Effects of bilirubin on cerebral arterial tone in vitro.
Hemoglobin and its metabolite, bilirubin, have been shown to be present in high concentrations in CSF following subarachnoid hemorrhage (SAH). Several reports have indicated that hemoglobin is a potent cerebral vasoconstrictor and therefore is considered to be an active principle in the genesis of cerebral vasospasm. The possible role of bilirubin on the genesis of cerebral vasospasm, however, has not been clarified. The effect of bilirubin on cerebral vessel tone was therefore examined using in vitro tissue bath techniques. Bilirubin (10(-5)-3 X 10(-5) M) induced strong constriction of cerebral arteries from the cat, dog, and pig. The vasoconstriction returned to baseline after bilirubin was washed by prewarmed Krebs solution. Vasomotor responses to various vasoactive substances were then examined after bilirubin was washed away (the bilirubin postwash effect). Norepinephrine (NE)-induced but not serotonin- or acetylcholine (ACh)-induced constrictions were significantly potentiated by bilirubin postwash effect. The potentiated NE-induced constriction was attenuated by yohimbine but not by prazosin. This enhanced vasoconstriction was mimicked by clonidine but not by phenylephrine, suggesting that the potentiation of NE-induced constriction by the bilirubin postwash effect was mediated by the alpha 2-adrenoceptor subtype. The bilirubin postwash effect also resulted in blockade of endothelium-dependent vasodilations induced by A-23147, ACh, and ATP without affecting relaxations induced by direct muscle relaxants such as beta-adrenoceptors, papaverine, and sodium nitroprusside. These results indicate that bilirubin induces direct vasoconstriction, potentiates alpha 2-adrenoceptor-mediated vasodilation. These actions of bilirubin may promote an enhanced overall vasoconstriction in vivo. Bilirubin, therefore, may be involved in the genesis of cerebral vasospasm following SAH.
Miao
F J
FJ
Department of Pharmacology, Southern Illinois University School of Medicine, Springfield 62794-9230.
Lee
T J
TJ
D000109:Acetylcholine / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001663:Bilirubin / Q000494:pharmacology*; D002415:Cats; D002536:Cerebral Arteries / Q000187:drug effects*; D004285:Dogs; D004730:Endothelium, Vascular / Q000502:physiology; D005260:Female; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D014666:Vasomotor System / Q000187:drug effects*
D000317:Adrenergic alpha-Antagonists; D012701:Serotonin; D000109:Acetylcholine; D001663:Bilirubin; D009638:Norepinephrine