Effect of in vitro administration of captopril on vascular reactivity of rat aorta.
The effect of acute administration of captopril, an angiotensin converting enzyme inhibitor, on vascular responses of rings of rat aortic smooth muscle was tested in vitro. Dose-response curves for various vasoactive agents were obtained before and after exposure to captopril (2 x 10(-4) M) for 30 minutes. In the presence of captopril, contractile responses to angiotensin I (5 x 10(-10) to 5 x 10(-8) M) were attenuated significantly, probably as a result of decreased local conversion of angiotensin I to angiotensin II. Contractile responses to angiotensin II (10(-11) to 5 x 10(-9) M) were not affected by captopril. All responses to norepinephrine (10(-9) to 10(-4) M) and phenylephrine (10(-8) to 10(-4) M) were attenuated significantly from control in the presence of captopril. In the presence of the alpha-adrenergic antagonist, phentolamine, captopril did not affect either the contractile responses to KCl (30 to 100 mM) or the isoproterenol-induced (10(-8) to 10(-5) M) relaxation of KCl-depolarized tissue. These results suggest that captopril decreased vascular responsiveness to alpha-adrenergic agonists but not to beta-adrenergic agonists. Low concentrations of bradykinin (10(-10) to 10(-8) M) induced contraction in KCl-depolarized tissue while higher concentrations (10(-7) and 10(-6) M) induced relaxation. In the presence of captopril, relaxation occurred at all concentrations of bradykinin (10(-10) to 10(-6) M), probably as a result of decreased degradation of the bradykinin. These data suggest depression of alpha-adrenergic responsiveness in vascular smooth muscle as another potential antihypertensive action of captopril.
D000803:Angiotensin I / Q000037:antagonists & inhibitors; D000804:Angiotensin II / Q000037:antagonists & inhibitors; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001920:Bradykinin / Q000037:antagonists & inhibitors; D002216:Captopril / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007545:Isoproterenol / Q000037:antagonists & inhibitors; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000037:antagonists & inhibitors; D010656:Phenylephrine / Q000037:antagonists & inhibitors; D011189:Potassium Chloride / Q000037:antagonists & inhibitors; D011392:Proline / Q000031:analogs & derivatives*; D051381:Rats; D011919:Rats, Inbred Strains; D014661:Vasoconstriction / Q000187:drug effects
D000804:Angiotensin II; D010656:Phenylephrine; D011189:Potassium Chloride; D000803:Angiotensin I; D011392:Proline; D002216:Captopril; D007545:Isoproterenol; D001920:Bradykinin; D009638:Norepinephrine