Impairment of endothelium-dependent responses of cerebral arterioles in chronic hypertension

William Mayhan, F. M. Faraci, D. D. Heistad

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Abstract

The goal of this study was to determine whether endothelium-dependent responses are impaired in the cerebral microcirculation of stroke-prone spontaneously hypertensive rats (SHRSP). We measured diameters of cerebral arterioles using intravital microscopy in normotensive rats (WKY) and SHRSP (6-8 mo old). Cerebral vasodilator responses to superfusion with adenosine, which is an endothelium-independent agonist, were similar in WKY and SHRSP. In contrast, cerebral vasodilator responses to superfusion with endothelium-dependent agonists were profoundly impaired in SHRSP. Acetylcholine (10-4 M) increased pial arteriolar diameter 23 ± 2% (means ± SE) in WKY and did not change arteriolar diameter in SHRSP (-2 ± 3%, P < 0.05 vs. WKY). Serotonin (10-5 M) increased pial arteriolar diameter 23 ± 1% in WKY and, in contrast, reduced diameter 11 ± 1% in SHRSP (P < 0.05 vs. WKY). Nitroglycerin and acetylcholine produce vasodilatation by activation of guanosine 3',5'-cyclic monophosphate (cGMP). Nitroglycerin was used to determine whether impaired responses of cerebral arterioles in SHRSP were related to altered cGMP activity. We found similar dilatation of cerebral arterioels in WKY and SHRSP in response to nitroglycerin. Thus impaired endothelium-dependent dilatation in SHRSP is not related to alteration of cGMP activity. We speculate that impairment of cerebral vasodilator responses to endothelium-dependent agonists, including vasoactive substances released by platelets, may predispose SHRSP to cerebral ischemia.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume253
Issue number6
StatePublished - Dec 1 1987

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Arterioles
Endothelium
Hypertension
Nitroglycerin
Vasodilator Agents
Acetylcholine
Dilatation
Inbred WKY Rats
Cyclic GMP
Vasoconstrictor Agents
Inbred SHR Rats
Microcirculation
Brain Ischemia
Vasodilation
Adenosine
Serotonin
Blood Platelets
Stroke

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Impairment of endothelium-dependent responses of cerebral arterioles in chronic hypertension. / Mayhan, William; Faraci, F. M.; Heistad, D. D.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 253, No. 6, 01.12.1987.

Research output: Contribution to journalArticle

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