Prolonged exposure to oxyhemoglobin modifies the response of isolated dog middle cerebral arteries to vasoactive substances.
We exposed helical strips of dog middle cerebral arteries to oxyhemoglobin for 5 hours, rinsed them with bathing medium, and stored them overnight; we compared the responses of strips thus treated with the responses of strips without oxyhemoglobin treatment. Relaxation induced by nicotine was abolished by hexamethonium and was markedly inhibited after exposure to oxyhemoglobin. A low concentration of KCl (5 mM) elicited relaxation that was abolished by ouabain and significantly reduced by oxyhemoglobin. Endothelium-dependent relaxation caused by calcium ionophore A23187 was attenuated, and that caused by substance P was reversed to contraction after exposure to oxyhemoglobin. Contraction elicited by substance P also depended on endothelium and was abolished by indomethacin. Relaxation induced by TRK-100, a stable analogue of prostaglandin I2, was moderately attenuated by oxyhemoglobin. On the other hand, concentration-dependent relaxation induced by papaverine and contractile responses to KCl, serotonin, and prostaglandin F2 alpha were not affected by oxyhemoglobin. Our results indicate that vasodilations mediated by vasodilator nerves, the electrogenic sodium pump, endothelium-derived relaxing factor, and prostaglandin I2 were impaired in dog cerebral arteries exposed to oxyhemoglobin. After exposure to oxyhemoglobin, vascular endothelium appears to participate in cerebroarterial contraction via a release of vasoconstrictor prostaglandins. These actions of oxyhemoglobin may be involved in the genesis of cerebral vasospasm after subarachnoid hemorrhage.
Onoue
H
H
Department of Pharmacology, Shiga University of Medical Sciences, Seta, Japan.
Nakamura
N
N
Toda
N
N
D000818:Animals; D002536:Cerebral Arteries / Q000187:drug effects*; D015237:Dinoprost / Q000494:pharmacology; D004285:Dogs; D005260:Female; D008297:Male; D010108:Oxyhemoglobins / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D013373:Substance P / Q000494:pharmacology; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*
D010108:Oxyhemoglobins; D013373:Substance P; D011189:Potassium Chloride; D015237:Dinoprost