CONTRIBUTION OF K-CA CHANNEL ACTIVATION TO HYPOXIC CEREBROVASODILATION DOES NOT INVOLVE NO

Although nitric oxide (NO) and calcium sensitive K+ channel (K-ca) act ivation contribute to hypoxic pial artery dilation in the piglet, resp onses to the NO releasers SNP and SNAP are unchanged by the K-ca chann el antagonist iberiotoxin. These data suggest that NO does not elicit dilation via K-ca channel activation. The present study was designed t o determine if dilation by K-ca channel activation is mediated by NO i n 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). NS161 9 dilation also was not associated with increased CSF cGMP and was unc hanged 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). I beriotoxin (10(-7) M) attenuated hypoxic dilation but hypoxia associat ed CSF cGMP release was unchanged (418 +/- 11 and 897 +/- 31 vs. 419 /- 10 and 896 +/- 25 fmol/ml for control and moderate hypoxia before a nd after iberiotoxin). Coadministration of L-NNA with iberiotoxin furt her decremented hypoxic pial dilation and blocked the hypoxia-associat ed 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 su ggest that NO and the K-ca channel act at different sites in their con tributions to hypoxic pial artery dilation. (C) 1998 Elsevier Science B.V. All rights reserved.