Role of CO and Ca2+‐activated K+ channels in cerebrovascular dilation to glutamate and hypoxia in newborn pigs

Abstract

Large conductance calcium activated K (Kca) channels regulate the physiological functions of many tissues, including cerebrovascular smooth muscle. L-Glutamic acid (glutamate) is the principal excitatory neurotransmitter in the central nervous system and oxygen tension is a dominant local regulator of vascular tone. In the cerebral circulation in vivo, glutamate and hypoxia dilate newborn pig cerebral arterioles and dilations to both are blocked by inhibition of CO production, which occurs via the degradation of heme via heme oxygenase. CO dilates cerebral arterioles by activating Kca channels. The present study was designed to investigate the role of Kca channels in cerebral vasodilation in response to glutamate and hypoxia. Topical application of NS1619, an activator of Kca channels, caused vasodilation that was rapidly reversed by the selective Kca blocker paxillin. In the presence of paxillin, neither CO, glutamate, nor acute hypoxia dilated pial arterioles. Conversely, paxillin did not inhibit dilation to sodium nitroprusside or constriction to hyperoxia. These data suggest that dilations of newborn pig pial arterioles to glutamate and hypoxia are mediated by activation of Kca channels and suggest the intermediary signal is CO.