Inhibition of converting enzyme prevents the age-related decline in endothelium-dependent hyperpolarization

The studies summarized here tested whether or not endothelium-dependent hyperpolarization and relaxation caused by endothelium-derived hyperpolarizing factor (EDHF) decline with aging, and, if so, whether or not chronic treatment with a converting enzyme inhibitor improves the age-related endothelial dysfunction, EDHF-mediated hyperpolarization and relaxation were examined in mesenteric arteries obtained from 3-, 6-. 12-, and 24-month-old, normotensive Wistar Kyoto rats (WKY). In addition. a number of the rats were treated for 3 months with either enalapril or a combination of hydralazine and hydrochlorothiazide from 9- to 12-month-old. EDHF-mediated hyperpolarization to acetylcholine was impaired in arteries from 12- and 24-month-old rats compared with younger rats, with the response tending to be further impaired in 24-month-old rats than in 12-month-old rats. EDHF-mediated relaxations also exhibited an age-related impairment. The EDHF-mediated hyperpolarizations and relaxations in 12-month-old rats improved by 3 months of treatment with enalapril but not with a combination of hydralazine and hydrochlorothiazide, despite a similar reduction in blood pressure by both treatments, These findings suggest that: (a) endothelium-dependent hyperpolarization and relaxation via EDHF decline with aging in rat arteries, and M chronic treatment with converting enzyme inhibitor enalapril, but not a conventional therapy with vasodilators and diuretics, improves the age-related impairment of EDHF-mediated responses. These findings raise the possibility that blockade of the renin-angiotensin system might prevent or retard the age-related endothelial dysfunction.