Influence of the endothelium and alpha-adrenoreceptor antagonists on responses to noradrenaline in the rabbit basilar artery.

Abstract

1. Noradrenaline (10(-6)-10(-2) M) produced slow, concentration-dependent depolarization of smooth muscle cells in the rabbit basilar artery, which preceded the onset of contraction by around 8 s (n = 18). 2. With concentrations greater than 10(-4) M, noradrenaline produced action potentials and fast rhythmic depolarizations superimposed on the slow depolarization. Each fast event was followed by a clear increase in the rate of smooth muscle contraction. The selective alpha 1-adrenoreceptor agonist phenylephrine produced very similar membrane and contractile responses. 3. Action potentials were not produced in artery segments where the endothelium had been removed. In these segments, the amplitude of both contraction and slow depolarization to noradrenaline was similar to that observed in segments with an intact endothelium, but the tension increased more slowly; 84 s compared to the 52 s required to produce 50% of total contraction when the endothelium was functional. 4. The selective alpha 1-antagonist prazosin (10(-6) M) either abolished or significantly reduced both the slow depolarization (with concentrations less than 10(-3) M-noradrenaline) and smooth muscle contraction to noradrenaline. When prazosin was present, action potentials with 10(-3) M-noradrenaline were only produced in 50% of the cells studied. 5. Irreversible blockade of alpha-adrenoreceptors with benextramine (10(-5) M for 20 min) abolished action potentials and both the depolarization and contraction produced with all but the highest concentrations of noradrenaline. With 10(-3) M-noradrenaline, depolarization was produced but it was significantly reduced and usually not associated with smooth muscle contraction. 6. The results show that smooth muscle depolarization, contraction and possibly endothelium-dependent action potentials are produced by alpha-adrenoreceptor stimulation. They also show that noradrenaline-induced action potentials produce smooth muscle contraction, and that slow depolarization is an important, but not absolute requirement for contraction. The fact that action potentials were produced in response to high concentrations of noradrenaline in the presence of prazosin, but not after benextramine, suggests that these concentrations of noradrenaline can surmount competitive antagonism with prazosin.