Why the study?
The potential role of sex differences in blood pressure responses to renin-angiotensin-aldosterone system blockade, including mineralocorticoid receptor antagonism, in obesity was unclear.
Does MR antagonism alone or combined with AT1R blockade reduce blood pressure in male and female obese Zucker rats?
Does MR antagonism alone or combined with AT1R blockade reduce blood pressure in male and female obese Zucker rats?
Combined AT1R and MR blockade reduces blood pressure in obese Zucker rats with significant sex differences, while MR blockade alone has no major effect.
Sex differences in BP response to AT1R blockade but limited MR role in obese rats are hypothesis-generating; human studies needed before clinical translation.
BACKGROUND: Previous studies suggest that obesity-induced hypertension in females, but not males, is due to leptin-mediated stimulation of aldosterone secretion and subsequent activation of the mineralocorticoid receptor (MR). Although angiotensin II type 1 receptor (AT1R) antagonism lowers blood pressure (BP) in male obese Zucker rats (OZR), which have defective leptin signaling, the potential role of sex differences in BP responses to renin-angiotensin-aldosterone system blockade, including MR antagonism, in obesity is still unclear. We tested the cardiovascular effects of MR antagonism, alone or in combination with AT1R blockade in male and female OZR (n = 5/sex) and lean Zucker rats (n = 7/sex). METHODS: BP and heart rate (HR) were measured by telemetry 24 hour/day. After a 6-day control period, spironolactone (40 mg/kg/day) was given for 10 days followed by a 7-day combined treatment with losartan (20 mg/kg/day), and followed by 6-day post-treatment recovery period. RESULTS: Compared with lean rats, OZR were hypertensive (mean arterial pressure: 115 ± 4 vs. 104 ± 2 and 111 ± 1 vs. 100 ± 3 mm Hg for males and females) and had lower HR (355 ± 9 vs. 393 ± 7 and 367 ± 10 vs. 412 ± 13 bpm). MR blockade alone did not alter BP or HR in lean or obese male and female Zucker rats, whereas combined treatment reduced BP in obese and lean rats by 31 ± 3 vs. 21 ± 1 and 8 ± 1 vs. 5 ± 1 mm Hg in males and females, respectively. No changes were observed in HR. CONCLUSIONS: These results suggest that there are important sex differences in BP responses to chronic AT1R blockade but no major involvement of MR activation in BP regulation in OZR.
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Carmo et al. (2020) studied this question.
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