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.
Kawakami
M
M
Department of Pharmacology, Shiga University of Medical Sciences, Ohtsu, Japan.
Kodama
N
N
Toda
N
N
D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology; D001488:Basilar Artery / Q000187:drug effects / Q000502:physiology; D002417:Cattle; D002536:Cerebral Arteries / Q000187:drug effects / Q000502:physiology; D004285:Dogs; D005260:Female; D002546:Ischemic Attack, Transient / Q000503:physiopathology*; D008251:Macaca; D008297:Male; D009538:Nicotine / Q000494:pharmacology; D005996:Nitroglycerin / Q000494:pharmacology; D010108:Oxyhemoglobins / Q000502:physiology*; D011189:Potassium Chloride / Q000494:pharmacology; D013373:Substance P / Q000494:pharmacology; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects
D010108:Oxyhemoglobins; D013373:Substance P; D011189:Potassium Chloride; D009538:Nicotine; D005996:Nitroglycerin; D001205:Ascorbic Acid; D001241:Aspirin