Factors derived from adrenals are required for activation of cardiac gene expression in angiotensin II-induced hypertension

The mechanisms mediating the activation of cardiac gene expression during p ressure overload are not fully understood. We examined whether angiotensin II-induced activation of ventricular gene expression is related to blood pr essure and ventricular mass or requires other factors by infusing angiotens in II in sham-operated and adrenalectomized rats. In sham-operated rats, an giotensin II (33,mug/kg.h, sc) produced a significant increase in mean arte rial pressure (measured by telemetry) within 3 h. Mean arterial pressure (u p to 45 h) and the increase in left ventricular hypertrophy in adrenalectom ized rats during angiotensin II infusion were similar to those in sham-oper ated rats. Angiotensin II produced 3.6-fold (P < 0.01) and 20.4-fold (P < 0 .001) increases in ventricular atrial natriuretic peptide mRNA levels at 12 and 72 h, respectively. Angiotensin II infusion for 12 h also significantl y increased the ventricular mRNA levels of B-type natriuretic peptide (5.2- fold) and adrenomedullin (1.4-fold). Adrenalectomy either abolished (atrial natriuretic peptide and adrenomedullin) or blunted (B-type natriuretic pep tide) the early activation of ventricular gene expression by angiotensin II . The baseline synthesis of atrial natriuretic peptide, B-type natriuretic peptide, and adrenomedullin in the ventricle remained unchanged in adrenale ctomized rats. In conclusion, our results indicate that factors derived fro m the adrenals are required for angiotensin II-induced early activation of cardiac gene expression.