Reid I A, MacDonald D M, Pachnis B, Ganong W F
J Pharmacol Exp Ther. 1975 Mar;192(3):713-21.
Two series of experiments were performed in anesthetized dogs to test the hypothesis that the suppression of renin secretion by clonidine results from a centrally mediated decrease in the activity in the renal sympathetic nerves. In the first series, clonidine (1 mug/kg) was administered directly into the third ventricle of a group of dogs in which renal perfusion pressure was controlled by adjusting an aortic clamp. In these animals, clonidine produced hypotension and bradycardia and suppressed plasma renin activity to 39 percent of the control value. These changes in blood pressure and plasma renin activity were closely correlated. Intraventricular clonidine produced similar alterations in blood pressure and heart rate in another group of dogs in which renal perfusion pressure was not controlled, but failed to suppress plasma renin activity. In the second series of experiments, clonidine was administered intravenously in a dose of 30 mug/kg. Intravenous clonidine produced a transient hypertension followed by hypotension, decreased heart rate and suppressed plasma renin activity to 49 percent of the control value. Renal denervation reduced renin secretion and prevented the suppression of renin secretion produced by intravenous clonidine. Thus, these data are consistent with the hypothesis that the suppression of renin secretion by clonidine results from a centrally mediated decrease in renal sympathetic neural tone. This suppression may be overcome by large falls in renal perfusion pressure.
在麻醉犬身上进行了两组实验，以检验可乐定抑制肾素分泌是由中枢介导的肾交感神经活动降低所致这一假说。在第一组实验中，将可乐定（1微克/千克）直接注入一组通过调节主动脉夹来控制肾灌注压的犬的第三脑室。在这些动物中，可乐定导致低血压和心动过缓，并将血浆肾素活性抑制至对照值的39%。血压和血浆肾素活性的这些变化密切相关。在另一组未控制肾灌注压的犬中，脑室内注射可乐定产生了类似的血压和心率变化，但未能抑制血浆肾素活性。在第二组实验中，静脉注射剂量为30微克/千克的可乐定。静脉注射可乐定产生短暂的高血压，随后是低血压、心率减慢，并将血浆肾素活性抑制至对照值的49%。肾去神经支配减少了肾素分泌，并阻止了静脉注射可乐定所产生的肾素分泌抑制。因此，这些数据与可乐定抑制肾素分泌是由中枢介导的肾交感神经张力降低所致这一假说一致。这种抑制可能会被肾灌注压的大幅下降所克服。
