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 mesenteric 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.day-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 baseline PP in all groups except 30-mo-old rats, suggesting that 1) baseline tone is maintained by the release of E vasoconstrictor factor(s) and 2) this mechanism is impaired in 30-mo-old rats. The muscarinic agonist, carbachol, antagonized vasoconstriction produced by norepinephrine (NE) in the presence of E. This mechanism was impaired in 30-mo-old rats. NE vasoconstriction increased following disruption of E, suggesting that NE release of endothelium-derived relaxing factor attenuates vasoconstriction. This mechanism was impaired in 30-mo-old rats. Chronic ACEI postponed the age-related decrease in E function, possibly due to a direct effect, or an indirect effect via the prolonged hypotensive action of such treatment.
Atkinson
J
J
Laboratoire de Pharmacologie Cardio-Vasculaire, Faculté de Pharmacie de l'Université de Nancy, France.
Tatchum-Talom
R
R
Corman
B
B
D000375:Aging / Q000187:drug effects*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D010477:Perfusion; D020913:Perindopril; D011189:Potassium Chloride / Q000494:pharmacology; D011312:Pressure; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D007211:Indoles; D009599:Nitroprusside; D011189:Potassium Chloride; D002217:Carbachol; D009638:Norepinephrine; D020913:Perindopril