title: Responses of cerebral arterioles to adenosine 5'-diphosphate, serotonin, and the thromboxane analogue U-46619 during chronic hypertension.
abstract: The goal of this study was to determine whether responses of cerebral arterioles to products released by platelets are impaired in stroke-prone spontaneously hypertensive rats (SHRSP). The diameter of pial arterioles was measured during suffusion with adenosine 5'-diphosphate (ADP), serotonin, and the thromboxane analogue U-46619, using intravital microscopy in normotensive Wistar-Kyoto rats (WKY) and SHRSP (7-10 months old). Responses of cerebral arterioles to ADP and serotonin were profoundly impaired in SHRSP. ADP (10(-5) M) increased pial arteriolar diameter 17 +/- 3% (mean +/- SE) in WKY and only 4 +/- 1% in SHRSP. Serotonin (10(-5) M) increased pial arteriolar diameter 15 +/- 2% in WKY and, in contrast, reduced the diameter 13 +/- 1% in SHRSP. Nitroglycerin produced a similar dilatation of cerebral arterioles in WKY and SHRSP, suggesting that impairment of dilatation in SHRSP in response to ADP and serotonin was not related to nonspecific impairment of vasodilatation in SHRSP. The thromboxane analogue U-46619 produced a similar constriction of arterioles in WKY and SHRSP. We also examined the possibility that impaired dilator responses of cerebral arterioles in SHRSP in response to ADP and serotonin may be related to production of a cyclooxygenase vasoconstrictor substance. Indomethacin (10 mg/kg i.v.) partially restored dilator responses to ADP and serotonin in SHRSP, without altering responses in WKY. Thus, we speculate that vasoactive substances released by platelets may release a prostanoid constrictor substance from cerebral vessels of SHRSP and thereby predispose SHRSP to cerebral ischemia and, perhaps, stroke.
authors.affiliation: Department of Internal Medicine, Veterans Administration Medical Center, Iowa City, Iowa.
authors.forename: W G
authors.initials: WG
authors.lastname: Mayhan
authors.forename: F M
authors.initials: FM
authors.lastname: Faraci
authors.forename: D D
authors.initials: DD
authors.lastname: Heistad
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000244:Adenosine Diphosphate / Q000494:pharmacology*; D000818:Animals; D001160:Arterioles / Q000187:drug effects; D001921:Brain / Q000098:blood supply*; D002908:Chronic Disease; D006973:Hypertension / Q000503:physiopathology*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012701:Serotonin / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects
chemical_list: D011450:Prostaglandin Endoperoxides, Synthetic; D012701:Serotonin; D000244:Adenosine Diphosphate; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D007213:Indomethacin