Role of ATP-sensitive K+ channels in cGMP-mediated pial artery vasodilation.
The present study was designed to investigate the role of ATP-sensitive K+ channels in guanosine 3',5'-cyclic monophosphate (cGMP)-mediated pial artery vasodilation in newborn pigs equipped with a closed cranial window. Sodium nitroprusside (SNP) (10(-8), 10(-6) M), a nitrovasodilator, elicited pial artery dilation that was attenuated by the ATP-sensitive K+ channel antagonist glibenclamide (10(-6) M). On a percentage basis, these responses were 25 +/- 1% for the presence of SNP (10(-6) M) alone, whereas 15 +/- 1% dilation was observed for SNP (10(-6) M) in the presence of glibenclamide (n = 5 pigs). Dilation produced by the cGMP analogue, 8-BrcGMP (10(-8), 10(-6) M), was similarly attenuated by glibenclamide. SNP-induced pial dilation was accompanied by increased cortical periarachnoid cerebrospinal fluid (CSF) cGMP levels, and these biochemical changes were blocked by the soluble guanylate cyclase inhibitor, LY-83583 (10(-5) M). SNP (10(-6) M) alone increased CSF cGMP concentration from 407 +/- 14 to 956 +/- 41 fmol/ml, whereas SNP in the presence of LY-83583 yielded a CSF cGMP concentration of 340 +/- 13, which was no different from the control value of 335 +/- 23 fmol/ml (n = 5 pigs). SNP-induced pial dilation was blunted by LY-83583, whereas 8-BrcGMP-induced dilation was unchanged. Cromakalim (10(-8), 10(-6) M), an ATP-sensitive K+ channel agonist, produced dilation that was blocked by glibenclamide (24 +/- 1 vs. 5 +/- 1% for cromakalim 10(-6) M, in the absence and presence of glibenclamide, respectively, n = 5). These data indicate that activation of ATP-sensitive K+ channels contribute to cGMP-mediated pial artery dilation.
Armstead
W M
WM
Department of Anesthesia, University of Pennsylvania, Philadelphia, USA.
D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D001158:Arteries / Q000187:drug effects / Q000502:physiology; D001769:Blood / Q000378:metabolism; D006152:Cyclic GMP / Q000502:physiology*; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D010841:Pia Mater / Q000098:blood supply*; D015221:Potassium Channels / Q000502:physiology*; D014664:Vasodilation / Q000502:physiology*
D015221:Potassium Channels; D009599:Nitroprusside; D000255:Adenosine Triphosphate; D006152:Cyclic GMP; D005905:Glyburide