AHEART May 45/5

Leffler, Charles W., Alberto Nasjletti, Changhua Yu, Robert A. Johnson, Alexander L. Fedinec, and Nicole Walker. Carbon monoxide and cerebral microvascular tone in newborn pigs. Am. J. Physiol. 276 (Heart Circ. Physiol. 45): H1641–H1646, 1999.—The present study addresses the hypothesis that CO produced from endogenous heme oxygenase (HO) can dilate newborn cerebral arterioles. HO-2 protein was highly expressed in large and small blood vessels, as well as parenchyma, of newborn pig cerebrum. Topically applied CO dose-dependently dilated piglet pial arterioles in vivo over the range 10211—1029 M (maximal response). CO-induced cerebrovascular dilation was abolished by treatment with the Ca21-activated K1 channel inhibitors tetraethylammonium chloride and iberiotoxin. The HO substrate heme-L-lysinate also produced tetraethylammonium-inhibitable, dose-dependent dilation from 5 3 1028 to 5 3 1027 M (maximal). The HO inhibitor chromium mesoporphyrin blocked dilation of pial arterioles in response to heme-L-lysinate. In addition to inhibiting dilation to heme-L-lysinate, chromium mesoporphyrin also blocked pial arteriolar dilations in response to hypoxia but did not alter responses to hypercapnia or isoproterenol. We conclude that CO dilates pial arterioles via activation of Ca21-activated K1 channels and that endogenous HO-2 potentially can produce sufficient CO to produce the dilation.