Studies on the mechanism of carbon monoxide-induced vasodilation in the isolated perfused rat heart.
We investigated the effects of dissolved CO on isolated potassium-arrested (K+) perfused rat hearts. Hearts from male Sprague-Dawley rats were perfused via the aorta with oxygenated Krebs-Henseleit solution containing 20 mM K+. Coronary flow (Qt) averaged 48.8 +/- 1.6 (SE), 48.1 +/- 1.7, and 55.6 +/- 1.7 ml/min/g dry wt when the perfusate was equilibrated with 95% O2-5% CO2, 5% N2-90% O2-5% CO2, and 5% CO-90% O2-5% CO2, respectively. The change in Qt was statistically significant when CO was present in the perfusion medium, but was not significant when N2 was present. Furthermore, the effect was reversible because coronary flow returned to control levels when CO was removed. Myocardial oxygen consumption (MVO2) did not change significantly when hearts were perfused with either N2 or CO. The magnitude of CO-induced vasodilation was not affected significantly by the addition of either 5 microM propranolol, 2 microM phentolamine, 1 unit of adenosine deaminase, or 0.1 mM indomethacin to the perfusate. In addition, CO reversed the vasoconstrictive effects of the alpha-agonist methoxamine. These results indicate that CO exerts a vasodilatory effect on coronary vasculature that is not the result of decreased O2 content in the perfusate and is not mediated by adrenergic influences, adenosine, or prostaglandins.
D000243:Adenosine Deaminase / Q000494:pharmacology; D000818:Animals; D002248:Carbon Monoxide / Q000494:pharmacology*; D003331:Coronary Vessels / Q000187:drug effects*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects; D010477:Perfusion; D011453:Prostaglandins / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D011943:Receptors, Adrenergic, beta / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*
D011453:Prostaglandins; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D002248:Carbon Monoxide; D000243:Adenosine Deaminase; D007213:Indomethacin