Pathophysiology Of Hypertension Research Articles

Multiple urinary peptides are associated with hypertension: a link to molecular pathophysiology.

Hypertension is a common condition worldwide; however, its underlying mechanisms remain largely unknown. This study aimed to identify urinary peptides associated with hypertension to further explore the relevant molecular pathophysiology. Peptidome data from 2876 individuals without end-organ damage were retrieved from the Human Urinary Proteome Database, belonging to general population (discovery) or type 2 diabetic (validation) cohorts. Participants were divided based on systolic blood pressure (SBP) and diastolic BP (DBP) into hypertensive (SBP ≥140 mmHg and/or DBP ≥90 mmHg) and normotensive (SBP <120 mmHg and DBP <80 mmHg, without antihypertensive treatment) groups. Differences in peptide abundance between the two groups were confirmed using an external cohort ( n = 420) of participants without end-organ damage, matched for age, BMI, eGFR, sex, and the presence of diabetes. Furthermore, the association of the peptides with BP as a continuous variable was investigated. The findings were compared with peptide biomarkers of chronic diseases and bioinformatic analyses were conducted to highlight the underlying molecular mechanisms. Between hypertensive and normotensive individuals, 96 (mostly COL1A1 and COL3A1) peptides were found to be significantly different in both the discovery (adjusted) and validation (nominal significance) cohorts, with consistent regulation. Of these, 83 were consistently regulated in the matched cohort. A weak, yet significant, association between their abundance and standardized BP was also observed. Hypertension is associated with an altered urinary peptide profile with evident differential regulation of collagen-derived peptides. Peptides related to vascular calcification and sodium regulation were also affected. Whether these modifications reflect the pathophysiology of hypertension and/or early subclinical organ damage requires further investigation.

Markers of Vascular Dysfunction in Hypertension.

Hypertension is a modifiable cardiovascular risk factor and displays a rapidly growing incidence due to aging and the acquisition of an unhealthy lifestyle. Hypertension is linked to the development of target organ damage in several vascular beds such as coronary arteries, peripheral, cerebral, and renal arteries. Besides, along with the presence of other cardiovascular risk factors, it aggravates vascular dysfunction due to the aging process. The mechanisms of vascular dysfunction in hypertension are complex and involve excessive salt intake and water retention, activation of neurohormonal systems, induction of endothelial dysfunction of large arteries and microcirculation, development of arterial stiffness, and complex interactions with cellular pathways of inflammation, oxidative stress, and thrombosis. The extent of vascular dysfunction in patients with hypertension can be assessed by evaluating endothelial function, measuring arterial stiffness, and testing the levels of circulating biomarkers of oxidative stress, pro-inflammatory cytokines, and thrombosis. Assessing these markers in subjects with and without hypertension could aid in identifying those at risk of vascular damage and improving risk prediction for future cardiovascular events. While several lifestyle and pharmacological therapies have shown promise in addressing vascular dysfunction in hypertension, none of these biomarkers have been established as an independent risk factor or treatment target. Therefore, in this article, we review the literature on the evidence that exists regarding the role of vascular dysfunction in the pathophysiology, diagnosis, progression, and treatment of hypertension, highlighting the lack of conclusive evidence in this field.

Unraveling the Impact of miR-146a in Pulmonary Arterial Hypertension Pathophysiology and Right Ventricular Function

