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(Hypertension. 2002;39:880.)
© 2002 American Heart Association, Inc.

Scientific Contributions

Neuronal NO Mediates Cerebral Vasodilator Responses to K⁺ in Hypertensive Rats

Sophocles Chrissobolis; James Ziogas; Colin R. Anderson; Yi Chu; Frank M. Faraci; Christopher G. Sobey

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.

Correspondence to Christopher G. Sobey, PhD, Department of Pharmacology, The University of Melbourne, Parkville, Victoria 3010, Australia. E-mail cgsobey{at}unimelb.edu.au

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 (Ba²⁺, 100 µmol/L) selectively inhibited dilator responses to 5 and 10 mmol/L K⁺ by 75% in WKY. In SHR, Ba²⁺ 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 N-nitro-L-arginine methyl ester, the neuronal NOS (nNOS) inhibitor 1-(2-trifluromethyl-phenyl)imidazole, and the N-type calcium channel inhibitor -conotoxin GVIA, were all without effect in WKY, but markedly inhibited the response to 5 mmol/L K⁺ in SHR. When applied together with Ba²⁺, 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.

Key Words: cerebral arteries • genetics • nitric oxide • potassium • potassium channels

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