title: Subarachnoid hemorrhage impairs cerebral blood flow response to nitric oxide but not to cyclic GMP in large cerebral arteries.
abstract: Nitric oxide (NO) increases 3',5'-cyclic guanosine monophosphate (cGMP) in vascular smooth muscle and increases cerebral blood flow (CBF). In early stages of cerebral ischemia, NO plays a beneficial role in sustaining CBF. Subarachnoid hemorrhage (SAH), one of the main causes of ischemia, may impair vascular reactivity to NO. To test the hypothesis, 48 h after SAH was induced in rats, we examined the CBF response to the NO donor, SIN-1 (3-morpholinosydnonimine). We measured CBF by laser-Doppler flowmetry in association with: (1) intracarotid injection (for 30 min) of SIN-1 (1.5 mg/kg), 8-bromo-cGMP (7.5 mg/kg), papaverin (1.5 mg/kg) or vehicle; (2) cortical superfusion (for 90 min) of SIN-1 (10(-5) M) or vehicle through the cranial window. Hypotension produced by these vasodilators was controlled with phenylephrine. Vehicle alone did not change CBF throughout the measurement. Intracarotid infusion of SIN-1 (n = 6/group) increased CBF up to 128.6 +/- 3.9% and 111.9 +/- 2.9% in the control group and the SAH group, respectively. SAH significantly attenuated the response (P < 0.05, ANOVA). SAH did not affect the CBF increases elicited by intracarotid administration of cGMP or papaverin, or cortical superfusion of SIN-1. We conclude that during chronic vasospasm SAH disturbs the pathway between NO release and cGMP production in large cerebral arteries. The impairment accounts for the fragility of the brain in the face of ischemia following SAH.
authors.affiliation: Department of Neurosurgery, Hamamatsu University School of Medicine, Handa-cho, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Yamamoto
authors.forename: S
authors.initials: S
authors.lastname: Nishizawa
authors.forename: T
authors.initials: T
authors.lastname: Yokoyama
authors.forename: H
authors.initials: H
authors.lastname: Ryu
authors.forename: K
authors.initials: K
authors.lastname: Uemura
mesh_terms: D000818:Animals; D001921:Brain / Q000098:blood supply*; D002536:Cerebral Arteries / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D002540:Cerebral Cortex / Q000098:blood supply; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D006152:Cyclic GMP / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000502:physiology*; D007270:Injections, Intra-Articular; D008297:Male; D008981:Molsidomine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D009569:Nitric Oxide / Q000494:pharmacology*; D010208:Papaverine / Q000008:administration & dosage / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D013345:Subarachnoid Hemorrhage / Q000503:physiopathology*; D013997:Time Factors; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D014665:Vasodilator Agents; D010656:Phenylephrine; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; C002385:linsidomine; D008981:Molsidomine; D010208:Papaverine; D006152:Cyclic GMP