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

1 The local cardiac actions of substance P were examined in isolated p erfused 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 s timulation and hemicholinium-3 perfusion, significantly attenuated the negative inotropic and chronotropic effects of substance P. alpha- an d beta-adrenoceptor blockade by nadolol and phentolamine (10(-6 M) eac h) did not prevent the negative inotropic and chronotropic effects of substance P. This indicates that cholinergic neurones, but not adrener gic neurones, partially mediate the effects of substance P. 4 There wa s no significant difference in the effects of substance P observed bet ween groups with acetylcholine depletion and with cholinoceptor blocka de. This suggests that substance P elicits its effects mainly through release of acetylcholine. 5 These results indicate that substance P ha s 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.