Atrial natriuretic peptide in acute hypoxia-induced pulmonary hypertension in rats.
To test the hypothesis that exogenous atrial natriuretic peptide (ANP) prevents the acute pulmonary pressor response to hypoxia, ANP (20-micrograms/kg bolus followed by 1-microgram.kg-1.min-1 infusion) or vehicle was administered intravenously to conscious rats beginning 3 min before exposure to hypoxia or room air for 90 min. Exogenous ANP abolished the acute pulmonary pressor response to hypoxia in association with marked and parallel increases in plasma ANP and guanosine 5'-cyclic monophosphate (cGMP) and with a significant increase in lung cGMP content. To examine whether endogenous ANP modulates the acute pulmonary pressor response to hypoxia, rats were pretreated with a monoclonal antibody (Ab) to ANP and exposed to hypoxia. Mean pulmonary arterial pressure (MPAP) in the Ab-treated rats was not different from control over the first 6 h of hypoxic exposure. Thereafter, the Ab-treated group had significantly higher MPAP than control. Our data suggest that 1) exogenous ANP blocks the pulmonary pressor response to acute hypoxia via stimulation of cGMP accumulation in the pulmonary vasculature, and 2) endogenous ANP may modulate the subacute, but not acute, phase of hypoxic pulmonary hypertension.
Jin
H
H
Department of Medicine, University of Alabama, Birmingham 35294.
Yang
R H
RH
Chen
Y F
YF
Jackson
R M
RM
Itoh
H
H
Mukoyama
M
M
Nakao
K
K
Imura
H
H
Oparil
S
S
D000208:Acute Disease; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D009320:Atrial Natriuretic Factor / Q000097:blood / Q000276:immunology / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D006152:Cyclic GMP / Q000097:blood / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000517:prevention & control*; D000860:Hypoxia / Q000150:complications*; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D011651:Pulmonary Artery / Q000502:physiology; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains
D000911:Antibodies, Monoclonal; D009320:Atrial Natriuretic Factor; D006152:Cyclic GMP