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 end-diastolic external diameter of the left ventricle by 2.6% (p less than 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 less than 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 less than 0.001), cardiopulmonary blood volume was elevated by 30% (p less than 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 renin-angiotensin system.
Finckh
M
M
Institute of Applied Physiology, University of Freiburg, FRG.
Hellmann
W
W
Ganten
D
D
Furtwängler
A
A
Allgeier
J
J
Boltz
M
M
Holtz
J
J
D000808:Angiotensinogen / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D002303:Cardiac Output, Low / Q000378:metabolism*; D002304:Cardiac Pacing, Artificial; D005786:Gene Expression Regulation; D006439:Hemodynamics; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains
D012333:RNA, Messenger; D000808:Angiotensinogen; D007703:Peptidyl-Dipeptidase A