Activation of alpha 2-adrenoceptors attenuates the inotropic effect of field stimulation in atria.
Guinea-pig left atria were driven to contract at a rate of 0.5 Hz by stimulation with punctate electrodes. For additional field stimulation, a train of one to eight field pulses (30 V; 0.05-0.4 ms duration) was applied during each refractory period. Cholinergic effects were blocked by atropine and thus the resulting increase of the contractile force was caused by noradrenaline released from sympathetic nerve endings. Trains of several short field pulses delivered in the refractory period after each contraction produced a significantly greater inotropic effect than one single pulse of the same total duration delivered in each refractory period. Phentolamine, rauwolscine and idazoxan, by blocking prejunctional alpha 2-adrenoceptors selectively increased the inotropic effect of single field pulses. Selective blockers of alpha 1-adrenoceptors (prazosin, corynanthine) were ineffective in this respect. The effect of alpha 2-adrenoceptor blockers persisted in the presence of noradrenaline uptake blockers (cocaine or desipramine plus corticosterone) or phenylephrine, but was overcome by the alpha 2-adrenoceptor agonists, clonidine and guanabenz. It is concluded that activation of presynaptic alpha 2-adrenoceptors limits the release of noradrenaline by long-lasting single field pulses. Autoinhibition of transmitter release was not seen with trains of short field pulses.
Brasch
H
H
Department of Pharmacology, Medical University of Lübeck, F.R.G.
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D004558:Electric Stimulation; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D012032:Refractory Period, Electrophysiological / Q000187:drug effects
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D011942:Receptors, Adrenergic, alpha; D009638:Norepinephrine