ACTIVATION OF ANP SYNTHESIS DURING CONGESTIVE-HEART-FAILURE IN RATS TREATED WITH MONOCROTALINE

We studied plasma concentration, content, and mRNA for atrial natriure tic peptide (ANP-mRNA) in heart chambers of monocrotaline-treated rats . Three distinct groups emerged: group 1, with moderate congestive hea rt failure (CHF; pleural effusion < 1 ml; no peritoneal effusion); gro up 2, with severe CHF (pleural and peritoneal effusion > 1 ml); and gr oup 3, with right hypertrophy and no CHF. Group 1 and 2 rats had right atrial and ventricular hypertrophy, raised plasma ANP (from 16.31 +/- 11.32 to 98.50 +/- 22.50 and 124.09 +/- 57.29 pg/ml, respectively; P < 0.001), and depletion of right atrial ANP (from 143.23 +/- 29.79 to 21.70 a 17.70 and 18.12 +/- 14.64 nmol/g, respectively; P < 0.001). Ve ntricular ANP concentration was unchanged. ANP-mRNA rose in the right atrium [10.6 (P < 0.02) and 7.9 (P < 0.01) times] and right ventricle (53.0 and 46.6 times; P < 0.01). In left unhypertrophied chambers it a lso increased, although to a smaller extent. Group 3 rats had isolated right ventricular hypertrophy, normal ANP levels in plasma and tissue s, and no activation of synthesis. These data suggest that 1) plasma c oncentration and ANP synthesis are increased only in animals with CHF, 2) activation of ANP synthesis is maximal in early stages of CHF and is not related to the degree of hypertrophy, and 3) ANP-mRNA is also e xpressed in unhypertrophied heart chambers of rats with CHF but is not expressed in hypertrophied chambers of animals without CHF.