Changes in the cerebrovascular effects of endothelin-1 and nicardipine after experimental subarachnoid hemorrhage.
The role of endothelium-related factors in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage (SAH) has gained interest since the discovery of endothelin-1 (ET-1). We have examined, before and after SAH, the responsiveness of the cerebrovascular bed of the goat to ET-1, the sources of Ca2+ in ET-1-induced responses, and the ability of the Ca2+ entry blocker nicardipine to counteract them. Before SAH, injection of ET-1 into the cerebral circulation increased cerebrovascular resistance, thereby producing dose-dependent reductions in cerebral blood flow (CBF), which were prevented by nicardipine. In isolated middle cerebral arteries, ET-1 induced concentration-dependent contractions, which were equally inhibited in Ca(2+)-free medium (without or with ethylene glycol tetraacetic acid) and by the Ca2+ entry blocker nicardipine. On the third day after SAH, CBF was reduced by 28% and cerebrovascular resistance increased by 39%. At the same time, both ET-1-induced reductions in CBF and the constricting effects of ET-1 in vitro were enhanced. The ability of nicardipine to increase CBF and to inhibit the effects of ET-1 was impaired as a result of reduced dependence of cerebral arteries on extracellular Ca2+. On the seventh day after SAH, CBF and cerebrovascular resistance returned to control values, and effects of ET-1 became normal. It is suggested that the hyperreactivity to ET-1 of the cerebrovascular bed induced by SAH could have a role in the development of vasospasm, which could reduce the vascular effects of Ca2+ entry blockers after SAH.
Alabadí
J A
JA
Departamento de Fisiología, Universidad de Valencia, Spain.
Salom
J B
JB
Torregrosa
G
G
Miranda
F J
FJ
Jover
T
T
Alborch
E
E
D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000098:blood supply*; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000494:pharmacology*; D005260:Female; D006041:Goats; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects* / Q000502:physiology; D009529:Nicardipine / Q000494:pharmacology*; D013345:Subarachnoid Hemorrhage / Q000503:physiopathology*; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology
D016232:Endothelins; D009529:Nicardipine