title: Relaxant effects of sodium nitroprusside and NONOates in goat middle cerebral artery: delayed impairment by global ischemia-reperfusion.
abstract: 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.
authors.affiliation: Centro de Investigación, Hospital Universitario La Fe, Departamento de Biología Animal, Universidad de Valencia, Spain. jbsalom@san.gva.es
authors.forename: J B
authors.initials: JB
authors.lastname: Salom
authors.forename: M D
authors.initials: MD
authors.lastname: Barberá
authors.forename: J M
authors.initials: JM
authors.lastname: Centeno
authors.forename: M
authors.initials: M
authors.lastname: Ortí
authors.forename: G
authors.initials: G
authors.lastname: Torregrosa
authors.forename: E
authors.initials: E
authors.lastname: Alborch
mesh_terms: D000818:Animals; D002536:Cerebral Arteries / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006041:Goats; D009126:Muscle Relaxation / Q000187:drug effects; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology*; D015427:Reperfusion Injury / Q000503:physiopathology*
chemical_list: D020030:Nitric Oxide Donors; D009599:Nitroprusside