ATRIAL-NATRIURETIC-PEPTIDE EXPRESSION IN RATS WITH DIFFERENT PULMONARY HYPERTENSIVE RESPONSES TO HYPOXIA

Mechanisms that regulate atrial natriuretic peptide (ANP) expression d uring hypoxia are not well defined. We hypothesized that plasma immuno reactive ANP (irANP) and right heart irANP and ANP mRNA levels would b e greater in a strain of Sprague-Dawley rats that develops more severe hypoxic pulmonary hypertension (H rats) than another strain (M rats). After 3 wk of hypoxia (0.5 atm), right ventricular systolic pressure (RVSP) and the right ventricle (RV) weight-to-left ventricle plus sept um (LV+S) weight ratio [RV/(LV+S)] were greater in H rats than in M ra ts (70 +/- 4 vs. 40 +/- 2 mmHg and 0.59 +/- 0.02 vs. 0.50 +/- 0.02, re spectively; P < 0.05 for both), but plasma ANP increased twofold and R V irANP and ANP mRNA increased fivefold in both rat strains. After 3 d ays of normoxic recovery from chronic hypoxia, RVSP, RV/(LV+S), and RV irANP and ANP mRNA levels decreased in M rats but not in H rats. Plas ma irANP decreased to baseline levels in both rat strains. We conclude that, in addition to changes in RV pressure and hypertrophy, hypoxia acts through other mechanisms to modulate RV ANP synthesis and circula ting ANP levels in hypoxia-adapted rats.