Reversal of hypercapnia induces KATP channel and NO-independent constriction of basilar artery in rabbits with acute metabolic alkalosis.

The mechanism of hypocapnic constriction of the cerebral vasculature under conditions of altered acid-base balance has not been investigated. As K(ATP) channels and NO have been implicated in hypocapnic constriction, this study investigated their roles in the constriction due to lowered pCO(2) in hypercapnic rabbits with acute metabolic alkalosis. Metabolic alkalosis was induced acutely following ketamine/xylazine injection. Lowering blood pCO(2) from initial baseline hypercapnic levels to near normocapnic and hypocapnic levels constricted basilar artery by 10.2+/-0.8% (4) and 16.2+/-0.6% (44), respectively (means+/-S.E., n), as determined in an in situ cranial window preparation. The constrictions were maintained for 4-5 h and return of pCO(2) to hypercapnic levels relaxed the constriction. Changing the suffusate pH to either the pH of the cerebral spinal fluid observed during initial baseline hypercapnia or following lowered pCO(2) did not alter the magnitude of constriction due to lowered pCO(2). Neither 0.3 mM N(G)-monomethyl-L-arginine monoacetate, an NO synthase inhibitor, nor 10 microM glibenclamide, a K(ATP) channel blocker, altered the magnitude of hypocapnic constriction. These results demonstrated that under conditions of acute metabolic alkalosis and accompanying compensatory hypercapnia, subsequent pCO(2) reduction induces prolonged constriction of the basilar artery that is independent of (1) cerebral spinal fluid pH over a physiologic range, and (2) NO and K(ATP) channels.