Interrelation between nitric oxide and endothelin-1 in an experimental acute hypoxia in rats and its intervention

Objectives To study the interrelation between nitric oxide (NO) and endothelin 1 (ET 1) in experimental acute hypoxic rats, and to evaluate the mechanism of acute hypoxic pulmonary hypertension affected by NO and ET 1 and its intervention.Methods Nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase histochemical staining method, Griess biochemical assay and radioimmune assay were applied to investigate the changes of nitric oxide syntheses (NOS), NO and ET 1 in normal, hypoxic, and L Arginine (L Arg) and dexamethasone treated hypoxic rats.Results In normal rats, the NOS stain was localized in pulmonary vascular endothelium, and in the hypoxic rats, the activity of NOS was significantly lower. The level of plasma NO was significantly lower during acute hypoxia, but L Arg as well as dexamethasone could prevent the drop of plasma NO. The level of plasma ET 1 rose up significantly in the acute hypoxic rats, but after L Arg therapy, it was significantly reduced, however, dexamethasone could not affect plasma ET 1. The level of plasma cyclic guanosine monophosphate (cGMP) was significantly lower in the acute hypoxic rats, and L Arg could prevent the drop of plasma cGMP, but dexamethasone could not prevent the drop of plasma cGMP. Conclusions NO and ET 1 may modulate hypoxic pulmonary hypertension and acute hypoxia can result in acute hypoxic pulmonary hypertension. L Arg can reverse the acute hypoxic pulmonary hypertension. Further study is needed if dexamethasone is beneficial in acute hypoxic diseases. NO may play an important role in physiology of the lung and acute hypoxic diseases.