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

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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 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.