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.
Tognarini
D P
DP
Department of Medicine, University of Melbourne, Royal Melbourne Hospital, Parkville, Australia.
Moulds
R F
RF
D058646:Adrenergic alpha-1 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects*; D002118:Calcium / Q000502:physiology*; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D004146:Dioxanes / Q000494:pharmacology; D005260:Female; D005456:Fluorescent Dyes; D016257:Fura-2; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D058646:Adrenergic alpha-1 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D005456:Fluorescent Dyes; C051731:chlorethylclonidine; C010654:(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane; D003000:Clonidine; D002118:Calcium; D016257:Fura-2; D009638:Norepinephrine