Contribution of Kca channel activation to hypoxic cerebrovasodilation does not involve NO

Although nitric oxide (NO) and calcium sensitive K+ channel (K-ca) activation contribute to hypoxic pial artery dilation in the piglet, responses to the NO releasers SNP and SNAP are unchanged by the K-ca channel antagonist iberiotoxin. These data suggest that NO does not elicit dilation via K-ca channel activation. The present study was designed to determine if dilation by K-ca channel activation is mediated by NO in newborn pigs equipped with a closed cranial window. NS1619 (10(-8), 10(-6) M), a K-ca 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 RD 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 K-ca channel activation is not mediated by NO/cGMP. Further, these data suggest that NO and the K-ca channel act at different sites in their contributions to hypoxic pial artery dilation. (C) 1998 Elsevier Science B.V. All rights reserved.