AJP - Heart and Circulatory Physiology, Vol 253, Issue 6 1435-H1440, Copyright © 1987 by American Physiological Society
Impairment of endothelium-dependent responses of cerebral arterioles in chronic hypertension
W. G. Mayhan, F. M. Faraci and D. D. Heistad
Department of Internal Medicine, Veterans Administration Medical Center, Iowa City, Iowa.
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 less than 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 less than 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 arterioles 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.