Pulmonary arterial hypertension (PAH) is a chronic disorder characterized by excessive pulmonary vascular remodeling, leading to elevated pulmonary vascular resistance and right ventricle (RV) overload and failure. MicroRNA-146a (miR-146a) promotes vascular smooth muscle cell proliferation and vascular neointimal hyperplasia, both hallmarks of PAH. This study aimed to investigate the effects of miR-146a through pharmacological or genetic inhibition on experimental PAH and RV pressure overload animal models. Additionally, we examined the overexpression of miR-146a on human pulmonary artery smooth muscle cells (hPASMCs). Here, we showed that miR-146a genic expression was increased in the lungs of patients with PAH and the plasma of monocrotaline (MCT) rats. Interestingly, genetic ablation of miR-146a improved RV hypertrophy and systolic pressures in Sugen 5415/hypoxia (SuHx) and pulmonary arterial banding (PAB) mice. Pharmacological inhibition of miR-146a improved RV remodeling in PAB-wild type mice and MCT rats, and enhanced exercise capacity in MCT rats. However, overexpression of miR-146a did not affect proliferation, migration, and apoptosis in control-hPASMCs. Our findings show that miR-146a may play a significant role in RV function and remodeling, representing a promising therapeutic target for RV hypertrophy and, consequently, PAH.

Rare Adverse Effect of a Commonly Used Drug in Chronic Kidney Disease

Chronic kidney disease (CKD) and hypertension can lead to each other. Majority of the patients with CKD have hypertension.Sympathetic overactivity has been suggested as one of the important etiologies of hypertension in CKD patients. Clonidine isused as a central sympatholytic to control hypertension in CKD patients. Drug-induced sialadenitis has been reported withmultiple drugs including antihypertensives. We report a case of clonidine-induced sialadenitis, which has been rarely seendespite the widespread use of this drug among CKD patients requiring multiple antihypertensive drugs.

The Construction and Meaning of Race Within Hypertension Guidelines: A Systematic Scoping Review.

Professional society guidelines are evidence-based recommendations intended to promote standardized care and improve health outcomes. Amid increased recognition of the role racism plays in shaping inequitable healthcare delivery, many researchers and practitioners have critiqued existing guidelines, particularly those that include race-based recommendations. Critiques highlight how racism influences the evidence that guidelines are based on and its interpretation. However, few have used a systematic methodology to examine race-based recommendations. This review examines hypertension guidelines, a condition affecting nearly half of all adults in the United States (US), to understand how guidelines reference and develop recommendations related to race. A systematic scoping review of all professional guidelines on the management of essential hypertension published between 1977 and 2022 to examine the use and meaning of race categories. Of the 37 guidelines that met the inclusion criteria, we identified a total of 990 mentions of race categories.Black and African/African American were the predominant race categories referred to in guidelines (n = 409). Guideline authors used race in five key domains: describing the prevalence or etiology of hypertension; characterizing prior hypertension studies; describing hypertension interventions; social risk and social determinants of health; the complexity of race. Guideline authors largely used race categories as biological rather than social constructions. None of the guidelines discussed racism and the role it plays in perpetuating hypertension inequities. Hypertension guidelines largely refer to race as a distinct and natural category rather than confront the longstanding history of racism within and beyond the medical system.Normalizing race as a biological rather than social construct fails to address racism as a key determinant driving inequities in cardiovascular health. These changes are necessary to produce meaningful structural solutions that advance equity in hypertension education, research, and care delivery.

The RICA-2 registry: design and baseline characteristics of the first 1,000 patients

Background and objectiveHeart failure (HF) is a syndrome of epidemic proportions and one of the main reasons for hospital admission. Patient registries provide real-world clinical practice information which is complementary to clinical trials. RICA-2 is a registry of the Spanish Society of Internal Medicine. Its main goal is to know the clinical and epidemiological characteristics and prognostic factors of patients with HF treated in Internal Medicine Departments. The objective of this study is to present the design of the RICA-2, the baseline characteristics of the first 1000 patients included and their comparison with those of the historical cohort of the RICA registry. MethodsObservational, multicentre and prospective study of patients with HF with the following inclusion criteria: age equal to or greater than 18 years old, diagnosis of HF according to the European Guidelines, indistinct inclusion in decompensation or stable phase, of patients with de novo HF or chronic HF, regardless of left ventricular ejection fraction, aetiology and comorbidities. ResultsRICA-2 patients have advanced age (83 years old) and 51% are women. The comorbidity burden is higher than in the RICA registry (5 points in the Charlson comorbidity index), with predominating chronic decompensated HF (74%), hypertensive aetiology (39%) and preserved ejection fraction (52%). Most patients are pre-frail or vulnerable and are at risk of malnutrition. ConclusionThe RICA-2 represents a contemporary cohort of patients that will provide us with clinical, epidemiological and prognostic information on patients with acute and chronic HF treated in Internal Medicine.

