Effects of nifedipine on potassium-induced contraction and noradrenaline release in cerebral and extracranial arteries from rabbit.

The present study was designed to evaluate the effects of the calcium antagonist nifedipine on potassium-evoked contractions and release of noradrenaline from sympathetic nerves in rabbit basilar and facial arteries. Contractions were measured isometrically in a small volume organ bath. While noradrenaline (NA) produced strong contractions in facial arteries, the majority of the basilar arteries responded only to the highest concentrations of NA employed (greater than 10 microM) with weak contraction. Prazosin (1 microM) and phentolamine (1-10 microM) effectively antagonized the responses to NA in both types of vessel. In contrast, contractions evoked by potassium (K+, 124 mM) were only slightly reduced by the alpha-adrenoceptor blocking agents, indicating that the participation of endogenous NA in maintaining the contractile response to K+ is either small or negligible in the vessel types studied. Nifedipine concentration-dependently inhibited K+-induced contractions in basilar and facial arteries, the former being significantly more affected as evidenced by the maximum inhibitions (approximately 80% compared to approximately 60%) and IC50 values (approximately 10 nM vs. approximately 30 nM). A combination of nifedipine (0.3 microM) and prazosin (1 microM) or phentolamine (1 microM) further suppressed the K+-evoked contractile response in facial arteries, but failed to do so in basilar arteries, when compared with the effect of nifedipine alone. The depressant effect of the alpha-adrenoceptor blockers was, however, still obtainable after reserpine treatment of the facial artery in vitro. Fluorescence histochemical demonstration of noradrenaline revealed a dense network of adrenergic nerve fibres in the walls of the basilar and facial artery. The vessels were also shown to accumulate 3H-NA and release it upon depolarization with K+. The uptake and subsequent release of 3H-NA were significantly reduced by desipramine (10 microM). Nifedipine (0.3-3.0 microM) failed to alter the K+-evoked 3H-NA efflux from sympathetic nerves in neither of the two vessel types. It may be concluded that nifedipine effectively inhibits K+-evoked contractions in isolated basilar and facial arteries from rabbit without interfering with nerve-mediated NA release. Possible explanations for this selective effect of nifedipine on muscle contraction are discussed.