Influence of enalapril on the endothelial function of DOCA-salt hypertensive rats

In the present study, we investigated whether the correction of endothelial dysfunction can be independent of the normalization of high blued pressure levels by enalapril in deoxycorticosterone (DOCA-salt) hypertensive rats. Aorta morphology and the response of aortas with (E+) and without (E-) endo thelium to noradrenaline, acetylcholine, and sodium nitroprusside were stud ied. DOCA-salt hypertensive and normotensive (control) rats were or were no t treated with enalapril (5 mg/day/rat in the drinking fluid) for 1, 7, or 15 days. Blood pressure was measured before and after 1, 3, 7, and 15 days of enalapril treatment. Enalapril normalized the high blood pressure levels in 50% (responders) of the hypertensive rats after 3 to as many as 15 days but not after 1 day of treatment, Initial blood pressure levels were not d ifferent between responders and nonresponders. Blood pressure levels of nor motensive control rats were not altered by enalapril treatment. The tunica media of aortas of DOCA-salt hypertensive rats treated or not treated with enalapril for 15 days was thicker than aortas from normotensive rats. Enala pril corrected the reduced response to acetylcholine observed in aorta from hypertensive rats fr-om the first day of treatment. This treatment rendere d aortas from normotensive control rats more sensitive (lower EC50) to acet ylcholine without a change in the maximal responses. The responses to sodiu m nitroprusside, a nitric oxide donor, were unaltered in aorta E+ or E- fro m control and hypertensive rats before and after enalapril treatment. Enala pril did not correct the increased responses to noradrenaline observed in a orta E+ of hypertensive rats. These results suggest that the high blood pre ssure in DOCA-salt hypertension is not correlated with the altered response to endothelium-dependent agents (either dilator or constrictors). The endo tfielinm-dependent vasodilation by antihypertensive agents can be corrected independently of normalization of blood pressure levels or the vascular mo rphology. (C) 2000 Elsevier Science Inc. All rights reserved.