Garvey H L, Ram N
Eur J Pharmacol. 1975 Sep-Oct;33(2):283-94. doi: 10.1016/0014-2999(75)90172-7.
The mechanism of the antihypertensive effects of propranolol, pindolol and sotalol were investigated using chloralose-anesthetized cats and dogs. When administered i.v. into a carotid or vertebral artery, propranolol was readily taken up by several brain areas. Highest drug concentrations were detected in the hypothalamus and its projection areas and low concentrations in the cerebral cortex and peripheral tissues. Discrete drug administration at several brain sites decreased efferent sympathetic but increased efferent parasympathetic nerve activity. These neural changes were associated with reductions in both blood pressure and heart rate. Hippocampal propranolol administration induced the greatest neural and cardiovascular changes. Significant concurrent reductions in blood pressure, heart rate and cardiac contractile force occurred following propranolol (500 mug) administration into the hippocampus and pindolol (80 mug) administration into the septum. Sotalo injections at various brain sites failed to influence the cardiovascular system. The centrally induced cardiovascular and neural changes induced by both propranolol and pindolol were prevented by pretreatment with hexamethonium. These results suggest that the hypotensive effects of both propranolol and pindolol may be related to a reduction in the level of central autonomic control resulting in decreased levels of blood pressure, heart rate and cardiac contractile force.
使用水合氯醛麻醉的猫和狗研究了普萘洛尔、吲哚洛尔和索他洛尔的降压作用机制。静脉注射到颈动脉或椎动脉时，普萘洛尔很容易被几个脑区摄取。下丘脑及其投射区检测到最高药物浓度，而大脑皮层和外周组织中浓度较低。在几个脑部位进行离散给药可降低传出交感神经活性，但增加传出副交感神经活性。这些神经变化与血压和心率降低有关。海马注射普萘洛尔引起的神经和心血管变化最大。向海马注射普萘洛尔（500微克）和向隔区注射吲哚洛尔（80微克）后，血压、心率和心脏收缩力同时显著降低。在各个脑部位注射索他洛尔未能影响心血管系统。用六甲铵预处理可预防普萘洛尔和吲哚洛尔引起的中枢性心血管和神经变化。这些结果表明，普萘洛尔和吲哚洛尔的降压作用可能与中枢自主控制水平降低有关，从而导致血压、心率和心脏收缩力水平降低。
