Background/Aims: Endothelium-dependent dilation of skeletal muscle arterioles is mediated by unknown factors in very young rats. We assessed the possible contribution of carbon monoxide (CO) to this dilation and to dilation in older animals. Methods: The effects of de-endothelialization or various pharmacological inhibitors on responses to CO or endothelium-dependent dilators were studied in gracilis muscle arterioles from rats at 3–4 weeks (‘weanlings’) and 6–7 weeks (‘juveniles’). Results: Exogenous CO constricted, rather than dilated, arterioles from both age groups. This constriction was reduced by endothelial removal or NOS inhibition in juvenile, but not weanling, arterioles. In contrast, this constriction was abolished by K+ channel inhibition in weanling, but not juvenile, arterioles. The heme precursor δ-aminolevulinic acid constricted juvenile arterioles but did not affect weanling arterioles. The heme oxygenase inhibitor chromium (III) mesoporphyrin IX abolished the endothelium-dependent dilation of juvenile arterioles to simvastatin, and reduced ACh- and simvastatin-induced dilations of weanling arterioles. Conclusion: These findings suggest that relatively high concentrations of exogenous CO can cause constriction by inhibiting endothelium-derived NO in juvenile arterioles and inhibiting K+ channels in weanling arterioles. Endogenous CO produced at lower concentrations can contribute to endothelium-dependent dilation in both age groups.

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