title: Endothelial nitric oxide synthase pathophysiology after nonocclusive common carotid artery thrombosis in rats.
abstract: Although vascular dysregulation has been documented in patients with extracranial vascular disease, transient ischemic attacks, and stroke, the pathomechanisms are poorly understood. To model thromboembolic stroke in rats, photochemically induced nonocclusive common carotid artery thrombosis (CCAT) was used to generate a platelet thrombus in the carotid artery of anesthetized rats. After CCAT, platelet aggregates break off the thrombus, travel to the distal cerebral vasculature, damage blood vessels, and cause small infarctions. The authors hypothesized that deficits in the endothelial nitric oxide synthase (eNOS) pathway may be responsible for vascular dysfunction after embolic stroke. To examine the functional status of the eNOS system, they measured eNOS-dependent dilation after CCAT by applying acetylcholine through a cranial window over the middle cerebral artery. The authors also measured eNOS mRNA and protein in the middle cerebral artery to determine whether functional changes were caused by alterations in expression. eNOS-dependent dilation was reduced at 6 hours, elevated at 24 hours, and returned to baseline 72 hours after CCAT. Endothelial nitric oxide synthase mRNA increased at 2 hours and was followed by a rise in protein 24 hours after CCAT. Changes in the eNOS system may account for some of the observed vascular deficits in patients with cerebrovascular disease.
authors.affiliation: Department of Neurological Surgery, University of Miami School of Medicine, Miami, FL 33101, U.S.A.
authors.forename: Gary H
authors.initials: GH
authors.lastname: Danton
authors.forename: Ricardo
authors.initials: R
authors.lastname: Prado
authors.forename: Jessie
authors.initials: J
authors.lastname: Truettner
authors.forename: Brant D
authors.initials: BD
authors.lastname: Watson
authors.forename: W Dalton
authors.initials: WD
authors.lastname: Dietrich
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D002341:Carotid Artery Thrombosis / Q000201:enzymology* / Q000503:physiopathology; D017536:Carotid Artery, Common; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000503:physiopathology; D015870:Gene Expression; D007700:Kinetics; D008297:Male; D020768:Middle Cerebral Artery / Q000187:drug effects / Q000201:enzymology / Q000503:physiopathology; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000502:physiology*; D052250:Nitric Oxide Synthase Type III; D010777:Photochemistry; D010974:Platelet Aggregation; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020521:Stroke / Q000201:enzymology / Q000503:physiopathology; D014664:Vasodilation / Q000187:drug effects
chemical_list: D012333:RNA, Messenger; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D000109:Acetylcholine