Selective hemoglobin inhibition of endothelium-dependent vasodilation of rabbit basilar artery

The effect of hemoglobin on endothelium-dependent vasodilation of the isolated rabbit basilar artery was examined using an isometric tension recording method. Acetylcholine (ACh) (10(-7) - (10(-4) M) evoked a dose-dependent vasodilation of isolated rabbit basilar artery previously contracted by 10(-6) M serotonin. This vasodilating action disappeared after removal of the endothelium. The ACh-induced vasodilation of rabbit basilar artery is thought to be strictly endothelium-dependent. Hemoglobin (10(-7) - 10(-5) M) inhibited this ACh-induced endothelium-dependent vasodilation conditional upon the dose. Adenosine triphosphate (ATP, 10(-7) - 10(-4) M) also relaxed isolated rabbit basilar artery already contracted by 10(-6) M serotonin. This vasodilating action was slightly inhibited by adenosine antagonist, 8-phenyltheophylline (8-PT), and markedly attenuated by removal of the endothelium. This ATP-induced vasodilation is thought to be composed of ATP itself (endothelium-dependent) and ATP degradation products (endothelium-independent) such as adenosine monophosphate or adenosine. Hemoglobin markedly inhibited ATP-induced vasodilation, but there still remained a small vasodilation, which was blocked by 8-PT. Papaverine-induced vasodilation was not affected by removal of the endothelium, and hemoglobin did not inhibit the papaverine-induced vasodilation. These results suggest that rabbit basilar artery has endothelium-dependent vasodilating mechanisms induced by ACh and ATP, and that hemoglobin selectively blocks the endothelium-dependent vasodilation. This finding may relate to the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage: there is a possibility that the presence of hemoglobin released from lysed erythrocytes inhibits the endothelium-dependent vasodilation of cerebral arteries; furthermore, the endothelial degeneration following subarachnoid hemorrhage may impair the vasodilating mechanisms of cerebral artery smooth-muscle cells.