ENHANCED CARDIAC ANGIOTENSINOGEN GENE-EXPRESSION AND ANGIOTENSIN CONVERTING ENZYME-ACTIVITY IN TACHYPACING-INDUCED HEART-FAILURE IN RATS

The aim of the study was to analyze changes in myocardial angiotensinogen gene expression and myocardial angiotensin converting enzyme activity in slowly progressing low-output failure. In adult, male Wistar rats, acute ventricular tachypacing by 610 to 620 impulses per minute lowered enddiastolic external diameter of the left ventricle by 2.6% (p < 0.01), but did not lower cardiac output or abolish coronary reserve, since left-ventricular subendocardial blood flow of paced rats increased under dipyridamole (2 mg/kg i.v.) by 56% (p < 0.01). Systemic neuroendocrine activation and ventricular dilation without enlargement of ventricular mass developed subsequent to chronic tachypacing, but left-ventricular diameter during pacing never exceeded the value of sham rats on sinus rhythm. After 2 weeks, cardiac output was lowered by 14% (p < 0.001), cardiopulmonary blood volume was elevated by 30% (p < 0.001), and angiotensinogen mRNA and angiotensin converting enzyme activity in ventricular myocardium were doubled. We conclude that conditions for an enhanced intracardiac angiotensin II-formation developed in tachypacing-induced heart failure, but that enhanced systolic wall stress or myocardial ischemia are not required for this activation of the local cardiac reninangiotensin system.