Carbon monoxide is a major contributor to the regulation of vascular tone in aortas expressing high levels of haeme oxygenase‐1

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Abstract
1 The contribution of haeme oxygenase‐derived carbon monoxide (CO) to the regulation of vascular tone in thoracic aorta was investigated following induction of the inducible isoform of haeme oxygenase (HO‐1). 2 Isometric smooth muscle contractions were recorded in isolated rat aortic ring preparations. Rings were incubated in the presence of the nitric oxide (NO) donor S‐nitroso‐N‐acetyl penicillamine (SNAP, 500 μm) for 1 h, then repetitively washed and maintained for a further 4 h prior to producing a concentration‐response curve to phenylephrine (PE, 1–3000 nm). 3 Treatment with SNAP resulted in increased mRNA and protein expression of aortic HO‐1 and was associated with a significant suppression of the contractile response to PE (P14CO release compared to control, as measured by scintillation counting after incubation of aortas with [2‐14C]‐L‐glycine, the precursor of haeme. Guanosine 3′,5′‐monophosphate (cyclic GMP) content was also greatly enhanced in aortas expressing high levels of HO‐1. 5 Incubation of aortic rings with the NO synthase inhibitor, NG‐monomethyl‐L‐arginine (100 μm), significantly (PBritish Journal of Pharmacology (1998) 125, 1437–1444; doi:10.1038/sj.bjp.0702212