Pathophysiology and therapeutic options for cirrhotic portal hypertension.

Portal hypertension represents the primary non-neoplastic complication of liver cirrhosis and has life-threatening consequences, such as oesophageal variceal bleeding, ascites, and hepatic encephalopathy. Portal hypertension occurs due to increased resistance of the cirrhotic liver vasculature to portal blood flow and is further aggravated by the hyperdynamic circulatory syndrome. Existing knowledge indicates that the profibrogenic phenotype acquired by sinusoidal cells is the initial factor leading to increased hepatic vascular tone and fibrosis, which cause increased vascular resistance and portal hypertension. Data also suggest that the phenotype of hepatic cells could be further impaired due to the altered mechanical properties of the cirrhotic liver itself, creating a deleterious cycle that worsens portal hypertension in the advanced stages of liver disease. In this Review, we discuss recent discoveries in the pathophysiology and treatment of cirrhotic portal hypertension, a condition with few pharmacological treatment options.

Causal association between blood metabolites and risk of hypertension: a Mendelian randomization study.

Previous studies have indicated a strong link between blood metabolites and hypertension, however the causality of metabolites and hypertension is unknown. Two-sample Mendelian randomization (MR) analysis was performed to assess the causal relationship between 486 blood metabolites and essential hypertension (EHT). Blood metabolite GWAS data was utilized as the exposure, with EHT GWAS data as the outcome. To further verify the results, another different source of EHT GWAS data was repeatedly analyzed. The major MR analytic approach used to determine causality was inverse variance weighted (IVW), with MR-Egger, Weighted Median, and MR-PRESSO models serving as supplements. We used the Cochran Q test to examine heterogeneity. Horizontal pleiotropy was examined using MR-Egger intercept and MR-PRESSO global test. The MR Steiger test confirmed the causal relationship between blood metabolites and EHT. In this study, nine blood metabolites associated with EHT were preliminarily identified by MR analysis, including four known metabolites (N-acetylornithine, X-12510-2-aminooctanoic acid, creatine, hexadecanedioate) and five unknown metabolites. Then another source of EHT GWAS data was repeatedly analyzed for further verification, and two overlapped metabolites (N-acetylornithine, X-12510-2-aminooctanoic acid) were found. There was a negative correlation between N-acetylornithine and EHT (OR = 0.987, 95% CI = 0.980-0.993, P = 1.01 × 10-4), Cochran's Q test suggested there was no heterogeneity (Q = 31.7586, P = 0.1331), MR-Egger intercept and MR-PRESSO global test suggested there was no horizontal pleiotropy (P > 0.05), Leave-one-out analysis indicated that no single single-nucleotide polymorphism (SNP) had a significant effect on the results, and MR Steiger test confirmed that the direction of causality was correct (P < 0.001). There was a negative correlation between X-12510-2-aminooctanoic acid and EHT (OR = 0.982, 95% CI = 0.972-0.993, P = 0.0017), and there was no evidence of heterogeneity or pleiotropy in multiple sensitivity analyses. The study discovered some blood metabolites causally linked to EHT, which might lead to new understandings of the pathophysiology of hypertension.

Prevalence and Characteristics of Low-renin Hypertension in a Primary Care Population.

