Kikta D C, Fregly M J
Hypertension. 1982 Jan-Feb;4(1):118-24. doi: 10.1161/01.hyp.4.1.118.
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.
在体外试验中，检测了血管紧张素转换酶抑制剂卡托普利急性给药对大鼠主动脉平滑肌环血管反应的影响。在暴露于卡托普利（2×10⁻⁴ M）30分钟之前和之后，获得了各种血管活性药物的剂量-反应曲线。在卡托普利存在的情况下，对血管紧张素I（5×10⁻¹⁰至5×10⁻⁸ M）的收缩反应显著减弱，这可能是由于血管紧张素I向血管紧张素II的局部转化减少所致。对血管紧张素II（10⁻¹¹至5×10⁻⁹ M）的收缩反应不受卡托普利影响。在卡托普利存在的情况下，所有对去甲肾上腺素（10⁻⁹至10⁻⁴ M）和去氧肾上腺素（10⁻⁸至10⁻⁴ M）的反应与对照相比均显著减弱。在α-肾上腺素能拮抗剂酚妥拉明存在的情况下，卡托普利既不影响对氯化钾（30至100 mM）的收缩反应，也不影响异丙肾上腺素诱导的（10⁻⁸至10⁻⁵ M）氯化钾去极化组织的舒张。这些结果表明，卡托普利降低了血管对α-肾上腺素能激动剂的反应性，但对β-肾上腺素能激动剂无此作用。低浓度的缓激肽（10⁻¹⁰至¹⁰⁻⁸ M）在氯化钾去极化组织中诱导收缩，而较高浓度（10⁻⁷和10⁻⁶ M）则诱导舒张。在卡托普利存在的情况下，所有浓度的缓激肽（10⁻¹⁰至10⁻⁶ M）均出现舒张，这可能是由于缓激肽降解减少所致。这些数据表明，血管平滑肌中α-肾上腺素能反应性降低是卡托普利的另一种潜在降压作用。
