Interrelation between nitric oxide and endothelin-1 in an experimental acute hypoxia in rats and its intervention.
OBJECTIVE
To study the interrelation between nitric oxide (NO) and endothelin-1 (ET1) in experimental acute hypoxic rats, and to evaluate the mechanism of acute hypoxic pulmonary hypertension affected by NO and ET1 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 ET1 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 ET1 rose up significantly in the acute hypoxic rats, but after L-Arg therapy, it was significantly reduced, however, dexamethasone could not affect plasma ET1. 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 ET1 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.
Wang
Y
Y
Department of Intensive Care Unit, Children's Hospital of Shanghai Medical University, Shanghai 200040, China.
Zhang
L
L
Shen
W
W
Chen
L
L
Fan
S
S
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D019332:Endothelin-1 / Q000097:blood*; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000503:physiopathology*; D000860:Hypoxia / Q000150:complications / Q000503:physiopathology*; D008297:Male; D009569:Nitric Oxide / Q000097:blood*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D051381:Rats
D019332:Endothelin-1; D009569:Nitric Oxide; D003907:Dexamethasone; D001120:Arginine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat