1. We compared the endothelium-dependent responses of thoracic aortic rings
obtained from male and female spontaneously hypertensive rats (SHR) in ord
er to explore gender differences in the normalization of the high blood pre
ssure by antihypertensive drug therapy and in the correction of the endothe
lial dysfunction found in these animals. 2. Concentration-effect curves to
acetylcholine (ACh) and sodium nitroprusside (SNP) were obtained using aort
ic rings isolated from male and female rats pretreated or not with losartan
for 24 h or 15 d. The responses achieved and the ECSDs were determined. 3.
Losartan, AT(1) receptor antagonist, normalized (around 125 mmHg) the high
blood pressure levels in 100% of the females and in 53.3% of males SHR wit
hin 24 h of initiating the treatment and remained normal during the remaind
er of the treatment period (15 d). 4. Losartan (15 d) corrected the decreas
ed response to ACh in male and female SHR, independently of the normalizati
on of blood pressure in male SHR. 5. An increased sensitivity to SNP was ob
served after chronic treatment with losartan in aortic rings from female SH
R. 6. Ridogrel, a TXA(2)/PGH(2) receptor antagonist, restored the decreased
response to ACh in aortic rings from male and female SHR. 7. These results
suggest that there are gender-related differences in the normalization of
the high blood pressure levels by losartan in SHR. The decreased response t
o ACh observed in male and female is corrected after sustained (15 d) reduc
tion of high blood pressure. In female but not in male SHR, correction seem
s to involve an increased sensitivity of the smooth muscle to nitric oxide.
(C) 2001 Elsevier Science Inc. All rights reserved.