CHANGES OF ATRIAL-NATRIURETIC-PEPTIDE AND ITS MESSENGER-RNA WITH DEVELOPMENT AND REGRESSION OF CARDIAC-HYPERTROPHY IN RENOVASCULAR HYPERTENSIVE RATS

We assessed the changes in atrial natriuretic peptide (ANP) and its messenger RNA (mRNA) levels in atria and ventricles in relation to hemodynamic factors during antihypertensive treatments in two-kidney, one-clip renovascular hypertensive rats (RHRs). Hypertension of 10-week duration caused a twofold increase in the left ventricular weight/body weight ratio, a significant increase in left ventricular end-diastolic pressure, and an eightfold increase in left ventricular ANP mRNA levels in RHRs, as compared with the levels in control rats. Uninephrectomy or 4 weeks of treatment with the converting enzyme inhibitor enalapril reduced the blood pressure to the control level, with the complete reversal of left ventricular hypertrophy, left ventricular end-diastolic pressure, and ANP mRNA levels. Four weeks of treatment with the arterial vasodilator hydralazine significantly, but not completely, reduced the high blood pressure, but it did not influence left ventricular hypertrophy, end-diastolic pressure, and ANP mRNA levels. The increased ANP synthesis observed in the right ventricles of RHRs also reverted to the control level by uninephrectomy or enalapril treatment, but not by hydralazine, with a time course similar to that of left ventricular ANP. In addition, uninephrectomy caused the left and right ventricular ANP and ANP mRNA levels of RHRs to fall to the levels of control rats as early as 1 week, despite persistent left ventricular hypertrophy. The left ventricular ANP levels were closely correlated with the degree of left ventricular hypertrophy (r = 0.86, p < 0.001, n = 50), plasma ANP levels (r = 0.82, p < 0.001, n = 50, and the left ventricular end-diastolic pressure (r = 0.74, p < 0.001, n = 50). There were no such correlations for right ventricles. Taken together, we suggest that an increase in ventricular filling pressure rather than hypertension plays a more important role in the regulation of the ventricular ANP response, and we demonstrated that the ventricular ANP response in cardiac hypertrophy can be readily reversed by effectively eliminating causative stimuli.