Low-renin hypertension is an underrecognized subtype of hypertension with specific treatment options. This study aims to identify the prevalence in primary care and to compare patient characteristics to those with normal-renin hypertension and primary aldosteronism (PA). In a cohort study, patients with treatment-naïve hypertension were screened for PA with plasma aldosterone and direct renin concentrations. Patients with an elevated aldosterone-to-renin ratio [≥70 pmol/mU (≥2.5 ng/dL:mU/L)] underwent confirmatory testing. All screened patients were then classified as having (1) normal-renin hypertension, (2) low-renin hypertension (direct renin concentration <10mU/L (plasma renin activity ∼<1 ng/mL/hour) and not meeting the criteria for PA), or (3) confirmed PA. Of the 261 patients, 69 (26.4%) had low-renin hypertension, 136 (51.9%) had normal renin hypertension, and 47 (18.0%) had PA. Patients with low-renin hypertension were older and more likely to be female compared to normal-renin hypertension (57.1 ± 12.8 years vs 51.8 ± 14.0 years, P < .05 and 68.1% vs 49.3%, P < .05, respectively) but similar to PA (53.5 ± 11.5 years and 55.3%). However, in an adjusted binomial logistic regression, there was no association between increasing age or sex and low-renin hypertension. The median aldosterone concentration was lower compared to patients with normal-renin hypertension and PA: 279 pmol/L (216-355) vs 320 pmol/L (231-472), P < .05 and 419 pmol/L (360-530), P < .001. At least a quarter of treatment-naïve hypertensive patients in primary care had a low direct renin concentration but did not meet the criteria for PA. Patient characteristics were similar, aside from a lower aldosterone concentration compared to patients with normal-renin hypertension and PA. Further research is needed to understand the underlying pathophysiology of low-renin hypertension and the optimal first-line treatment.

Controversies in the pathophysiology of arterial hypertension.

Introduction: Purinergic receptors actively participate in the renal alterations in high blood pressure. The elevation of ATP in the renal interstitium activates purinergic receptors, constituting a fundamental pathway in the generation and persistence of arterial hypertension. Objective of the review: This article is a narrative review that aims to show the importance of new concepts in the pathophysiology of arterial hypertension. Essential points of the review: Purinergic receptors are ATP receptors; the more significant the ATP, the greater the purinergic receptors. Elevated ATP concentrations alter fundamental mechanisms related to blood pressure control, such as the pressure natriuresis mechanism and renal sodium excretion, the regulation of glomerular filtration, and the tubuloglomerular feedback mechanism. The alteration of these mechanisms decreases urinary sodium excretion. Whether influenced by genetic alterations or induced by vasoconstrictor peptides, a decrease in renal function and tubulointerstitial injury occur before the glomerulus is injured. The interaction between angiotensin II and purinergic receptors favors the progression of kidney damage. Conclusion: Kidney damage in high blood pressure is critical, so efforts should be made to control hypertension to prevent the progression of kidney damage that leads to kidney failure. To obtain better blood pressure control, developing purinergic receptor antagonists for clinical use is possible.

Natriuretic peptide system in hypertension: Current understandings of its regulation, targeted therapies and future challenges

The natriuretic peptide system (NPS) is the key driving force of the heart's endocrine function. Recent developments in NPS-targeted therapies have been found promising and effective against cardiovascular diseases, including hypertension. Notably, after discovering crosstalk between NPS and the renin-angiotensin-aldosterone system (RAAS), various combinations such as neprilysin/angiotensin II receptor type 1 AT1 receptor inhibitors and neprilysin/renin inhibitors have been preclinically and clinically tested against various cardiac complications. However, the therapeutic effects of such combinations on the pathophysiology of hypertension are poorly understood. Furthermore, the complicated phenomena underlying NPS regulation and function, particularly in hypertension, are still unexplored. Mounting evidence suggests that numerous regulatory mechanisms modulate the expression of NPS, which can be used as potential targets against hypertension and other cardiovascular diseases. Therefore, this review will specifically focus on epigenetic and other regulators of NPS, identifying prospective regulators that might serve as new therapeutic targets for hypertension. More importantly, it will shed light on recent developments in NPS-targeted therapies, such as M-atrial peptides, and their latest combinations with RAAS modulators, such as S086 and sacubitril-aliskiren. These insights will aid in the development of effective therapies to break the vicious cycle of high blood pressure during hypertension, ultimately addressing the expanding global heart failure pandemic.

