Sex influences the effect of body mass index on the vascular response to angiotensin II in humans

Abstract

Objective: Sex influences the cardiorenal risk associated with body mass index (BMI). The role of the renin-angiotensin-aldosterone system in adiposity-mediated cardiorenal risk profiles in healthy, nonobese men and women was investigated. Methods: Systemic and renal hemodynamic responses to angiotensin-II (AngII) as a function of BMI, waist and hip circumference, waist-hip ratio, as well as fat and lean mass were measured in 18 men and 25 women in high-salt balance, stratified by BMI (<25 kg/m 2 (ideal body weight (IBW)) vs. 25 kg/m 2 overweight)). Results: In men (n 5 7, BMI 23 6 1 kg/m 2 ) and women (n 5 14, BMI 22 6 2 kg/m 2 ) of IBW, BMI was not associated with the systolic blood pressure (SBP) response to AngII. In contrast, overweight men (n 5 11, 29 6 2 kg/m 2 ) demonstrated a progressively more blunted vasoconstrictor SBP response to AngII challenge as BMI increased (P 5 0.007), even after adjustment for covariates. Women maintained the same relationship between BMI and the SBP response to AngII irrespective of weight status (P 5 0.2, IBW vs. overweight women). Compared to BMI, other adiposity measures showed similar associations to systemic AngII responsiveness in men but not in women. Increasing BMI was associated with a blunted renovasoconstrictor response to AngII in all subjects, but was more pronounced in men. Conclusion: Sex influences the effect of adiposity on vascular angiotensin-responsiveness.

Nocturnal Hypoxemia Severity and Renin–Angiotensin System Activity in Obstructive Sleep Apnea

“…Our previous work has demonstrated a decrease in ERPF of 182±98 (mean±SD) and 320±212ml/min/1.73m 2 (mean±SD, mean of male and female responses) in response to AngII infusion on a high-salt diet in moderately hypoxic OSA patients(4) and healthy overweight controls (18) respectively. Based on this data and anticipating a 40% difference in the RPF response between the severe hypoxemia group and the obese control group, we estimated that 12 subjects would be required in each group with a two-sided alpha of 0.05 and 90% power.…”

“…As is common, the OSA subjects in this study were obese (17). To control for any effects of increased BMI on renal hemodynamics or renal RAS activity, (18,19) we included a comparably obese control group. Despite our careful study design, the severe hypoxemia group differed in terms of ethnicity, BMI and sex, all of which may influence renal RAS activity.…”

“…Obesity is common in patients with OSA (17) and increased body mass index (BMI) can have an independent effect on the renal RAS (18,19). We performed a study that was designed to address both of these limitations.…”

Serum uric acid level, blood pressure, and vascular angiotensin II responsiveness in healthy men and women

“…; Zalucky et al. ). Our findings of an association between increased uric acid levels and an increasingly vasoconstrictor response to AngII in women are therefore a reflection of lower local tissue–AngII concentrations and tissue–RAS activity.…”

“…UA stimulates Ang-II production in vascular smooth muscle cells, suggesting that UA causes cardiovascular disorders by stimulating the vascular RAS (Corry et al 2008). A more sensitive vascular response to Ang-II has been interpreted as consistent with down-regulated RAS activity (Shoback et al 1983a;Price et al 2002;Ahmed et al 2004;Miller et al 2006;Cherney et al 2008;Forman et al 2010;Vaidya et al 2012;Nicholl et al 2014;Zalucky et al 2014). Our findings of an association between increased uric acid levels and an increasingly vasoconstrictor response to AngII in women are therefore a reflection of lower local tissue-AngII concentrations and tissue-RAS activity.…”