EFFECT OF CHRONIC ANG I-CONVERTING ENZYME-INHIBITION ON AGING PROCESSES .III. ENDOTHELIAL FUNCTION OF MESENTERIC ARTERIAL BED OF RAT

Age-related changes in endothelial (E) function were studied in mesent eric arterial bed (MAB) preparations removed from male, normotensive, WAG/Rij rats. At the age of 6 mo, one-half of the animals was assigned to chronic treatment with a hypotensive dose of an angiotensin I (ANG I)-converting enzyme inhibitor (ACEI; perindopril, 1 mg . kg(-1) . da y(-1) po). Animals were killed at 6, 12, 24, or 30 mo of age; the MAB was perfused in vitro, perfusion pressure (PP) being taken as an index of arteriolar tone. Disruption of E function produced a fall in basel ine PP in all groups except 30-mo-old rats, suggesting that 1) baselin e tone is maintained by the release of E vasoconstrictor factor(s) and 2) this mechanism is impaired in 30-mo-old rats. The muscarinic agoni st, carbachol, antagonized vasoconstriction produced by norepinephrine (NE) in the presence of E. This mechanism was impaired in 30-mo-old r ats. NE vasoconstriction increased following disruption of E, suggesti ng that NE release of endothelium-derived relaxing factor attenuates v asoconstriction. This mechanism was impaired in 30-mo-old rats. Chroni c ACEI postponed the age-related decrease in E function, possibly due to a direct effect, or an indirect effect via the prolonged hypotensiv e action of such treatment.