Contribution of kca channel activation to hypoxic cerebrovasodilation does not involve NO.
Although nitric oxide (NO) and calcium sensitive K+ channel (Kca) activation contribute to hypoxic pial artery dilation in the piglet, responses to the NO releasers SNP and SNAP are unchanged by the Kca channel antagonist iberiotoxin. These data suggest that NO does not elicit dilation via Kca channel activation. The present study was designed to determine if dilation by Kca channel activation is mediated by NO in newborn pigs equipped with a closed cranial window. NS1619 (10(-8), 10(-6) M), a Kca agonist, produced dilation that was unchanged by the NO synthase inhibitor, L-NNA (10(-6) or 10(-3) M) (11+/-1 and 20+/-1 vs. 11+/-1 and 18+/-1% before and after L-NNA 10(-3) M). NS1619 dilation also was not associated with increased CSF cGMP and was unchanged by Rp 8-Bromo cGMPs, a cGMP antagonist (9+/-1 and 17+/-1 vs. 9+/-1 and 16+/-2% before and after Rp 8-Bromo cGMPs 10(-5) M). Iberiotoxin (10(-7) M) attenuated hypoxic dilation but hypoxia associated CSF cGMP release was unchanged (418+/-11 and 897+/-31 vs. 419+/-10 and 896+/-25 fmol/ml for control and moderate hypoxia before and after iberiotoxin). Coadministration of L-NNA with iberiotoxin further decremented hypoxic pial dilation and blocked the hypoxia-associated rise in CSF cGMP. These data show that pial artery dilation by Kca channel activation is not mediated by NO/cGMP. Further, these data suggest that NO and the Kca channel act at different sites in their contributions to hypoxic pial artery dilation.
Department of Anesthesia, University of Pennsylvania and The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
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Armstead
D000818:Animals; D001158:Arteries / Q000187:drug effects; D001562:Benzimidazoles / Q000494:pharmacology; D002560:Cerebrovascular Circulation / Q000502:physiology*; D006152:Cyclic GMP / Q000502:physiology; D004723:Endorphins / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D000860:Hypoxia / Q000503:physiopathology*; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D019335:Nitroarginine / Q000494:pharmacology; D010841:Pia Mater / Q000098:blood supply; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000819:agonists / Q000502:physiology*; D024681:Potassium Channels, Calcium-Activated; D013552:Swine; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D001562:Benzimidazoles; D004723:Endorphins; D004791:Enzyme Inhibitors; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; C086491:NS 1619; D019335:Nitroarginine; D009569:Nitric Oxide; D006152:Cyclic GMP