Kunze D L, Andresen M C, Torres L A
J Pharmacol Exp Ther. 1986 Nov;239(2):303-10.
This study examined the effects of antagonists known to act on voltage-dependent calcium channels (chiefly nitrendipine, diltiazem and verapamil) on arterial baroreceptor function. Single fiber discharge of aortic arch baroreceptor preparations of the rat was not altered at concentrations ranging from 10(-11) to 10(-6) M. Increasing pressure in an isolated perfused carotid sinus in the cat produced a reflex arterial pressure response which was not altered significantly when the carotid perfusate contained an antagonist concentration of 10(-7) to 10(-6) M. A higher concentration (10(-5) M) of all three antagonists decreased baroreceptor discharge and depressed the reflex response. In addition, nimodipine and nifedipine had uniformly similar dose-related effects. It is likely that the effects found at the elevated concentrations are nonspecific and probably are independent of voltage-dependent calcium channels. No differences between the dihydropyridine blockers and verapamil were found even at very high doses. Our results suggest that within the range of doses used clinically these antagonists do not directly affect baroreceptor function. In addition, the present results reinforce the notion that voltage-dependent calcium channels are not importantly involved in baroreceptor transduction as suggested by earlier studies of the effects of changing external calcium concentration.
本研究考察了已知作用于电压依赖性钙通道的拮抗剂(主要是尼群地平、地尔硫䓬和维拉帕米)对动脉压力感受器功能的影响。在10⁻¹¹至10⁻⁶M的浓度范围内,大鼠主动脉弓压力感受器制备物的单纤维放电未发生改变。在猫的离体灌注颈动脉窦中增加压力会产生反射性动脉压反应,当颈动脉灌注液中含有10⁻⁷至10⁻⁶M的拮抗剂浓度时,该反应未发生显著改变。所有三种拮抗剂的较高浓度(10⁻⁵M)均降低了压力感受器放电并抑制了反射反应。此外,尼莫地平和硝苯地平具有一致的相似剂量相关效应。在升高的浓度下发现的效应可能是非特异性的,并且可能与电压依赖性钙通道无关。即使在非常高的剂量下,二氢吡啶阻滞剂和维拉帕米之间也未发现差异。我们的结果表明,在临床使用的剂量范围内,这些拮抗剂不会直接影响压力感受器功能。此外,目前的结果强化了这样一种观念,即如早期关于改变细胞外钙浓度影响的研究所表明的,电压依赖性钙通道在压力感受器转导中并不重要。