No involvement of nitric oxide in the limitation of beta-adrenergic inotropic responsiveness during ischemia.
We tested whether or not endogenous nitric oxide (NO) attenuates beta-adrenergic inotropic responsiveness during normoperfusion or moderate myocardial ischemia. In 13 anesthetized pigs with a cannulated left anterior descending (LAD) coronary artery, the maximal contractile responses to intracoronary dobutamine and calcium were assessed during normoperfusion and at the end of a 90-min period of moderate ischemia (50% reduction in coronary arterial inflow) without (group 1, n = 6) and with (group 2, n = 7) prior inhibition of NO synthesis [30 mg/kg iv N(omega)-nitro-L-arginine (L-NNA)]. Contractile function was assessed by a regional work index (sonomicrometry, micromanometry, mm. mmHg). In groups 1 and 2 during normoperfusion, the maximal increase of the work index was greater with calcium than with dobutamine. At the end of ischemia in group 1, the baseline work index was decreased by approximately 50%, and the subsequent maximal increase of the work index with dobutamine, but not with calcium, was reduced compared with normoperfusion. In group 2 during normoperfusion, L-NNA did not alter the maximal increases of the work index with dobutamine or calcium. At the end of ischemia, the baseline work index was reduced by 64%, and the subsequent maximal increases of the work index with both dobutamine and calcium were reduced compared with normoperfusion; however, the response to calcium was still greater than that to dobutamine. We conclude that endogenous NO does not limit beta-adrenergic inotropic responsiveness in normoperfused or moderately ischemic porcine myocardium.
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Abeteilung für Pathophysiologie, Zentrum für Innere Medizin des Universitätklinikums Essen, Germany.
Schulz
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Gres
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Heusch
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D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D004280:Dobutamine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006339:Heart Rate / Q000502:physiology; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D017202:Myocardial Ischemia / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D019335:Nitroarginine / Q000494:pharmacology; D010101:Oxygen Consumption / Q000502:physiology; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D013556:Swine, Miniature
D000318:Adrenergic beta-Agonists; D004791:Enzyme Inhibitors; D011943:Receptors, Adrenergic, beta; D019335:Nitroarginine; D009569:Nitric Oxide; D004280:Dobutamine; D002118:Calcium