Global
cerebral ischemia and subsequent reperfusion induce early impairment of the
vasodilator responses to
hypercapnia and vasoactive substances.
Nitric oxide (NO) is involved in the regulation of cerebral blood flow (CBF) in both health and disease. The present study was designed to assess possible changes in the cerebrovascular reactivity to NO donors induced by
cerebral ischemia-reperfusion in goats. Female goats (n = 9) were subjected to 20 min global
cerebral ischemia under
halothane/N2O
anesthesia. Sixteen additional goats were
sham-operated as a control group. One week later the effects of
ischemia-reperfusion on relaxations to NO donors
sodium nitroprusside (SNP),
diethylamine/NO (
DEA/NO),
diethylenetriamine/NO (
DETA/NO), and
spermine/NO (
SPER/NO) were studied in rings of middle cerebral artery (MCA) isolated in an organ bath for isometric tension recording. SNP,
DEA/NO,
DETA/NO, and
SPER/NO induced concentration-dependent relaxations of MCA precontracted with KCl (
DEA/NO >
SPER/NO > SNP >
DETA/NO) or with
endothelin-1 (
DEA/NO > SNP >
SPER/NO >
DETA/NO). Relaxations were always higher in endothelin-1-precontracted arteries. One week after
cerebral ischemia concentration-response curves to SNP and
DEA/NO were displaced to the right, indicating a reduction in relaxant potency of NO donors. The classical nitrovasodilator SNP and NONOates induce relaxation of isolated goat MCA which is partially inhibited by arterial depolarization. Global
cerebral ischemia followed by reperfusion induces delayed impairment of the relaxant effects of NO on cerebrovascular smooth muscle, which results in reduced vasodilatory potency of NO donors in large cerebral arteries.