Negative inotropic and chronotropic effects of oxytocin

We have previously shown that oxytocin receptors are present in the heart a nd that perfusion of isolated rat hearts with oxytocin results in decreased cardiac flow rate and bradycardia. The mechanisms involved in the negative inotropic and chronotropic effects of oxytocin were investigated in isolat ed dog right atria in the absence of central mechanisms. Perfusion of atria through the sinus node artery with 10(-6) mol/L oxytocin over 5 minutes (8 mL/min) significantly decreased both beating rate (-14.7 +/-4.9% of basal levels, n=5, P<0.004) and force of contraction (-52.4<plus/minus>9.1% of ba sal levels, n=5, P<0.001). Co-perfusion with 10(-6) mol/L oxytocin receptor antagonist (n=3) completely inhibited the effects of oxytocin on frequency (P<0.04) and force of contraction (P<0.004), indicating receptor specifici ty. The effects of oxytocin were also totally inhibited by co-perfusion wit h 5 X 10(-8) mol/L tetrodotoxin (P<0.02) or 10(-6) mol/L atropine (P<0.03) but not by 10(-6) mol/L hexamethonium, which implies that these effects are neurally mediated, primarily by intrinsic parasympathetic postganglionic n eurons. Co-perfusion with 10(-6) mol/L NO synthase inhibitor (L-NAME) signi ficantly inhibited oxytocin effects on both beating rate (-1.85<plus/minus> 1.27% versus -14.7 +/-4.9% in oxytocin alone, P<0.05) and force of contract ion (-24.9<plus/minus>4.4% versus -52.4 +/-9.1% in oxytocin alone, n=4, P<0 .04). The effect of oxytocin on contractility was further inhibited by L-NA ME at 10(-4) mol/L (-8.1<plus/minus>1.8%, P<0.01). These studies imply that the negative inotropic and chronotropic effects of oxytocin are mediated b y cardiac oxytocin receptors and that intrinsic cardiac cholinergic neurons and NO are involved in these actions.