The effects of nifedipine on alpha 2-adrenoceptor-mediated contractions in several isolated blood vessels from the rabbit.

1. The effects of the dihydropyridine calcium channel blocker, nifedipine, on noradrenaline-induced contractile responses have been examined in several isolated blood vessels from the rabbit, with particular emphasis on responses mediated via postjunctional alpha 2-adrenoceptors. 2. In the isolated renal vein, ear vein, distal saphenous artery, saphenous vein and plantaris vein, 0.1 microM and 1 microM nifedipine reduced responses elicited by 54 mM KCl by more than 70%. The remaining responses were abolished by alpha-adrenoceptor blockade, suggesting the involvement of noradrenaline released from neurones activating a dihydropyridine-resistant mechanism. 3. In the renal vein (alpha 1-), ear vein (predominantly alpha 2-), distal saphenous artery (alpha 1- greater than alpha 2-), saphenous vein and plantaris vein (alpha 2- greater than alpha 1-), 0.01 microM and 0.1 microM nifedipine produced concentration-related reductions in the maximum response to noradrenaline. However, 1 microM nifedipine was no more effective than 0.1 microM nifedipine and the reduction in the maximum varied from 10-25% of the control response. Thus, a sizeable component of the alpha-adrenoceptor-mediated response in all blood vessels is resistant to dihydropyridine calcium channel blockers and this appears to be unrelated to the alpha-adrenoceptor subtype involved. 4. Following irreversible inactivation of alpha 1-adrenoceptors and isolation of functional alpha 2-adrenoceptors in the saphenous vein, plantaris vein and distal saphenous artery (the latter requiring the presence of angiotensin II), the effect of nifedipine on responses to noradrenaline was increased. However, a component of the alpha 2-adrenoceptor response in each preparation was present even after the concentration of nifedipine was increased to 1 microM.(ABSTRACT TRUNCATED AT 250 WORDS)