Effect of phospholipase C blockade on cerebral vasospasm.
BACKGROUND
Delayed cerebral ischemia due to cerebral vasospasm remains a major cause of morbidity and mortality following subarachnoid hemorrhage. Oxyhemoglobin (OxyHb) and vasoconstrictor prostanoids have been suggested as putative spasmogens. We have previously reported a synergistic vasoconstrictive action between thromboxane A(2) (TXA(2)) and OxyHb. In the present study we examine the effect of neomycin, a phospholipase C inhibitor, on the cerebral vasoconstriction induced by TXA(2) and OxyHb.


METHODS
Using an in vitro tissue bath method, we assess the effect of neomycin in a concentration-dependent manner, on isolated porcine basilar arteries constricted by U-46619 (TXA(2) analogue) and OxyHb.


RESULTS
The functional synergism between TXA(2) and OxyHb, leading to significant cerebral vasoconstriction, is attenuated in a dose-dependent manner by neomycin.


CONCLUSIONS
Blockade of phospholipase C may provide an alternative strategy in the treatment of subarachnoid-hemorrhage-induced cerebral vasospasm.
Jadhav
Vikram D
VD
Department of Pharmacology, Southern Illinois University School of Medicine, Springfield, IL, USA.
Jabre
Anthony
A
Lee
Tony Jer-Fu
TJ
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000009:adverse effects / Q000494:pharmacology; D000818:Animals; D001488:Basilar Artery / Q000187:drug effects* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D009355:Neomycin / Q000494:pharmacology* / Q000627:therapeutic use; D010108:Oxyhemoglobins / Q000009:adverse effects / Q000494:pharmacology; D013345:Subarachnoid Hemorrhage / Q000150:complications; D013552:Swine; D013928:Thromboxane A2 / Q000009:adverse effects / Q000031:analogs & derivatives / Q000494:pharmacology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors* / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000009:adverse effects / Q000494:pharmacology; D020301:Vasospasm, Intracranial / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*
D004791:Enzyme Inhibitors; D010108:Oxyhemoglobins; D014662:Vasoconstrictor Agents; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D010738:Type C Phospholipases; D009355:Neomycin