Neuronal NO mediates cerebral vasodilator responses to K+ in hypertensive rats.
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.
Chrissobolis
Sophocles
S
Department of Pharmacology, The University of Melbourne, Parkville, Victoria, Australia.
Ziogas
James
J
Anderson
Colin R
CR
Chu
Yi
Y
Faraci
Frank M
FM
Sobey
Christopher G
CG
D000818:Animals; D001464:Barium / Q000494:pharmacology; D001488:Basilar Artery / Q000187:drug effects / Q000201:enzymology / Q000503:physiopathology; D002536:Cerebral Arteries / Q000201:enzymology / Q000503:physiopathology*; D002908:Chronic Disease; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006973:Hypertension / Q000201:enzymology / Q000378:metabolism / Q000503:physiopathology*; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000201:enzymology / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000502:physiology*; D052248:Nitric Oxide Synthase Type I; D011188:Potassium / Q000494:pharmacology*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000096:biosynthesis; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors; D014664:Vasodilation / Q000187:drug effects
D004791:Enzyme Inhibitors; D007093:Imidazoles; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D001464:Barium; C098186:1-(2-trifluoromethylphenyl)imidazole; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium; D019331:NG-Nitroarginine Methyl Ester