Suppression of the cerebral vasospastic actions of oxyhemoglobin by ascorbic acid

Oxyhemoglobin (Oxy-Hb) produced a concentration-dependent contraction of monkey, dog, and bovine cerebral artery strips. Treatment of Oxy-Hb with ascorbic acid suppressed the ability of Oxy-Hb to contract the arteries, especially in the monkey arteries. The ability of intracisternally applied Oxy-Hb to constrict the basilar artery in anesthetized dogs was diminished when Oxy-Hb was treated previously with ascorbic acid (AsA-Hb). The contraction caused by Oxy-Hb was suppressed by treatment with indomethacin and aspirin in isolated bovine cerebral arteries. Endothelium-dependent relaxations elicited by substance P and relaxations induced by stimulation of the vasodilator nerves with nicotine were suppressed by treatment with Oxy-Hb and AsA-Hb; however, the inhibitory effect of AsA-Hb was markedly less. Oxy-Hb attenuated nitroglycerin-induced relaxations in a dose-dependent fashion, whereas AsA-Hb in concentrations up to 1.6 x 10(-5) M did not significantly influence the relaxations. It is concluded that incubation of Oxy-Hb with ascorbic acid alters markedly the biological activity of Oxy-Hb; the vasoconstrictor activity is suppressed, and the ability to diminish vasodilator actions is minimized. These findings provide a rationale for the use of ascorbic acid in cisternal irrigation to prevent the development of cerebral vasospasm after a subarachnoid hemorrhage.