Mouse cerebral arteries dilate to carbon monoxide

Abstract

Carbon monoxide (CO) is produced endogenously by heme oxygenase (HO) and CO is a vasodilator in some vessel beds. The constitutive isoform of HO, HO-2, is normally present in the vasculature, including cerebral vessels. In the cerebral vasculature CO dilates in some species (i.e. piglet) but not in others (i.e. rat). We investigated cerebrovascular function, including responses to CO and to inhibition of HO, in the middle cerebral artery (MCA) of both wild-type (w.t.) and HO-2 deficient (KO) mice. Dilation to UTP (10−4 M) in isolated, pressurized, and perfused MCAs preconstricted with phenlyephrine (PE) was similar in w.t. and KO mice (96±4% vs 96±5% respectively). Interestingly, inhibition of nitric oxide (NO) synthase and cyclooxygenase did not alter dilation to UTP in either genotype. Constriction to PE (10−6 M to 10−4 M) was also virtually identical in both genotypes reaching a maximum of 36±2% in w.t. and 33±3% in KO mice. Dilation to authentic NO (10−10 M to 10−7 M) reached a maximum of 59±9% in w.t. mice at 10−7 M, and was a similar 62±4% in KO mice. CO (10−7 M to 10−4 M) dose-dependently dilated the MCA of both w.t. and KO mice reaching 71±10% and 54±9% respectively. The HO inhibitor, Cr(III) mesoporphyrin IX (10−5 M), did not alter vascular diameter in either genotype. The heme precursor, δ-aminolevulinic (δ-ALA), acid caused dilation of some, but not all w.t. MCAs, whereas no MCA from KO mice dilated to δ-ALA. Thus, exogenous CO is capable of dilating the mouse MCA, however, the endogenous production of CO does not appear to be an important mediator of vascular function in the mouse MCA. This work was supported by F32 HL080916-01 and T32 HL072754.