a vasorelaxant effect through a mechanism involving activation of the gasotransmitter pathways and stimulation of cannabinoid type 1 receptors and transient receptor potential ankyrin 1 and transient receptor potential vanilloid 1 channels. However, it has not yet been demonstrated whether the EEH and affinin are capable of lowering high blood pressure. Therefore, the aim of the present study was to determine the effect of the oral administration of the EEH and affinin on the systolic blood pressure of NG-nitro-L-arginine methyl ester-induced hypertensive rats and to explore the participation of cannabinoid receptors and transient receptor potential channels in the mechanism of action of this alkamide. Our results showed that the ethanolic extract of H. longipes and affinin significantly lowered systolic blood pressure and induced an improvement in endothelial function, which is associated with increased serum nitric oxide levels. Inhibition of cannabinoid type 1 receptors by rimonabant (3 mg/kg), transient receptor potential ankyrin 1 channels by HC-030031 (8 mg/kg), and transient receptor potential vanilloid 1 channels by capsazepine (5 mg/kg) significantly decreased the antihypertensive effect induced by affinin, suggesting that the blood pressure-lowering effect of this alkamide involves activation of cannabinoid type 1 receptors and transient receptor potential ankyrin 1 and transient receptor potential vanilloid 1 channels.

Predictors of blood pressure response to continuous positive airway pressure treatment in patients with sleep apnea.

Sleep apnea is associated with hypertension. Metaanalyses indicate that treatment of sleep apnea by continuous positive airway pressure (CPAP) reduces blood pressure (BP) by a mean of 3 mmHg. To date, predictors of BP response to CPAP remain incompletely understood. We hypothesized that the magnitude of CPAP-induced BP reduction depends on baseline apnea-hypopnea index (AHI) and the extent of daytime sleepiness. We performed a retrospective study on the association of BP response to CPAP with polysomnographic readings, intensity of sleepiness (measured by Epworth Sleepiness Scale, ESS), and epidemiologic parameters in 2461 patients with obstructive sleep apnea. BP response was defined as the difference between office BP at polysomonography examinations before and after initiation of CPAP. Five hundred and fifty-five patients fulfilled all inclusion and exclusion criteria and were included in the analysis. Median monthly CPAP usage was 143.7 h (85.4-204.1 h). BP was significantly higher at baseline than at follow-up (129.9 ± 15.5 vs. 128.3 ± 15.2, P = 0.021) resulting in mean reduction of BP of -1.5 ± 19.2 mmHg. patients with a higher than median baseline AHI (median 21) showed a more pronounced reduction of BP than those with lower AHI (AHI ≥21: 130.5 ± 15.3 vs. 128.6 ± 14.6, P = 0.06; AHI <21: 129.5 ± 15.8 vs. 127.9 ± 15.8, P = 0.18). CPAP therapy led to a significant reduction in sleepiness (8.3 ± 4.8 vs. 6.6 ± 4.5, P < 0.0001). Those subjects with higher than median sleepiness score (ESS ≥8), however, did not show a significant difference in BP response compared with those with a lower sleepiness score. Receiver-operating characteristic (ROC) curve analyses investigating the accuracy of AHI and ESS to predict a BP reduction at least 5 mmHg revealed an AUC of 0.51 and 0.52, respectively. The study confirms that CPAP therapy for sleep apnea has a mild BP lowering effect. Although this effect is slightly higher in patients with above-average AHI, neither AHI nor ESS can be used to define threshold values predicting a BP decrease at least 5 mmHg.

Vasodilation and Blood Pressure-Lowering Effect of 3-Demethyl-2-Geranyl-4-Prenylbellidifoline, a Xanthone Obtained from Garcinia achachairu, in Hypertensive Rats.

3-demethyl-2-geranyl-4-prenylbellidifoline (DGP), a natural xanthone isolated from Garcinia achachairu, has previously demonstrated remarkable diuretic and renal protective actions. The present study expands its actions on the cardiovascular system by evaluating its vasorelaxant and blood pressure-lowering effects in spontaneously hypertensive rats (SHRs). Aortic endothelium-intact (E+) preparations of SHRs pre-contracted by phenylephrine and exposed to cumulative concentrations of G. achachairu extract, fractions, and DGP exhibited a significant relaxation compared to vehicle-only exposed rings. The non-selective muscarinic receptor antagonist (atropine), the non-selective inhibitor of nitric oxide synthase (L-NAME), as well as the inhibitor of soluble guanylate cyclase (ODQ) altogether avoided DGP-induced relaxation. Tetraethylammonium (small conductance Ca2+-activated K+ channel blocker), 4-aminopyridine (a voltage-dependent K+ channel blocker), and barium chloride (an influx-rectifying K+ channel blocker) significantly reduced DGP capacity to induce relaxation without the interference of glibenclamide (an ATP-sensitive inward rectifier 6.1 and 6.2 K+ channel blocker). Additionally, administration of DGP, 1 mg/kg i.v., decreased the mean, systolic, and diastolic arterial pressures, and the heart rate of SHRs. The natural xanthone DGP showed promising potential as an endothelium-dependent vasorelaxant, operating through the nitric oxide pathway and potassium channels, ultimately significantly reducing blood pressure in hypertensive rats.

