Nitric oxide synthase and soluble guanylyl cyclase activation are required for hypoxic endothelium-dependent contractions of the porcine coronary artery

Abstract

The vasoconstrictor response to hypoxia in the lung, termed hypoxic pulmonary vasoconstriction, is also observed in coronary arteries. The present study examined the mechanism underlying hypoxic contractions in isolated porcine coronary arteries. Isometric tension was measured in rings with or without endothelium. In quiescent preparations, the contractile response to hypoxia was only observed in rings with endothelium and was abolished by indomethacin and S18886, demonstrating the involvement of cyclooxygenase products and TP receptor activation, respectively. In contracted preparations, the hypoxic response was also endothelium-dependent and was reduced by indomethacin and S18886. The endothelium-dependent hypoxic contractions were abolished by L-NAME, ODQ and NS2028 in both quiescent and contracted preparations. The addition of DetaNONOate in the presence of L-NAME restored the hypoxic response, suggesting the involvement of the nitric oxide pathway. Assay of the cyclic GMP content showed no change upon exposure to hypoxia in preparations with and without endothelium. The relaxation to 8-Br-cGMP was not reduced during hypoxia, meaning that the hypoxic contraction is not due to abolition of a basal relaxing component. These experiments suggest that hypoxic endothelium-dependent contractions of the porcine coronary artery depend on more than one signaling pathway.