Hypoxic Contraction in Isolated Rat Abdominal Aorta: Role of Endothelium and Vascular Smooth Muscle

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Abstract
The effect of severe hypoxia on the vascular tone of isolated rat aortic rings with and without endothelium was studied. Hypoxia induced transient contractions that were significantly more pronounced in preparations with endothelium. These responses were reproducible during two consecutive episodes of hypoxia. With increasing concentrations of phenylephrine (EC 10 to EC 100) the amplitude of endothelium-dependent hypoxic contractions decreased. Indomethacin, the inhibitor of cyclooxygenase, had no effect on hypoxic contractions whereas substances that decrease the cyclic GMP content of vascular smooth muscle cells (methylene blue, nitro-L-arginine) inhibited hypoxic contractions. M&B 22948, a substance that increases the cyclic GMP level, augmented hypoxic contractions. Low concentrations of exogenous donors of nitric oxide (sodium nitroprusside, SIN-1) caused the appearance or significantly augmented hypoxic contractions in preparations without endothelium. This was not observed with the cyclic AMP-dependent vasorelaxant isoproterenol. The measurement of cyclic GMP levels revealed low concentrations in rings without endothelium that increased significantly following stimulation with sodium nitroprusside under control oxygenation. Hypoxia caused a significant transient decrease in cyclic GMP levels. The activity of purified soluble guanylyl cyclase (basal and after stimulation with sodium nitroprusside) increased under hypoxic conditions compared to control oxygenation. These results suggest that hypoxic contraction in rat abdominal aorta is due to a decrease of cyclic GMP content in vascular smooth muscle that is probably not mediated through direct inhibition of guanylyl cyclase.