Studies on the mechanism of carbon monoxide-induced coronary vasodilation
Wright, Jackie A
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Dissolved carbon monoxide (CO) produces increased coronary flow, i.e., vasodilation, in isolated rat hearts. It has been suggested that CO may be part of the nitric oxide family of endogenous autacoids and neurotransmitters with physiologic effects. In order to more fully understand the actions of endogenous CO, we investigated the vasodilatory effects of 5% CO dissolved in Krebs-Henseleit buffer on ventricular function in isolated rat hearts and further investigated the mechanism of this vasodilation in porcine coronary artery rings. Dissolved CO (5%-CO 90%-O2 5%CO2) produced 6±2% vasodilation without a significant change in any ventricular function parameters in isolated isovolumic rat hearts. The control group of hearts (95% O2 5%-CO2) vasoconstricted 3±1%. Over the experimental time period only perfusion pressure rose significantly, and the developed pressure and the ±dP/dt (the first derivative of the developed pressure) declined in the control group. The comparison of the ventricular compliance curves revealed no significant differences between either the CO group or the control group compared to a group of hearts perfused with red blood cell-containing perfusate. The best indicators of cardiac work were heart rate and -dP/dt for the control group and heart rate and developed pressure for the CO group. In porcine coronary artery rings, 5% CO (5%-CO 90%-O2 5% CO2) dissolved in Krebs-Henseleit buffer produced a significant transient vasodilation in rings precontracted with 20mM potassium chloride (KCl), but not with 74.7mM KCl. A significant transient vasodilation was also seen at 3 x 10^-6M Prostaglandin F2a(PGF2a), but not at 3 x 10^-5M. In rings equilibrated in calcium-free Krebs-Henseleit buffer precontracted with 3 x 10^-6 M PGF2a, calcium transfer through receptor-operated channels was affected significantly only at 4.0 mM calcium chloride, but not at 0, 0.5, 1.5, 2.5, and 4.0 mM calcium. CO did not significantly affect calcium transfer through voltage-operated calcium channels in rings precontracted with 20 mM KCl. Our results demonstrate that CO does cause transient coronary vasodilation at low but not high doses of KCl and PGF2a but his vasodilation does not involve inhibition of calcium transfer through receptor- or voltage-operated calcium channels. the transient nature of this effect may be related to postulated physiologic effects.