A Lifelike guided journey through the pathophysiology of pulmonary hypertension—from measured metabolites to the mechanism of action of drugs

IntroductionPulmonary hypertension (PH) is a pathological condition that affects approximately 1% of the population. The prognosis for many patients is poor, even after treatment. Our knowledge about the pathophysiological mechanisms that cause or are involved in the progression of PH is incomplete. Additionally, the mechanism of action of many drugs used to treat pulmonary hypertension, including sotatercept, requires elucidation.MethodsUsing our graph-powered knowledge mining software Lifelike in combination with a very small patient metabolite data set, we demonstrate how we derive detailed mechanistic hypotheses on the mechanisms of PH pathophysiology and clinical drugs.ResultsIn PH patients, the concentration of hypoxanthine, 12(S)-HETE, glutamic acid, and sphingosine 1 phosphate is significantly higher, while the concentration of L-arginine and L-histidine is lower than in healthy controls. Using the graph-based data analysis, gene ontology, and semantic association capabilities of Lifelike, led us to connect the differentially expressed metabolites with G-protein signaling and SRC. Then, we associated SRC with IL6 signaling. Subsequently, we found associations that connect SRC, and IL6 to activin and BMP signaling. Lastly, we analyzed the mechanisms of action of several existing and novel pharmacological treatments for PH. Lifelike elucidated the interplay between G-protein, IL6, activin, and BMP signaling. Those pathways regulate hallmark pathophysiological processes of PH, including vasoconstriction, endothelial barrier function, cell proliferation, and apoptosis.DiscussionThe results highlight the importance of SRC, ERK1, AKT, and MLC activity in PH. The molecular pathways affected by existing and novel treatments for PH also converge on these molecules. Importantly, sotatercept affects SRC, ERK1, AKT, and MLC simultaneously. The present study shows the power of mining knowledge graphs using Lifelike’s diverse set of data analytics functionalities for developing knowledge-driven hypotheses on PH pathophysiological and drug mechanisms and their interactions. We believe that Lifelike and our presented approach will be valuable for future mechanistic studies of PH, other diseases, and drugs.

Immunological insights into hypertension: unraveling triggers and potential therapeutic avenues.

Hypertension remains the leading cause of morbidity and mortality worldwide. Despite its prevalence, the development of novel antihypertensive therapies has only recently accelerated, with novel agents not yet commercialized, leaving a substantial proportion of individuals resistant to existing treatments. The intricate pathophysiology of hypertension is now understood to involve chronic low-grade inflammation, which places the immune system in the spotlight as a potential target for new therapeutics. This review explores the factors that initiate and sustain an immune response in hypertension, offering insights into potential targets for new treatments. Several factors contribute to immune activation in hypertension, including diet and damage-associated molecular pattern (DAMP) generation. Diets rich in fat or sodium can promote inflammation by inducing intestinal barrier dysfunction and triggering salt-sensitive receptors in T cells and dendritic cells. DAMPs, such as extracellular adenosine triphosphate and heat-shock protein 70, are released during episodes of increased blood pressure, contributing to immune cell activation and inflammation. Unconventional innate-like γδ T cells contribute to initiating and maintaining an immune response through their potential involvement in antigen presentation and regulating cytokine-mediated responses. Immunologic memory, sustained through the formation of effector memory T cells after exposure to hypertensive insults, likely contributes to maintaining an immune response in hypertension. When exposed to hypertensive insults, these memory cells are rapidly activated and contribute to elevated blood pressure and end-organ damage. Evidence from human hypertension, although limited, supports the relevance of distinct immune pathways in hypertension, and highlights the potential of targeted immune interventions in human hypertension. Diet and acute bouts of high blood pressure result in the release of dietary triggers, neoantigens, and damage-associated molecular patterns (DAMPs), which promote immune system activation. Elements such as lipopolysaccharides (LPS), sodium, heat-shock protein (HSP)70, extracellular adenosine triphosphate (eATP), and growth arrest-specific 6 (GAS6) promote activation of innate immune cells such as dendritic cells (DCs) and monocytes (Mo) through their respective receptors (toll-like receptor [TLR]4, amiloride-sensitive epithelial sodium channel [ENaC], TLR2/4, P2X7 receptor [P2RX7], and Axl) leading to costimulatory molecule expression and interleukin (IL)-1β and IL-23 production. The neoantigens HSP70 and isolevuglandins (IsoLGs) are presented to T cells by DCs and possibly γδ T cells, triggering T cell activation, IL-17 and interferon (IFN)-γ production, and the formation of T effector memory (TEM) cells in the kidney, perivascular adipose tissue, bone marrow, and spleen. Exposure of TEM cells to their cognate antigen or previous activating stimuli causes these cells rapid expansion and activation. Cumulatively, this inflammatory state contributes to hypertension and end-organ damage. The figure was created using images from smart.servier.com and is licensed under a Creative Commons Attribution 4.0 license (CC BY 4.0).

