SEX-RELATED DIFFERENCES IN THE RESPONSE OF SPONTANEOUSLY HYPERTENSIVERATS TO ANGIOTENSIN-CONVERTING ENZYME-INHIBITOR

We have compared the endothelium-dependent responses of thoracic aorti c rings obtained from age-matched male and female SHR in order to expl ore gender differences in the effectiveness of antihypertensive drug t herapy in correcting the endothelial dysfunction found in these animal s, For this, concentration-effect curves to acetylcholine and sodium n itroprusside mere obtained using aortic rings with and without endothe lium isolated from male and female rats which had or had not been pre- treated with enalapril for 72 h (acute) or 15 d (chronic), The maximal responses achieved and the EC50s were determined, The blood pressure of male and female spontaneously hypertensive rats (SHR) decreased to normal levels within 72 h of initiating treatment with enalapril and r emained normal during the remainder of the treatment period (15 d), Ho wever, enalapril was not effective in restoring a normal brood pressur e in all of the male and female SHR, Female SHR were more responsive t o enalapril after both acute and chronic treatment (70% of the females and 45% of the males became normotensive). Enalapril corrected the de creased response to acetylcholine in male but not in female SHR, An in creased sensitivity to sodium nitroprusside, an endothelium-independen t vasodilator, was observed after acute or chronic treatment with enal april in aortic rings with endothelium from male SHR, Indomethacin res tored the decreased response to acetylcholine in aortic rings from ena lapril-treated females and potentiated the response to acetylcholine i n aortic rings from treated male SHR, We conclude that: a) there are s ignificant differences in the responses of male and female SHR to enal april, b) the imbalance in endothelium-dependent relaxing and contract ing factors in SHR is corrected by enalapril in male but not in female SHR, c) correction of the endothelial dysfunction probably occurs ind ependently of the normalization of blood pressure levels and appears t o be gender-dependent.