Contribution of alpha-adrenoceptors to depolarization and contraction evoked by continuous asynchronous sympathetic nerve activity in rat tail artery.

1. The effects of continuous but asynchronous nerve activity induced by ciguatoxin (CTX-1) on the membrane potential and contraction of smooth muscle cells have been investigated in rat proximal tail arteries isolated in vitro. These effects have been compared with those produced by the continuous application of phenylephrine (PE). 2. CTX-1 (0.4 nM) and PE (10 microM) produced a maintained depolarization of the arterial smooth muscle that was almost completely blocked by alpha-adrenoceptor blockade. In both cases, the depolarization was more sensitive to the selective alpha-adrenoceptor antagonist, idazoxan (0.1 microM), than to the selective alpha 1-adrenoceptor antagonist, prazosin (0.01 microM). 3. In contrast, the maintained contraction of the tail artery induced by CTX-1 (0.2 nM) and PE (2 and 10 microM) was more sensitive to prazosin (0.01) microM, than to idazoxan (0.01 microM). In combination, these antagonists almost completely inhibited contraction to both agents. 4. Application of the calcium channel antagonist, nifedipine (1 microM), had no effect on the depolarization induced by either CTX-1 or PE but maximally reduced the force of the maintained contraction to both agents by about 50%. 5. We conclude that the constriction of the tail artery induced by CTX-1, which mimics the natural discharge of postganglionic perivascular axons, is due almost entirely to alpha-adrenoceptor activation. The results indicate that neuronally released noradrenaline activates more than one alpha-adrenoceptor subtype. The depolarization is dependent primarily on alpha 2-adrenoceptor activation whereas the contraction is dependent primarily on alpha 1-adrenoceptor activation. The links between alpha-adrenoceptor activation and the voltage-dependent and voltage-independent mechanisms that deliver Ca2+ to the contractile apparatus appear to be complex.