Sex differences in cardiovascular actions of the renin–angiotensin system

Background: The number of the patients with heart failure with preserved ejection fraction (HFpEF) has been rapidly increasing worldwide. However, sex differences in patients with HFpEF remain to be elucidated. Methods and Results: We examined sex differences in 3,124 consecutive patients with HFpEF (EF≥50%, mean 69.4years, 34.7% female) registered in our Chronic Heart Failure Analysis and Registry in the Tohoku District-2 (CHART-2) Study (N=10,219). Female patients, as compared with male patients, were characterized by higher age (72 vs. 68 years, P<0.01), higher LVEF (67 vs. 64%, P<0.01), higher heart rate (74 vs. 70bpm, PNYHA class III (14.1 vs. 7.0%, P<0.01), higher BNP levels (106 vs. 73pg/mL, P<0.01), lower prevalence of coronary artery disease (30 vs. 53%, P<0.01) and lower prescription rates of renin angiotensin system inhibitors (64.7 vs. 71.8%, P<0.01) and beta-blockers (37.8 vs. 43.9%, P<0.01). During the median 3.2-year follow-up, 147 female patients and 245 males died. Although there was no sex difference in all-cause mortality (13.6 vs. 12.0%, P=0.11), female patients more frequently died due to cardiovascular causes (53.7 vs. 39.2%, hazard ratio (HR): 1.62, 95% CI 1.20-2.18, P<0.01), and experienced more HF admissions (12.6 vs. 9.8%, HR: 1.35, 95% CI 1.08-1.68, P<0.01). Use of beta-blockers or renin-angiotensin system inhibitors was not associated with decreased incidence of death or HF admission in both sexes. In contrast, use of statins was associated with reduced incidence of all-cause death in both sexes (males and females; adjusted HR, 0.59 and 0.57; 95% CI 0.46-0.77 and 0.47-0.70, respectively, both P<0.01) and was also associated with reduced incidence of HF admission in males (adjusted HR: 0.67, 95%CI 0.53-0.85, P<0.01) but not in females (adjusted HR: 0.83, 95% CI 0.63-1.10, P=0.19). Conclusions: As compared with males, female patients with HFpEF were characterized by severer condition of HF and increased risk of cardiovascular death and HF admission. Although statin use was equally associated with improved mortality in both sexes, female patients with HFpEF may benefit from statins less than males in terms of reduction of HF admission.

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Fetal and postnatal zinc restriction: sex differences in the renal renin-angiotensin system of newborn and adult Wistar rats

The Journal of Nutritional Biochemistry ◽

10.1016/j.jnutbio.2020.108385 ◽

2020 ◽

Vol 81 ◽

pp. 108385 ◽

Cited By ~ 1

Author(s):

María Natalia Gobetto ◽

Facundo Mendes Garrido Abregú ◽

Carolina Caniffi ◽

Luciana Veiras ◽

Rosana Elesgaray ◽

...

Keyword(s):

Sex Differences ◽

Wistar Rats ◽

Renin Angiotensin System ◽

Angiotensin System ◽

Renin Angiotensin

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Angiotensin-(1-7): Translational Avenues in Cardiovascular Control

American Journal of Hypertension ◽

10.1093/ajh/hpz146 ◽

2019 ◽

Vol 32 (12) ◽

pp. 1133-1142 ◽

Cited By ~ 5

Author(s):

Daniela Medina ◽

Amy C Arnold

Keyword(s):

Blood Pressure ◽

Angiotensin Ii ◽

Current Knowledge ◽

Renin Angiotensin System ◽

Cardiovascular Control ◽

Biologically Active ◽

Global Public Health ◽

Angiotensin System ◽

Renin Angiotensin ◽

Cardiovascular Actions

Abstract Despite decades of research and numerous treatment approaches, hypertension and cardiovascular disease remain leading global public health problems. A major contributor to regulation of blood pressure, and the development of hypertension, is the renin-angiotensin system. Of particular concern, uncontrolled activation of angiotensin II contributes to hypertension and associated cardiovascular risk, with antihypertensive therapies currently available to block the formation and deleterious actions of this hormone. More recently, angiotensin-(1–7) has emerged as a biologically active intermediate of the vasodilatory arm of the renin-angiotensin system. This hormone antagonizes angiotensin II actions as well as offers antihypertensive, antihypertrophic, antiatherogenic, antiarrhythmogenic, antifibrotic and antithrombotic properties. Angiotensin-(1–7) elicits beneficial cardiovascular actions through mas G protein-coupled receptors, which are found in numerous tissues pivotal to control of blood pressure including the brain, heart, kidneys, and vasculature. Despite accumulating evidence for favorable effects of angiotensin-(1–7) in animal models, there is a paucity of clinical studies and pharmacokinetic limitations, thus limiting the development of therapeutic agents to better understand cardiovascular actions of this vasodilatory peptide hormone in humans. This review highlights current knowledge on the role of angiotensin-(1–7) in cardiovascular control, with an emphasis on significant animal, human, and therapeutic research efforts.

