Responses of cerebral arterioles to adenosine 5'-diphosphate, serotonin, and the thromboxane analogue U-46619 during chronic hypertension

W. G. Mayhan, F. M. Faraci, D. D. Heistad

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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 substance released by platelets may release a prostanoid constrictor substance from cerebral vessels of SHRSP and thereby predispose SHRSP to cerebral ischemia and, perhaps, stroke.

Original languageEnglish (US)
Pages (from-to)556-561
Number of pages6
JournalHypertension
Volume12
Issue number6
DOIs
StatePublished - Jan 1 1988

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15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
Inbred WKY Rats
Thromboxanes
Arterioles
Adenosine Diphosphate
Serotonin
Hypertension
Dilatation
Blood Platelets
Stroke
Nitroglycerin
Vasoconstrictor Agents
Inbred SHR Rats
Prostaglandin-Endoperoxide Synthases
Brain Ischemia
Constriction
Vasodilation
Indomethacin
Prostaglandins

ASJC Scopus subject areas

  • Internal Medicine

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Responses of cerebral arterioles to adenosine 5'-diphosphate, serotonin, and the thromboxane analogue U-46619 during chronic hypertension. / Mayhan, W. G.; Faraci, F. M.; Heistad, D. D.

In: Hypertension, Vol. 12, No. 6, 01.01.1988, p. 556-561.

Research output: Contribution to journalArticle

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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 substance released by platelets may release a prostanoid constrictor substance from cerebral vessels of SHRSP and thereby predispose SHRSP to cerebral ischemia and, perhaps, stroke.",
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