Atrial natriuretic peptide-induced relaxation of pre-constricted isolated rat perfused lungs: a comparison in control and hypoxia-adapted animals.
1. To further understand the vasodilator actions of atrial natriuretic peptide and its role in hypoxic pulmonary hypertension, we studied the effects of atrial natriuretic peptide in the isolated perfused rat lung during normoxic ventilation and after elevation of pulmonary artery pressure by either hypoxic ventilation or infusion of prostaglandin F2 alpha. Control animals were compared with littermates that had become adapted to a 10% O2 environment for 3 weeks. Atrial natriuretic peptide was compared with atriopeptin I and atriopeptin III in order to study its structure-activity relationship. 2. Five experiments, each involving six control and six chronically hypoxic rats, were performed. During normoxic ventilation, atrial natriuretic peptide (30 ng-3 micrograms) produced a dose-dependent reduction in pulmonary artery pressure in chronically hypoxic rats, but had no action in the control animals. 3. Atrial natriuretic peptide dose-dependently abolished hypoxic pulmonary vasoconstriction to a greater extent in chronically hypoxic rats (EC50 98 ng) than in control rats (EC50 298 ng; P less than 0.001). Bolus atrial natriuretic peptide (100 ng) produced a plasma concentration of 22.6 pmol/l at 1 min, which is within the pathophysiological range. Initial plasma atrial natriuretic peptide levels were 9.4 pmol/l in control animals and 27.4 pmol/l in chronically hypoxic rats. 4. Chronically hypoxic rats were more sensitive to atriopeptin I, atriopeptin III and atrial natriuretic peptide than were the control rats (P less than 0.05). Atrial natriuretic peptide and atriopeptin III were equipotent and were 10 times more potent than atriopeptide I in both groups (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Stewart
A G
AG
Department of Medicine and Pharmacology, University of Sheffield, Royal Hallamshire Hospital, U.K.
Thompson
J S
JS
Rogers
T K
TK
Morice
A H
AH
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D015237:Dinoprost / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D010446:Peptide Fragments; D011651:Pulmonary Artery / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D014664:Vasodilation / Q000187:drug effects
D010446:Peptide Fragments; C062525:atrial natriuretic factor prohormone (103-126); D009320:Atrial Natriuretic Factor; C062522:atrial natriuretic factor prohormone (103-123); D015237:Dinoprost