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 order to explore gender differences in the normalization of the high blood pressure by antihypertensive drug therapy and in the correction of the endothelial dysfunction found in these animals. 2. Concentration-effect curves to acetylcholine (ACh) and sodium nitroprusside (SNP) were obtained using aortic rings isolated from male and female rats pretreated or not with losartan for 24 h or 15 d. The responses achieved and the EC50s 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 within 24 h of initiating the treatment and remained normal during the remainder of the treatment period (15 d). 4. Losartan (15 d) corrected the decreased response to ACh in male and female SHR, independently of the normalization of blood pressure in male SHR. 5. An increased sensitivity to SNP was observed after chronic treatment with losartan in aortic rings from female SHR. 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 to ACh observed in male and female is corrected after sustained (15 d) reduction of high blood pressure. In female but not in male SHR, correction seems to involve an increased sensitivity of the smooth muscle to nitric oxide.
Silva-Antonialli
M M
MM
Laboratory of Hypertension, Department of Pharmacology, Institute of Biomedical Science, University of São Paulo, Av Prof Lineu Prestes, 1524, 05008-900, SP, São Paulo, Brazil.
Fortes
Z B
ZB
Carvalho
M H
MH
Scivoletto
R
R
Nigro
D
D
D000109:Acetylcholine / Q000627:therapeutic use; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001013:Aorta, Thoracic / Q000737:chemistry / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects; D005260:Female; D006973:Hypertension / Q000628:therapy*; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D012680:Sensitivity and Specificity; D012727:Sex Characteristics; D014665:Vasodilator Agents / Q000627:therapeutic use
D000959:Antihypertensive Agents; D014665:Vasodilator Agents; D019808:Losartan; D000109:Acetylcholine