title: Enhanced pial arteriolar sensitivity to bioactive agents following exposure to endothelin-1.
abstract: Effects of prior exposure of pial arterioles to endothelin-1 (ET-1) (10(-9) M) on the constriction induced by the by-products of hemolyzed blood (5-HT, LTC4, LPA, and thromboxane analog U-46619) were examined. Piglets (age: 1-3 d) anesthetized with a mixture of ketamine hydrochloride and acepromazine were implanted with cranial windows, and anesthesia was maintained with alpha-chloralose. Topical applications of the by-products of hemolyzed blood mildly constricted pial arterioles. Following prior exposure of the microvessels to ET-1, application of the by-products of hemolyzed blood produced significantly potentiated and long-lasting constrictions compared to the controls. In another experiment, pretreatment of pial arterioles with U-46619 (10(-8) M) also potentiated the constriction induced by ET-1. The constriction produced was fast and longer-lasting. Thus, these data show that by-products of hemolyzed blood, though not potent vasoconstrictors per se, potently constricted pial arterioles in the presence of ET-1. The same agents in the CSF can also potentiate constriction induced by ET-1. Hence, by-products of hemolyzed blood may play a significant role in the initiation and maintenance of cerebral arterial narrowing observed following intracranial bleeding.
authors.affiliation: Department of Physiology, Cardiovascular Renal Center, The University of Tennessee, Memphis 38163, USA. myakubu@physio1.utmem.edu
authors.forename: M A
authors.initials: MA
authors.lastname: Yakubu
authors.forename: C W
authors.initials: CW
authors.lastname: Leffler
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002536:Cerebral Arteries / Q000187:drug effects* / Q000502:physiology; D019332:Endothelin-1 / Q000494:pharmacology*; D017997:Leukotriene C4 / Q000494:pharmacology; D008246:Lysophospholipids / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D019332:Endothelin-1; D008246:Lysophospholipids; D017997:Leukotriene C4; D012701:Serotonin; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D002118:Calcium