title: Atrial natriuretic peptide clearance receptor agonist lowers pulmonary pressure in hypoxic rats.
abstract: We demonstrated previously that intravenous administration of exogenous atrial natriuretic peptide (ANP) lowers mean pulmonary arterial pressure (MPAP) in hypoxia-adapted rats. To test the hypothesis that endogenous ANP may also lower MPAP in this model, C-ANP-(4-23), a ring-deleted analogue of ANP that binds to the biologically silent ANP clearance receptor (C-ANP receptor) but not to the ANP biological receptor (B-ANP receptor), was administered intravenously as a bolus injection (10 micrograms/kg) followed by an infusion (1 micrograms.kg-1.min-1 for 60 min) to rats adapted to hypoxia (10% O2) for 4 wk and to air control rats. C-ANP-(4-23) significantly lowered MPAP in hypoxic rats but not in air controls. A statistically insignificant reduction in mean systemic arterial pressure was found in both groups after C-ANP-(4-23) administration. C-ANP-(4-23) significantly (two- to threefold) increased endogenous plasma ANP levels in both groups; the increase was not significantly different between groups. Both basal and post-C-ANP-(4-23) levels of plasma ANP were greater in hypoxia-adapted animals than in air controls; the C-ANP-induced increase in plasma ANP was not significantly different between groups. These results suggest that the endogenous ANP may modulate pulmonary vascular tone in rats with hypoxic pulmonary hypertension.
authors.affiliation: Department of Medicine, University of Alabama, Birmingham 35294.
authors.forename: H
authors.initials: H
authors.lastname: Jin
authors.forename: Y F
authors.initials: YF
authors.lastname: Chen
authors.forename: R H
authors.initials: RH
authors.lastname: Yang
authors.forename: R M
authors.initials: RM
authors.lastname: Jackson
authors.forename: S
authors.initials: S
authors.lastname: Oparil
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology* / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000503:physiopathology; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology*; D011652:Pulmonary Circulation / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D017461:Receptors, Atrial Natriuretic Factor; D011956:Receptors, Cell Surface / Q000187:drug effects* / Q000502:physiology
chemical_list: D010446:Peptide Fragments; D011956:Receptors, Cell Surface; C065367:atrial natriuretic factor (4-23)NH2, de-Gln(18)-de-Ser(19)-de-Gly(20,22)-de-Leu(21)-; D009320:Atrial Natriuretic Factor; D017461:Receptors, Atrial Natriuretic Factor