Klevans L R, Kovacs J L, Kelly R
J Pharmacol Exp Ther. 1976 Feb;196(2):389-95.
dl-Sotalol, dl-pindolol, d-propranolol and dl-propranolol were evaluated for central hypotensive activity in chloralose-anesthetized vagotomized cats. Blood pressure and average evoked potentials recorded from one postganglionic renal nerve were measured during intraventricular (lateral ventricle) or intravenous (radial vein) infusion of each agent. Potentials were evoked in the sympathetic nerve by single shocks to the sciatic nerve. Three concentrations (1, 3, 5 mM) of each compound were infused consecutively for 20 minutes per concentration. The decrease in blood pressure after intraventricular infusion of 1 mM pindolol, 5 mM d-propranolol and 3 mM dl-propranolol was significantly greater than the decrease after intravenous infusion of the same concentrations of each agent. The decrease in the average evoked potential after intraventricular infusion of the 5 mM concentration was greater than the response after intravenous infusion. Consecutive (1, 3, 5 mM) intraventricular or intravenous infusions of sotalol did not significantly change either parameter. During intraventricular infusion of 3 mM dl-propranolol blood pressures was markedly decreased at a time when the average evoked potential was unchanged; however, parallel changes were observed during infusion of the drug in vagotomized cats in which the carotid sinus baroreceptors were also denervated. The results indicate a) that intraventricular administration of d-propranolol, dl-propranolol and dl-pindolol, but not of dl-sotalol, decreased blood pressure and discharge evoked in the postganglionic renal nerve by an action on central sympathetic structures, and b) that baroreceptor activity during hypotension can overcome the depressant effect of dl-propranolol on potentials evoked reflexly in the renal nerve.
在水合氯醛麻醉、切断迷走神经的猫身上评估了消旋索他洛尔、消旋吲哚洛尔、右旋普萘洛尔和消旋普萘洛尔的中枢性降压活性。在每种药物进行脑室内(侧脑室)或静脉内(桡静脉)输注期间,测量血压以及从一条节后肾神经记录的平均诱发电位。通过对坐骨神经进行单次电击在交感神经中诱发电位。每种化合物的三种浓度(1、3、5 mM)连续输注,每种浓度持续20分钟。脑室内输注1 mM吲哚洛尔、5 mM右旋普萘洛尔和3 mM消旋普萘洛尔后血压的下降显著大于静脉内输注相同浓度每种药物后的下降。脑室内输注5 mM浓度后平均诱发电位的下降大于静脉内输注后的反应。连续(1、3、5 mM)脑室内或静脉内输注索他洛尔未显著改变任何一个参数。在脑室内输注3 mM消旋普萘洛尔期间,血压明显下降,而此时平均诱发电位未改变;然而,在切断迷走神经且颈动脉窦压力感受器也去神经支配的猫身上输注该药物期间观察到了平行变化。结果表明:a)脑室内给予右旋普萘洛尔、消旋普萘洛尔和消旋吲哚洛尔(而非消旋索他洛尔)可通过作用于中枢交感神经结构降低血压并减少节后肾神经诱发的放电;b)低血压期间压力感受器活动可克服消旋普萘洛尔对肾神经反射诱发电位的抑制作用。