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 micromol/L) selectively inhibited dilator responses to 5 and 10 mmol/L K+ by approximately 75% in WKY. In SHR, Ba2+ had no effect on the response to 5 mmol/L K+, and only partially inhibited (by approximately 40%) the response to 10 mmol/L K+. The nonselective NO synthase (NOS) inhibitor N(omega)-nitro-L-arginine methyl ester, the neuronal NOS (nNOS) inhibitor 1-(2-trifluromethyl-phenyl)imidazole, and the N-type calcium channel inhibitor omega-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.