Enhanced activity of the cardiac endocrine system during right ventricular hypertrophy

In a model of pulmonary hypertension induced by a single injection of monocrotaline (MCT), we observed a time-dependent right ventricular hypertrophy, which became apparent in treated rats 21 days after administration of MCT and progressed through day 45. Associated with this right ventricular hypertrophy were time-dependent increases in ventricular levels of immunoreactive atrial natriuretic peptide (iANP). Forty-five days after MCT treatment, treated rats exhibited a 72-fold increase in right ventricular iANP levels and a 7-fold increase in left ventricular iANP levels. Hybridization analysis of total RNA extracted from cardiac tissue indicated that both atrial and ventricular ANP mRNA levels were elevated in treated rats. These data suggest that during pulmonary hypertension and cardiac hypertrophy the endocrine activity of the heart expands to include ventricular tissue. ANP binding site autoradiography revealed decreased binding site density in the kidney and hearts of treated rats at 49 days, consistent with the occurrence of desensitization/down-regulation. Enhanced ventricular ANP production may serve as a compensatory response to sustained elevation of pulmonary arterial pressure or may function as an autocrine/paracrine system regulating cardiac function. In either case, the effects of augmented ANP production may be subject to modulation by the status of ANP receptors in target organs and cells.