Atrial natriuretic peptide clearance receptor agonist lowers pulmonary pressure in hypoxic rats.
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.
Jin
H
H
Department of Medicine, University of Alabama, Birmingham 35294.
Chen
Y F
YF
Yang
R H
RH
Jackson
R M
RM
Oparil
S
S
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
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