Sexual dimorphism in the response of thoracic aorta from SHRs to losartan

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.