CORONARY PRESSURE AS A DETERMINANT OF B-TYPE NATRIURETIC PEPTIDE GENE-EXPRESSION IN ISOLATED-PERFUSED ADULT-RAT HEART

The role of coronary flow in the regulation of ventricular B-type natr iuretic peptide (BNP) gene expression was studied in isolated perfused rat heart preparation. The increase of coronary flow from 5 ml/min to 20 ml/min for 2 h resulted in a 132+/-6 mm Hg increase in aortic perf usion pressure. The changes in BNP mRNA and immunoreactive BNP (IR-BNP ) levels in response to hemodynamic stress were compared to those of c -fos and adrenomedullin (ADM) gene expression. The increase of coronar y flow resulted in 1.5-fold increases in the left ventricular BNP mRNA (P < 0.001) and IR-BNP (P < 0.05) levels in 2-month old rats. There w as also a 1.5-fold (P < 0.05) increase in ventricular c-fos mRNA level s, whereas ADM mRNA levels decreased by 74 % (P < 0.001) in the left v entricle. In 18-month old rats, the increase in coronary flow decrease d left and right ventricular BNP mRNA levels by 18 % (P < 0.05) and 39 % (P < 0.001), respectively. There were no changes in IR-BNP peptide and c-fos mRNA levels, whereas ADM mRNA levels decreased by 46 % (P < 0.001) in the left ventricles. The results show that increased aortic perfusion pressure results in differential expression of cardiac genes including up-regulation of ventricular BNP and c-fos gene expression and down-regulation of ADM gene expression. Furthermore, aging seems t o elevate the threshold at which hemodynamic stress of the heart resul ts in a response at BNP gene level.