Etiologies of Splenic Venous Hypertension: A Review.

Splenic venous hypertension or left-sided portal hypertension is a rare condition caused by an obstruction of the splenic vein. Usually, it presents with upper gastrointestinal bleeding in the absence of liver disease. Etiologies can be classified based on the mechanism of development of splenic vein hypertension: compression, stenosis, inflammation, thrombosis, and surgically decreased splenic venous flow. Diagnosis is established by various imaging modalities and should be suspected in patients with gastric varices in the absence of esophageal varices, splenomegaly, or cirrhosis. The management and prognosis vary depending on the underlying etiology but generally involve reducing splenic venous pressure. The aim of this review was to summarize the etiologies of splenic venous hypertension according to the mechanism of development.

Revisiting resistant hypertension in kidney disease.

As compared to controlled or uncontrolled hypertension, resistant hypertension in patients with chronic kidney disease (CKD) poses a significantly increased healthcare burden due to greater target end-organ damage including cardiovascular disease and CKD progression. Patients with CKD have two to three times higher risk of developing resistant hypertension. True resistant hypertension needs to be distinguished from apparent treatment resistant hypertension (aTRH); however, it is usually not possible in epidemiological studies. Moreover, impact of contemporary guidelines changes in the target blood pressure (BP) goal to less than 130/80 mmHg remains to be determined. Up to half of patients with CKD meet aTRH criteria using 2017 ACC/AHA target BP less than 130/80 mmHg. Excess sodium retention in extracellular and tissue compartment remains the cornerstone cause of resistance to the treatment in CKD. Maximizing and optimizing the diuretic regimen in addition to dietary sodium restriction plays a critical role in these patients. Management requires a trustworthy provider-patient relationship facilitating identification and intervention for the barriers restricting the uptake of lifestyle modifications and medications. Recently, renal denervation has been approved and many other novel agents are on the horizon for treatment of true resistant hypertension associated with CKD. This review discusses the latest in the pathophysiology, definition, identification and treatment strategies of resistant hypertension in individuals with CKD. Further investigations are required to identify the prevalence, future implication and treatment outcome data for true resistant hypertension associated with CKD.

Noninvasive Pressure-Volume Loops Predict Major Adverse Cardiac Events in Heart Failure With Reduced Ejection Fraction

