Intracellular Ca2+ and contractile responses to alpha 1-adrenoceptor subtype activation in rat aortic vascular smooth muscle.

To simultaneously and rapidly measure intracellular Ca2+ concentration ([Ca2+]i) and contraction in vascular smooth muscle, the Ca2+ fluorophore, fura-2/acetoxymethyl ester, was incorporated into an intact sample of rat aorta. Noradrenaline produced a biphasic [Ca2+]i response (phase-1 and phase-2) which was different to the monophasic contractile response. Phase-1 of the [Ca2+]i response was a large, fast, transient increase which usually clearly preceded contraction. Phase-2 of the [Ca2+]i response was slower, peaked between 20-40 s after addition of noradrenaline, and often subsequently declined whilst contraction continued to increase. Contraction followed phase-2 of the [Ca2+]i response to noradrenaline more closely than phase-1. WB 4101 (alpha 1A-adrenoceptor antagonist) produced a major reduction in phase-1 of the [Ca2+]i response to noradrenaline, a lesser reduction of phase-2 of the [Ca2+]i response to noradrenaline and least reduction of contraction. Chlorethylclonidine (alpha 1B-adrenoceptor antagonist) reduced phase-1 and phase-2 of the [Ca2+]i response and contraction to noradrenaline to a similar degree. We conclude that noradrenaline produces a biphasic [Ca2+]i increase and that neither alpha 1-adrenoceptor subtype is specifically linked to phase-1 or phase-2 of the [Ca2+]i response to noradrenaline in the rat aorta. However, selective alpha 1B-adrenoceptor activation shows a higher force/[Ca2+]i relationship in comparison to alpha 1A-adrenoceptor activation.