Negative inotropic and chronotropic effects of oxytocin.
We have previously shown that oxytocin receptors are present in the heart and 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 isolated 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+/-9.1% of basal 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 specificity. The effects of oxytocin were also totally inhibited by co-perfusion with 5x10(-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 neurons. Co-perfusion with 10(-6) mol/L NO synthase inhibitor (L-NAME) significantly inhibited oxytocin effects on both beating rate (-1.85+/-1.27% versus -14.7+/-4.9% in oxytocin alone, P<0.05) and force of contraction (-24.9+/-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-NAME at 10(-4) mol/L (-8.1+/-1.8%, P<0.01). These studies imply that the negative inotropic and chronotropic effects of oxytocin are mediated by cardiac oxytocin receptors and that intrinsic cardiac cholinergic neurons and NO are involved in these actions.
Mukaddam-Daher
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Laboratory of Cardiovascular Biochemistry, Centre Hospitalier de L'Université de Montréal Research Center, Pavilion Hotel-Dieu, Montreal, Canada. suhayla.mukaddam-daher@umontreal.ca
Yin
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Roy
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Gutkowska
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Cardinal
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D000818:Animals; D001285:Atropine / Q000494:pharmacology; D046508:Culture Techniques; D003864:Depression, Chemical; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006325:Heart Atria / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects*; D006727:Hormone Antagonists / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010121:Oxytocin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D010276:Parasympatholytics / Q000494:pharmacology
D004791:Enzyme Inhibitors; D006727:Hormone Antagonists; C055830:KB 5-21; D010276:Parasympatholytics; D010121:Oxytocin; D001285:Atropine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester