In spontaneously hypertensive rats, females are more dependent on ANG (1-7) to mediate the blood pressure-lowering effects of low-dose AT1 receptor blockade with candesartan than males.
Does ANG (1-7) contribute more to the blood pressure-lowering effects of candesartan in female spontaneously hypertensive rats compared to males?
In spontaneously hypertensive rats, females are more dependent on ANG (1-7) to mediate the blood pressure-lowering and renoprotective effects of low-dose AT1 receptor blockade than males.
Absolute Event Rate: 115% vs 129%
p-value: p=<0.05
ANG (1-7) contributes to the blood pressure (BP)-lowering effect of angiotensin receptor blockers (ARBs) in male experimental animals. Females have greater ANG (1-7) concentrations than males; however, the contribution of ANG (1-7) to ARB-mediated decreases in BP in females is unknown. The current study tested the hypothesis that female spontaneously hypertensive rats (SHR) have a larger ANG (1-7) contribution to the BP-lowering effects of the ARB candesartan than male SHR. Twelve-week-old male and female SHR were randomized to receive candesartan (0.5 mg·kg −1 ·day −1 ; 7 days), candesartan plus ANG II (200 ng·kg −1 ·min −1 ; 7 days), the ANG (1-7) antagonist A-779 (48 μg·kg −1 ·h −1 ) plus candesartan and ANG II. Candesartan decreased basal BP in males and females (baseline vs. candesartan: 142 ± 2 vs. 122 ± 3 and 129 ± 1 vs. 115 ± 1 mmHg, respectively; P < 0.05); however, the decrease was greater in males. ANG II increased BP in males in the presence of candesartan (149 ± 2 mmHg; P < 0.05); candesartan blocked ANG II-induced increases in BP in females (116 ± 1 mmHg). Pretreatment with A-779 abolished candesartan-mediated decreases in BP in females, but not males. A-779 also exacerbated ANG II-induced proteinuria (26 ± 6 vs. 77 ± 11 μg·kg −1 ·day −1 , respectively; P < 0.05) and nephrinuria (20 ± 5 vs. 202 ± 58 μg·kg −1 ·day −1 , respectively; P < 0.05) in candesartan-treated female SHR, with no effect in males. In conclusion, females are more sensitive to the BP-lowering effect of ARBs during ANG II infusion, whereas males are more sensitive under basal conditions. In addition, ANG (1-7) has a greater contribution to ARB-mediated decreases in BP, protein, and nephrin excretion in females relative to males.
Zimmerman et al. (Thu,) conducted a other in Hypertension (Spontaneously Hypertensive Rats). Candesartan with or without ANG II and A-779 vs. Baseline and Male SHR was evaluated on Basal blood pressure in females (mmHg) (p=<0.05). In spontaneously hypertensive rats, females are more dependent on ANG (1-7) to mediate the blood pressure-lowering effects of low-dose AT1 receptor blockade with candesartan than males.