Affiliation:
1. Department of Pharmacology (S.C., J.Z., C.G.S.) and Department of Anatomy and Cell Biology (C.R.A.), The University of Melbourne, Parkville, Victoria, Australia; and Departments of Internal Medicine and Pharmacology, Cardiovascular Center, University of Iowa College of Medicine (Y.C., F.M.F.), Iowa City.
Abstract
Potassium ion (K
+
) normally causes cerebral vasodilatation by activating inwardly rectifying K
+
(K
IR
) channels. We tested whether chronic hypertension affects the magnitude and/or mechanism of K
+
-induced cerebral vasodilatation in vivo. Basilar artery responses were examined in anesthetized Wistar-Kyoto (WKY; mean arterial pressure, 114±4 mm Hg) and spontaneously hypertensive (SHR; 176±3 mm Hg) rats. In WKY, elevating cerebrospinal fluid K
+
concentration from 3 mmol/L to 5 and 10 mmol/L caused vasodilatation (percent maximum, 12±1 and 48±7, respectively). The response to 5 mmol/L K
+
was greater in SHR (percent maximum, 17±2 [
P
<0.05 versus WKY] and 49±4). The K
IR
channel inhibitor, barium ion (Ba
2+
, 100 μmol/L) selectively inhibited dilator responses to 5 and 10 mmol/L K
+
by ≈75% in WKY. In SHR, Ba
2+
had no effect on the response to 5 mmol/L K
+
, and only partially inhibited (by ≈40%) the response to 10 mmol/L K
+
. The nonselective NO synthase (NOS) inhibitor Nω-nitro-
l
-arginine methyl ester, the neuronal NOS (nNOS) inhibitor 1-(2-trifluromethyl-phenyl)imidazole, and the
N
-type calcium channel inhibitor ω-conotoxin GVIA, were all without effect in WKY, but markedly inhibited the response to 5 mmol/L K
+
in SHR. When applied together with Ba
2+
, each of these inhibitors also profoundly reduced responses to 10 mmol/L K
+
in SHR. Immunostaining of basilar arteries revealed that the perivascular nNOS-containing nerve plexus was denser in SHR. Thus, K
+
dilates the normotensive basilar artery predominantly via K
IR
channel activation. During chronic hypertension, small physiological elevations in K
+
dilate the basilar artery by an nNOS-dependent mechanism that appears to be upregulated in a compensatory manner.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Cited by
20 articles.
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