Frankel R J, Reid I A, Ganong W F
J Pharmacol Exp Ther. 1977 May;201(2):400-5.
The mechanism by which alpha-methyldopa lowers arterial pressure and suppresses renin secretion was investigated in pentobarbital-anesthetized dogs in which changes in renal perfusion pressure were prevented by adjusting a suprarenal aortic clamp. After intravenous alpha-methyldopa (100 mg/kg) mean arterial pressure (MAP) decreased form 127+/-3 to a mean minimum of 107+/-4 mm Hg (P less than .01) and plasma renin activity (PRA) decreased from 20.6+/-4.8 to 10.9+/-1.7 ng/ml/3 hr (P less than .05). Blockade of peripheral dopa decarboxylase with intravenous carbidopa (20 mg/kg) significantly attenuated the hypotensive action of intravenous alpha-methyldopa but MAP still decreased from 145+/-6 to 130+/-5 mm Hg(P less than .001). Intravenous carbidopa completely abolished the fall in PRA produced by intravenous alpha-methyldopa (16.8+/-2.8 to 16.9+/-2.1 ng/ml/3 hr.) Intraventricular carbidopa (3 microng/kg/min) did not block the hypotensive (135+/-8 to 113+/-7 mm Hg, P less than .01) or renin-lowering effect (24.3+/-5 to 13.4+/-3.2 ng/ml/3 hr, P less than .01) of intravenous alpha-methyldopa (0.5 mg/kg decreased MAP from 118 +/- 5 to 104 +/- 5 mm Hg (P less than 0.001) but had no effect on PRA (23.4+/-6 TO 19.4+/-7 NG/ML/3 hr.) Intraventricular alpha-methylnorepinephrine (2 microng/kg) also decreased MAP from 127+/-5 to 112+/-3mm Hg (P less than .006) but again failed to significantly alter PRA (36.1+/-11.8 to 37.2+/-15 ng/ml/3 hr). These results indicate that there is both a central and peripheral component to the antihypertensive effect of alpha-methyldopa in the dog and that the suppression of renin secretion results from a peripheral action of the drug.
在戊巴比妥麻醉的犬中研究了α-甲基多巴降低动脉血压和抑制肾素分泌的机制，通过调节肾上腹主动脉夹来防止肾灌注压的变化。静脉注射α-甲基多巴（100mg/kg）后，平均动脉压（MAP）从127±3降至平均最低值107±4mmHg（P＜0.01），血浆肾素活性（PRA）从20.6±4.8降至10.9±1.7ng/ml/3小时（P＜0.05）。静脉注射卡比多巴（20mg/kg）阻断外周多巴脱羧酶可显著减弱静脉注射α-甲基多巴的降压作用，但MAP仍从145±6降至130±5mmHg（P＜0.001）。静脉注射卡比多巴完全消除了静脉注射α-甲基多巴引起的PRA下降（从16.8±2.8降至16.9±2.1ng/ml/3小时）。脑室内注射卡比多巴（3μg/kg/分钟）未阻断静脉注射α-甲基多巴（0.5mg/kg）的降压作用（从135±8降至113±7mmHg，P＜0.01）或降低肾素的作用（从24.3±5降至13.4±3.2ng/ml/3小时，P＜0.01），但对PRA无影响（从23.4±6降至19.4±7ng/ml/3小时）。脑室内注射α-甲基去甲肾上腺素（2μg/kg）也使MAP从127±5降至112±3mmHg（P＜0.006），但同样未能显著改变PRA（从36.1±11.8降至37.2±15ng/ml/3小时）。这些结果表明，α-甲基多巴在犬中的降压作用既有中枢成分也有外周成分，并且肾素分泌的抑制是由该药物的外周作用引起的。
