Key result
Estradiol blunts losartan-promoted renal blood flow response by ~27 percentage points vs. control.
Why the study?
Estrogen replacement therapy and hypertension may influence females' renin-angiotensin system, prompting investigation into their effects on renal blood flow response to Ang II in losartan-treated ovariectomized rats.
Does estradiol or induced hypertension alter the renal blood flow response to Angiotensin II in losartan-treated ovariectomized rats?
Does estradiol or induced hypertension alter the renal blood flow response to Angiotensin II in losartan-treated ovariectomized rats?
Absolute Event Rate: 17.9% vs 45.1%
p-value: p=<0.05
Estradiol supplementation or induced hypertension attenuates the renal blood flow response to Angiotensin II during AT1R blockade with losartan in ovariectomized rats.
Estradiol or hypertension may blunt losartan effects on renal hemodynamics in this rat model; leaves open relevance to human AT1R blockade.
Backgrounds. Estrogen replacement therapy (ERT) and hypertension may influence females’ renin-angiotensin system (RAS) and its components. The angiotensin II (Ang II) type 1 receptor (AT1R) antagonist (losartan) may promote renal blood flow (RBF), and it is widely used in the clinic to control hypertension. The main objective of this study was the effects of estradiol or induced hypertension on RBF response to Ang II in losartan-treated ovariectomized (OVX) rats. Methods. Two groups of OVX rats were treated with placebo (group 1) and estradiol (group 2) for period of four weeks, and another group of OVX rats was subjected to induce hypertension by two-kidney one clip (2K1C) model (group 3). All the groups were subjected to the surgical procedure under anesthesia, and AT1R was blocked by losartan. RBF and renal vascular resistance (RVR) responses to Ang II administration were determined and compared. Results. Mean arterial (MAP) and renal perfusion (RPP) pressures in group 3 and uterus weight (UT) in group 2 were significantly more than other groups ([Formula: see text]). Ang II infusion resulted in dose-related percentage change increase in RBF and decrease in RVR. However, these responses in the OVX-estradiol and OVX-hypertensive rats were significantly lower than in the OVX-control group ([Formula: see text]). For instance, at the dose of 1000 ng/kg/min of Ang II administration, the percentage change of RBF was [Formula: see text], [Formula: see text], and [Formula: see text] in the groups of 1 to 3, respectively. Conclusion. Losartan prescription in some conditions such as hypertension or ERT could worsen RBF and RVR responses to Ang II.
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Choopani et al. (2022) studied Ovariectomized rats with or without induced hypertension (n=18). High-dose estradiol or induced hypertension (2K1C) vs. Placebo (sesame oil) was evaluated on Percentage change of renal blood flow (RBF) in response to 1000 ng/kg/min Angiotensin II administration (p=<0.05). Estradiol administration (17.9%) and 2K1C-induced hypertension (16.7%) significantly attenuated the losartan-promoted renal blood flow response to high-dose angiotensin II infusion compared to control (45.1%).
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