BackgroundHeart failure with reduced ejection fraction (HFrEF) is characterized by ventricular remodeling and impaired myocardial energetics. Left ventricular pressure-volume (PV) loop analysis can be performed noninvasively using cardiovascular magnetic resonance (CMR) imaging to assess cardiac thermodynamic efficiency. ObjectivesThe aim of the study was to investigate whether noninvasive PV loop parameters, derived from CMR, could predict major adverse cardiac events (MACE) in HFrEF patients. MethodsPV loop parameters (stroke work, ventricular efficiency, external power, contractility, and energy per ejected volume) were computed from CMR cine images and brachial blood pressure. The primary endpoint was MACE (cardiovascular death, heart failure (HF) hospitalization, myocardial infarction, revascularization, ventricular tachycardia/fibrillation, heart transplantation, or left ventricular assist device implantation within 5 years). Associations between PV loop parameters and MACE were evaluated using multivariable Cox regression. ResultsA total of 164 HFrEF patients (left ventricular ejection fraction ≤40%, age 63 [IQR: 55-70] years, 79% male) who underwent clinical CMR examination between 2004 and 2014 were included. Eighty-eight patients (54%) experienced at least 1 MACE after an average of 2.8 years. Unadjusted models demonstrated a significant association between MACE and all PV loop parameters (P < 0.05 for all), HF etiology (P < 0.001), left ventricular ejection fraction (P = 0.003), global longitudinal strain (P < 0.001), and N-terminal prohormone of brain natriuretic peptide level (P = 0.001). In the multivariable Cox regression analysis adjusted for age, sex, hypertension, diabetes, and HF etiology, ventricular efficiency was associated with MACE (HR: 1.04, 95% CI: 1.01-1.08, per-% decrease, P = 0.01). ConclusionsVentricular efficiency, derived from noninvasive PV loop analysis from standard CMR scans, is associated with MACE in patients with HFrEF.

Case Report of a Large Endometrioma Precipitating a Hypertensive Emergency [ID 2683395

INTRODUCTION: This is a rare case of a 25-cm endometrioma in a woman who presented in a hypertensive emergency. The hypertension was believed to be secondary to the mass effect of the endometrioma on renal vasculature. METHODS: A 20-year-old female presented to the ED with diffuse abdominal pain, severe hypertension (190/121), and acute kidney injury (AKI) (Cr 2.4, GFR 38). At presentation, management of hypertension required intravenous hydralazine and adequate pain control. The workup included an abdominal CT that revealed a large 25×18×12-cm cystic mass. The mass was suspected to have a significant mass-effect on adjacent structures that caused bilateral hydroureteronephrosis secondary to distal ureteral compression. Management of this case began with the placement of bilateral nephrostomy tubes to improve renal function. The pelvic mass was removed with a minimally invasive robotic approach. The patient had an uneventful postoperative course with normalization of blood pressure and resolution of the AKI. Pathology confirmed the diagnosis of endometriosis. Prior to the removal of nephrostomy tubes, a nephrostogram was performed, which demonstrated appropriate drainage bilaterally. At 1 year follow-up, the patient was asymptomatic and was able to conceive. This case report was IRB-exempt. CONCLUSION: A multidisciplinary approach to the management of endometriosis is often warranted as it may affect organs outside of the reproductive system. In this case, the etiology of hypertension is believed to be due to mass effect of the cyst on the renal arteries. Low renal perfusion activates the renin–angiotensin–aldosterone system, releasing Angiotensin II and aldosterone, causing systemic vasoconstriction and secondary hypertension. In this case, a minimally invasive approach to remove the mass and ureterolysis resulted in the resolution of the pelvic pain, AKI, and normalization of blood pressure.

Addressing the enigma of treating heart failure with preserved ejection fraction with P2X3 receptor antagonism

