LOCAL CARDIAC EFFECTS OF SUBSTANCE-P - ROLES OF ACETYLCHOLINE AND NORADRENALINE

1 The local cardiac actions of substance P were examined in isolated perfused hearts and atria of the guinea-pig. 2 In both hearts and right atria, substance P caused negative inotropic and chronotropic effects. 3 Atropine (10(-6) M) or depletion of acetylcholine, by electrical stimulation and hemicholinium-3 perfusion, significantly attenuated the negative inotropic and chronotropic effects of substance P. alpha- and beta-adrenoceptor blockade by nadolol and phentolamine (10(-6 M) each) did not prevent the negative inotropic and chronotropic effects of substance P. This indicates that cholinergic neurones, but not adrenergic neurones, partially mediate the effects of substance P. 4 There was no significant difference in the effects of substance P observed between groups with acetylcholine depletion and with cholinoceptor blockade. This suggests that substance P elicits its effects mainly through release of acetylcholine. 5 These results indicate that substance P has negative inotropic and chronotropic effects in guinea-pig hearts and right atria mediated partly by release of acetylcholine. Substance P also appears to have direct effects on cardiac tissue.