Interaction of atrial natriuretic peptide with DA1 receptors in preconstricted isolated perfused rat lungs.
Using an in situ isolated salt-perfused rat lung preparation, we investigated the pulmonary vascular response to atrial natriuretic peptide (ANP). ANP was infused in graded doses ranging from 0.01 to 100.0 micrograms/kg during prostaglandin F2 alpha-induced pulmonary vasoconstriction. These experiments were repeated after selective dopamine1 (DA1) receptor blockade with SCH 23390 and after catecholamine depletion by reserpine. ANP at doses of 0.01, 0.1, 1.0, 10.0, or 100.0 micrograms/kg was injected into the pulmonary artery (n = 5-7/dose). In the unblocked group ANP infusion resulted in a dose-dependent decrease in the mean pulmonary arterial pressure (PAP) with a maximum effect at 10 micrograms/kg (delta PAP = -3.4 +/- 0.2 mm Hg). In the DA1 blockade groups the ANP dose-response curve was shifted to the right, in a parallel fashion. After catecholamine depletion with reserpine, the ANP dose-response curve was identical to that of the unblocked groups. With the parallel, rightward shift of the ANP dose-response curves by SCH 23390 and no attenuation of ANP effect after catecholamine depletion, it appears that ANP vasoactive properties in the pulmonary vasculature involve an interaction with the vascular DA1 receptors. This observation differs from the ANP-dopaminergic interactions seen in the kidney in which ANP action depends on endogenous dopamine transmission.
Polak
M J
MJ
Department of Pediatrics, West Virginia University School of Medicine, Morgantown 26506.
Romano
J T
JT
Taylor
D A
DA
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D001552:Benzazepines / Q000494:pharmacology; D002395:Catecholamines / Q000378:metabolism; D015237:Dinoprost / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D011652:Pulmonary Circulation / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*; D017447:Receptors, Dopamine D1; D012110:Reserpine / Q000494:pharmacology
D001552:Benzazepines; D002395:Catecholamines; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D009320:Atrial Natriuretic Factor; D012110:Reserpine; D015237:Dinoprost