ABSTRACT
The studies summarized here tested whether or not endothelium-dependent hyper polarization and relaxation caused by endothelium-derived hyperpolarizing factor ( E D H F ) decline with aging, and, i f so, whether or not chronic treatment with a con verting enzyme inhibitor improves the age-related endothelial dysfunction. E D H F - mediated hyperpolarization and relaxation were examined in mesenteric arteries obtained from 3-, 6-, 12-, and 24-month-old, normotensive Wistar Kyoto rats ( W K Y ) . 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. E D H F - 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) endo thelium-dependent hyperpolarization and relaxation via E D H F decline with aging in rat arteries; and (b) 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.
