Carbon monoxide and cerebral microvascular tone in newborn pigs

The present study addresses the hypothesis that CO produced from endogenous heme oxygenase (HO) can dilate newborn cerebral arterioles. HO-2 protein w as highly expressed in large and small blood vessels, as well as parenchyma , of newborn pig cerebrum. Topically applied CO dose-dependently dilated pi glet pial arterioles in vivo over the range 10(-11)-10(-9) M (maximal respo nse). CO-induced cerebrovascular dilation was abolished by treatment with t he Ca2+-activated K+ channel inhibitors tetraethylammonium chloride and ibe riotoxin. The HO substrate heme-L-lysinate also produced tetraethylammonium -inhibitable, do se-dependent dilation from 5 x 10(-8) to 5 x 10(-7) M (max imal). The HO inhibitor chromium mesoporphyrin blocked dilation of pial art erioles in response to heme-L-lysinate. In addition to inhibiting dilation to heme-L-lysinate, chromium mesoporphyrin also blocked pial arteriolar dil ations in response to hypoxia but did not alter responses to hypercapnia or isoproterenol. We conclude that CO dilates pial arterioles via activation of Ca2+-activated K+ channels and that endogenous HO-2 potentially can prod uce sufficient CO to produce the dilation.