Sex-related differences in the response of spontaneously hypertensive rats to angiotensin-converting enzyme inhibitor.
We have compared the endothelium-dependent responses of thoracic aortic rings obtained from age-matched male and female SHR in order to explore gender differences in the effectiveness of antihypertensive drug therapy in correcting the endothelial dysfunction found in these animals. For this, concentration-effect curves to acetylcholine and sodium nitroprusside were obtained using aortic rings with and without endothelium 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 remained normal during the remainder of the treatment period (15 d). However, enalapril was not effective in restoring a normal blood pressure in all of the male and female SHR. Female SHR were more responsive to enalapril after both acute and chronic treatment (70% of the females and 45% of the males became normotensive). Enalapril corrected the decreased response to acetylcholine in male but not in female SHR. An increased sensitivity to sodium nitroprusside, an endothelium-independent vasodilator, was observed after acute or chronic treatment with enalapril in aortic rings with endothelium from male SHR. Indomethacin restored the decreased response to acetylcholine in aortic rings from enalapril-treated females and potentiated the response to acetylcholine in aortic rings from treated male SHR. We conclude that: a) there are significant differences in the responses of male and female SHR to enalapril, b) the imbalance in endothelium-dependent relaxing and contracting factors in SHR is corrected by enalapril in male but not in female SHR, c) correction of the endothelial dysfunction probably occurs independently of the normalization of blood pressure levels and appears to be gender-dependent.
Nigro
D
D
Department of Pharmacology, University of Säo Paulo, Brazil.
Fortes
Z B
ZB
Scivoletto
R
R
Barbeiro
H V
HV
Carvalho
M H
MH
D000109:Acetylcholine / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001011:Aorta; D001794:Blood Pressure / Q000187:drug effects; D004656:Enalapril / Q000494:pharmacology*; D004727:Endothelium / Q000187:drug effects*; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR / Q000502:physiology*; D012737:Sex Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D009599:Nitroprusside; D004656:Enalapril; D000109:Acetylcholine