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Sex differences in the metabolic effects of the renin-angiotensin system

Biology of Sex Differences ◽

10.1186/s13293-019-0247-5 ◽

2019 ◽

Vol 10 (1) ◽

Cited By ~ 19

Author(s):

Melissa C. White ◽

Rebecca Fleeman ◽

Amy C. Arnold

Keyword(s):

Sex Differences ◽

Renin Angiotensin System ◽

Metabolic Effects ◽

Angiotensin System ◽

Renin Angiotensin

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Sex-Differences in Initiation of Renin-Angiotensin System Inhibitors in Patients with Type 2 Diabetes and Albuminuria

SSRN Electronic Journal ◽

10.2139/ssrn.3840085 ◽

2021 ◽

Author(s):

Morten Malmborg ◽

Nicholas Carlson ◽

Michelle D. S. Schmiegelow ◽

Thomas Gerds ◽

Morton Schou ◽

...

Keyword(s):

Type 2 Diabetes ◽

Sex Differences ◽

Renin Angiotensin System ◽

Angiotensin System ◽

Renin Angiotensin

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Sex differences in renal hemodynamics and renin-angiotensin system activity post-CPAP therapy in humans with obstructive sleep apnea

AJP Renal Physiology ◽

10.1152/ajprenal.00290.2019 ◽

2020 ◽

Vol 318 (1) ◽

pp. F25-F34 ◽

Cited By ~ 2

Author(s):

David D. M. Nicholl ◽

Patrick J. Hanly ◽

Ann A. Zalucky ◽

George B. Handley ◽

Darlene Y. Sola ◽

...

Keyword(s):

Obstructive Sleep Apnea ◽

Sex Differences ◽

Sleep Apnea ◽

Renin Angiotensin System ◽

Renal Hemodynamics ◽

Ang Ii ◽

Cpap Therapy ◽

Angiotensin System ◽

Renin Angiotensin ◽

Obstructive Sleep

Men have faster loss of kidney function and greater renal renin-angiotensin system (RAS) activity compared with women. Obstructive sleep apnea (OSA) is common in chronic kidney disease; the vascular effects of OSA differ by sex, and OSA-associated glomerular hyperfiltration can be reversed by continuous positive airway pressure (CPAP) therapy. We evaluated sex differences in the effect of CPAP on renal hemodynamics and the renal RAS in OSA. Twenty-nine Na+-replete, otherwise healthy study participants with OSA (10 women and 19 men) with nocturnal hypoxemia were studied pre- and post-CPAP (>4 h/night for 4 wk). Renal hemodynamics [renal plasma flow (RPF), glomerular filtration rate (GFR), and filtration fraction(FF)] were measured at baseline and in response to ANG II challenge, as a marker of renal RAS activity, pre- and post-CPAP therapy for 1 mo. In women, CPAP was associated with increased RPF (626 ± 22 vs. 718 ± 43 mL/min, P = 0.007, pre- vs. post-CPAP), maintained GFR (108 ± 2 vs. 105 ± 3 mL/min, P = 0.8), and reduced FF (17.4 ± 0.8% vs. 15.0 ± 0.7%, P = 0.017). In men, CPAP was associated with maintained RPF (710 ± 37 vs. 756 ± 38 mL/min, P = 0.1), maintained GFR (124 ± 8 vs. 113 ± 6 mL/min, P = 0.055), and reduced FF (18.6 ± 1.7% vs. 15.5 ± 1.1%, P = 0.035). Pre-CPAP, there were no sex differences in renal hemodynamic responses to ANG II. CPAP use was associated with a greater renovasoconstrictive response to ANG II in women (RPF at Δ30 min: −100 ± 27 vs. −161 ± 25 mL/min, P = 0.007, and RPF at Δ60 min: −138 ± 27 vs. −206 ± 32 mL/min, P = 0.007) but not men. CPAP use was associated with improved renal hemodynamics in both sexes and downregulated renal RAS activity in women but not men.

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