Involvement of calcium in coronary vasoconstriction due to prolonged hypoxia

In this study we employed a hypoxic rat heart model for investigating the mechanisms of coronary spasm. Perfusion of the isolated heart with hypoxic medium resulted in initial coronary dilatation followed by sustained constriction. Pretreatment of rats with 5 mg/kg reserpine did not alter the rate of the magnitude of constriction during 60 minutes of hypoxic perfusion. The hypoxia-induced vasoconstriction was not affected by the inclusion of either 1 or 10 micrograms/ml phentolamine in the perfusion buffer, but phenoxybenzamine (0.1 and 1 microgram/ml) significantly attenuated the degree of constriction. Since phenoxybenzamine and phentolamine were equally effective in preventing the phenylephrine-induced coronary constriction, it is unlikely that the effect of phenoxybenzamine was due to an alpha-receptor blocking property but instead may be accounted for by its calcium channel blocking action. Two calcium channel blockers, verapamil and D-600 (0.1 and 1 microgram/ml), were also effective. The rate of rise in coronary pressure was substantially reduced by decreasing the concentration of calcium and was increased by elevating the concentration of calcium in the perfusion medium, but the magnitude of hypoxia-induced constriction was not affected. These results are consistent with the suggestion that the coronary constriction seen during hypoxia does not involve adrenergic mechanisms but is dependent upon the availability of calcium.