title: Enhancement of the alpha-adrenergic inotropic component of noradrenaline by simultaneous stimulation of muscarinic acetylcholine receptors in rat myocardium.
abstract: The contribution of an alpha-adrenoceptor-mediated component to the final inotropic response to noradrenaline in the absence and presence of muscarinic acetylcholine receptor stimulation (which exerts a 'functional' antagonism of effects mediated through beta-adrenoceptors but not through alpha-adrenoceptors) was evaluated by recording contraction and relaxation in isolated, paced rat papillary muscles. In the absence of muscarinic acetylcholine receptor stimulation, the alpha 1-selective adrenoceptor blocker prazosin (0.12 microM) did not significantly influence the dose-dependent response to noradrenaline with respect to either contractility or to relaxation. In the presence of concomitant muscarinic acetylcholine receptor stimulation by 10 microM carbachol, prazosin reduced by 32% (alpha = 0.028) the maximal increase in contractility (expressed as (dT/dt)max) evoked by noradrenaline compared to the absence of prazosin. Prazosin also did not influence the effect of noradrenaline upon relaxation under these conditions. Carbachol itself did not significantly reduce the maximal contractile response to noradrenaline. Thus cholinergic stimulation increases both relatively and absolutely the alpha-adrenergic inotropic component of noradrenaline. These observations indicate a ternary regulatory system of myocardial contractility through the autonomic receptors.
authors.affiliation: Department of Pharmacology, University of Oslo, Norway.
authors.forename: H B
authors.initials: HB
authors.lastname: Christiansen
authors.forename: G I
authors.initials: GI
authors.lastname: Horgmo
authors.forename: T
authors.initials: T
authors.lastname: Skomedal
authors.forename: J B
authors.initials: JB
authors.lastname: Osnes
mesh_terms: D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D004347:Drug Interactions; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology*; D010210:Papillary Muscles / Q000187:drug effects; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D011950:Receptors, Cholinergic / Q000378:metabolism*; D013997:Time Factors
chemical_list: D011942:Receptors, Adrenergic, alpha; D011950:Receptors, Cholinergic; D002217:Carbachol; D009638:Norepinephrine; D011224:Prazosin