Heart failure with preserved ejection fraction (HFpEF) is a major health burden and a primary cause of death globally, yet there remains no curative treatment. Previous studies have indicated an important role for P2X3 receptors (P2X3R) in mediating high levels of sympathetic drive in hypertension (1). Given the high sympathetic drive in HFpEF(2), we investigated whether P2X3R antagonism would improve this condition. We tested the hypotheses that in HFpEF, P2X3R activation causes high levels of blood pressure and excessive vasoconstriction in the hindlimb vasculature during exercise. Following unilateral renal artery clipping, an ovine model of HFpEF was established in female sheep displaying hypertension and diastolic dysfunction. A sham-operated group acted as a control. Mean arterial pressure (MAP), heart rate (HR), and hindlimb blood flow (HLBF) were recorded before and during treadmill exercise, and the effect of either a P2X3R antagonist (L227, 10mg/kg) or vehicle was assessed. The clipping of one renal artery increased MAP (91±5 vs. 131±6, p≤0.05). The administration of the P2X3R antagonist reduced both MAP (-6±7 mmHg, p≤0.05) and HR (-6±6 bpm, p&lt;0.05) in HFpEF sheep but no effect in sham-operated animals. HLBF during exercise was attenuated in the HFpEF model compared to sham-operated sheep (an increase of 2±1 vs. 4±2 L/min, respectively, p&lt;0.05). Importantly, P2X3R blockade improved the change in HLBF during exercise from 1±0.1 to 2±0.4 L/min in HFpEF sheep, but there was no change in the sham-operated animals. There was no change in the MAP or HR response to the exercise with the P2X3R blockade. P2X3R plays a role in the aetiology of hypertension and in the attenuation of HLBF responses during exercise in HFpEF. P2X3R antagonism may provide a novel target to alleviate symptoms of HFpEF and improve exercise tolerance through increased HLBF. 1. Pijacka W, Moraes DJ, Ratcliffe LE, Nightingale AK, Hart EC, da Silva MP, Machado BH, McBryde FD, Abdala AP, Ford AP and Paton JFR. Purinergic receptors in the carotid body as a new drug target for controlling hypertension. Nature medicine 22: 1151-1159, 2016. 2. Seravalle G, Quarti-Trevano F, Dell’Oro R, Gronda E, Spaziani D, Facchetti R, Cuspidi C, Mancia G, and Grassi G. Sympathetic and baroreflex alterations in congestive heart failure with preserved, midrange and reduced ejection fraction. Journal of Hypertension 37: 443-448, 2019. Health Research Council of New Zealand and Sidney Taylor Trust. 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.

Systemic Hormonal Unloading (SHU) in Secondary Hypertension: Addressing the Long-Term Adverse Cardiovascular Outcomes

Excess hormone production from adrenal tumors caused by primary hyperaldosteronism or pheochromocytoma are common etiologies for secondary hypertension. Studies have shown that sustained long-term circulating hormones in excess affect the blood vessels and cardiac structures. Inflammation of cardiomyocytes leads to fibrosis and eventual cardiomyopathy and is clinically presented as arrhythmia, nonfatal myocardial infarction, heart failure, or even death. The tissue changes and/or impaired cardiac function are reversible if early diagnosis and removal of the adrenal tumor by unilateral adrenalectomy is done. However, the condition becomes challenging if the adrenal lesions are bilateral. This article introduces the concept of systemic hormonal unloading and will discuss the philosophy of quality of life in managing bilateral adrenal disease. Keywords: systemic hormonal unloading, secondary hypertension, primary hyperaldosteronism, pheochromocytoma, bilateral adrenal venous sampling, cardiovascular adverse outcomes, quality of life

Immune mechanisms in the pathophysiology of hypertension.

Hypertension is a leading risk factor for morbidity and mortality worldwide. Despite current anti-hypertensive therapies, most individuals with hypertension fail to achieve adequate blood pressure control. Moreover, even with adequate control, a residual risk of cardiovascular events and associated organ damage remains. These findings suggest that current treatment modalities are not addressing a key element of the underlying pathology. Emerging evidence implicates immune cells as key mediators in the development and progression of hypertension. In this Review, we discuss our current understanding of the diverse roles of innate and adaptive immune cells in hypertension, highlighting key findings from human and rodent studies. We explore mechanisms by which these immune cells promote hypertensive pathophysiology, shedding light on their multifaceted involvement. In addition, we highlight advances in our understanding of autoimmunity, HIV and immune checkpoints that provide valuable insight into mechanisms of chronic and dysregulated inflammation in hypertension.