Regulation of ventricular atrial natriuretic peptide release in hypertrophied rat myocardium. Effects of exercise.

Abstract

Left ventricular hypertrophy is characterized by stimulation of ventricular synthesis of atrial natriuretic peptide (ANP). This study was designed to test the hypothesis that the increased ventricular ANP levels participate in the release of ANP into the circulation. Swimming was used as a physiologic model to induce ANP release from the heart, and atrial and ventricular levels of immunoreactive ANP (IR-ANP) and ANP messenger RNA (mRNA) were measured simultaneously in the spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats at rest and after swimming. IR-ANP concentration in the left ventricle of 1-year-old SHR with severe left ventricular hypertrophy was increased in association with the augmentation of ANP mRNA levels, whereas right ventricular levels of ANP were reduced in SHR compared with normotensive controls. A 30-minute exercise in hypertensive and in normotensive rats resulted in marked increases in mean arterial pressure, heart rate, plasma catecholamine levels, blood lactate levels, and plasma IR-ANP concentration. The increased ANP secretion was associated with a decrease in left (34-39%) and right (24%) ventricular concentration of IR-ANP; transmurally, this depletion of ventricular IR-ANP was greatest (28%) in the endocardial layer of the left ventricle of SHR. No significant differences were noted in total atrial and left or right auricular IR-ANP concentration between SHR and WKY rats or between the resting and swimming rats. When studied in vitro with an isolated, perfused heart preparation, the hypertrophic ventricular tissue after atrialectomy secreted more ANP into the perfusate than did control hearts; in SHR, ventricles contributed 28% of the total ANP release to perfusate, and in normotensive control rats, ventricles contributed 8%. These studies show that stimulated release of ANP is associated with depletion of endocardial left ventricular stores. The amount of ANP released in vitro and in vivo correlated with the degree of hypertrophy of the ventricle. Finally, the phorbol ester, known to increase ANP secretion from intact perfused hearts, had only a limited effect on ANP release after atrialectomy, suggesting that the secretion of ANP from ventricular cells may be mainly of the constitutive type.