Female rats were protected from hypertensive renal and cardiac injury after renal artery clipping, associated with an increase in the intratubular nonclassic RAS and a decreased AT1/AT2 receptor ratio.
Female rats are protected from renovascular hypertension-induced injury via estrogen-mediated upregulation of the nonclassic intratubular renin-angiotensin system.
The intratubular renin-angiotensin system (RAS) is thought to play an essential role in hypertensive renal disease, but information regarding sex-related differences in this system is limited. The present study investigated sex differences in the intratubular RAS in two-kidney, one-clip (2K1C) rats. A 2.5-mm clip was placed on the left renal artery of Sprague-Dawley rats, and rats were euthanized 3 or 5 wk after the operation. Systolic blood pressure increased in 2K1C rats in both sexes but was significantly higher in male rats than in female rats, and an antihypertensive effect was not observed in 2K1C ovariectomized (OVX) female rats. Compared with male 2K1C rats, intratubular angiotensin-converting enzyme (ACE) and ANG II were repressed, and intratubular ACE2, angiotensin (1-7), and Mas receptor were increased in both kidneys in female 2K1C rats 5 wk after surgery. Comparison with male and female rats and intratubular mRNA levels of ACE and ANG II type 1 receptor were augmented in OVX female rats, regardless of the clipping surgery 3 wk postoperation. ANG II type 2 receptor was upregulated in female rats with or without OVX; thus, the ANG II type 1-to-type 2 receptor ratio was higher in male rats than in female rats. In conclusion, female rats were protected from hypertensive renal and cardiac injury after renal artery clipping. An increase in the intratubular nonclassic RAS ACE2/angiotensin (1-7)/Mas receptor and a decrease in the ANG II type 1-to-type 2 receptor ratio could limit the adverse effects of the classic RAS during renovascular hypertension in female rats, and estrogen is suggested to play a primary role in the regulation of intratubular RAS components.
Lee et al. (Wed,) conducted a other in Renovascular hypertension. Female sex (estrogen presence) vs. Male rats and ovariectomized (OVX) female rats was evaluated on Intratubular renin-angiotensin system components and blood pressure. Female rats were protected from hypertensive renal and cardiac injury after renal artery clipping, associated with an increase in the intratubular nonclassic RAS and a decreased AT1/AT2 receptor ratio.