Plant-based diets in patients with chronic kidney disease.

Dietary protein restriction has been considered to be a nutritional-related strategy to reduce risk for end-stage kidney disease among patients with non-dialysis-dependent chronic kidney disease (CKD). However, there is insufficient evidence to recommend a particular type of protein to slow down the CKD progression. Recently, various plant-based diets could demonstrate some additional benefits such as a blood pressure-lowering effect, a reduction of metabolic acidosis as well as hyperphosphatemia, and gut-derived uremic toxins. Furthermore, the former concerns about the risk of undernutrition and hyperkalemia observed with plant-based diets may be inconsistent in real clinical practice. In this review, we summarize the current evidence of the proposed pleiotropic effects of plant-based diets and their associations with clinical outcomes among pre-dialysis CKD patients.

Sakuranetin as a Potential Regulator of Blood Pressure in Spontaneously Hypertensive Rats by Promoting Vasorelaxation through Calcium Channel Blockade.

Natural compounds, known for diverse pharmacological properties, have attracted attention as potential sources for hypertension treatment. Previous studies have revealed the hypotensive effect and vascular relaxation of prunetin, a natural compound derived from Prunus yedoensis. However, the potential blood pressure-lowering and vasorelaxant effects of sakuranetin, another representative compound found in plants belonging to the genus Prunus, have remained unexplored. We aimed to fill this gap by investigating the hypotensive and vasorelaxant effects of sakuranetin in rats. Results indicated that sakuranetin, particularly in the sakuranetin 20 mg/kg group, led to significant reductions in systolic blood pressure (SBP) and diastolic blood pressure (DBP) by -14.53 ± 5.64% and -19.83 ± 6.56% at 4 h after administration. In the sakuranetin 50 mg/kg group, the SBP and DBP decreased by -13.27 ± 6.86% and -16.62 ± 10.01% at 2 h and by -21.61 ± 4.49% and -30.45 ± 5.21% at 4 h after administration. In addition, we identified the vasorelaxant effects of sakuranetin, attributing its mechanisms to the inhibition of calcium influx and the modulation of angiotensin II. Considering its hypotensive and vasorelaxant effects, sakuranetin could potentially serve as an antihypertensive agent. However, further research is required to evaluate the safety and long-term efficacy.

Blood pressure lowering enhances cerebrospinal fluid efflux to the systemic circulation primarily via the lymphatic vasculature

BackgroundInside the incompressible cranium, the volume of cerebrospinal fluid is directly linked to blood volume: a change in either will induce a compensatory change in the other. Vasodilatory lowering of blood pressure has been shown to result in an increase of intracranial pressure, which, in normal circumstances should return to equilibrium by increased fluid efflux. In this study, we investigated the effect of blood pressure lowering on fluorescent cerebrospinal fluid tracer absorption into the systemic blood circulation.MethodsBlood pressure lowering was performed by an i.v. administration of nitric oxide donor (sodium nitroprusside, 5 µg kg−1 min−1) or the Ca2+-channel blocker (nicardipine hydrochloride, 0.5 µg kg−1 min−1) for 10, and 15 to 40 min, respectively. The effect of blood pressure lowering on cerebrospinal fluid clearance was investigated by measuring the efflux of fluorescent tracers (40 kDa FITC-dextran, 45 kDa Texas Red-conjugated ovalbumin) into blood and deep cervical lymph nodes. The effect of nicardipine on cerebral hemodynamics was investigated by near-infrared spectroscopy. The distribution of cerebrospinal fluid tracers (40 kDa horse radish peroxidase,160 kDa nanogold-conjugated IgG) in exit pathways was also analyzed at an ultrastructural level using electron microscopy.ResultsNicardipine and sodium nitroprusside reduced blood pressure by 32.0 ± 19.6% and 24.0 ± 13.3%, while temporarily elevating intracranial pressure by 14.0 ± 7.0% and 18.2 ± 15.0%, respectively. Blood pressure lowering significantly increased tracer accumulation into dorsal dura, deep cervical lymph nodes and systemic circulation, but reduced perivascular inflow along penetrating arteries in the brain. The enhanced tracer efflux by blood pressure lowering into the systemic circulation was markedly reduced (− 66.7%) by ligation of lymphatic vessels draining into deep cervical lymph nodes.ConclusionsThis is the first study showing that cerebrospinal fluid clearance can be improved with acute hypotensive treatment and that the effect of the treatment is reduced by ligation of a lymphatic drainage pathway. Enhanced cerebrospinal fluid clearance by blood pressure lowering may have therapeutic potential in diseases with dysregulated cerebrospinal fluid flow.