Cardiac myocyte necrosis induced by angiotensin II

L. B. Tan, J. E. Jalil, R. Pick, J. S. Janicki, Karl Weber

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Abstract

Although the role of angiotensin II (Ang II) in the pathogenesis and progression of the failing heart is uncertain, previous reports have suggested that myocyte injury may be a component in this process. In this study, we investigated this possibility in more detail. Cardiotoxic effects of nonacutely hypertensive doses of Ang II were examined in 90 rats, including those receiving an angiotensin infusion (200 ng/min i.p.) and those with renovascular hypertension, where endogenous stimulation of Ang II occurred. Myocyte injury and wound healing resulting from these treatments were evaluated by 1) immunofluorescence after in vivo monoclonal antibody labeling of myosin to detect abnormal sarcolemmal permeability, 2) [3H]thymidine incorporation into DNA, to detect fibroblast proliferation, and 3) light microscopic evidence of myocytolysis and subsequent scar formation. We found that exogenous Ang II produced multifocal antimyosin labeling of cardiac myocytes and myocytolysis, which were maximal on days 1-2 of the infusion. Subsequently, DNA synthesis rates were increased, with fibroblast proliferation reaching peak levels on day 2 (Ang II-treated rats, 90.0±18.6 cpm/μg DNA; control rats, 11.4±2.3 cpm/μg DNA; p<0.05); microscopic scarring was found on day 14 and represented 0.12±0.02% of the myocardium. Concurrent treatment with both propranolol (30 mg/kg/day s.c.) and phenoxybenzamine (5 mg/kg/day i.m.) did not attenuate Ang II-induced antimyosin labeling. Increased endogenous Ang II, resulting from renal ischemia after abdominal aortic constriction, produced both antimyosin labeling and increased rates of DNA synthesis like that observed with Ang II infusion. Both myocyte injury and fibroplasia were prevented with captopril (65 mg/day p.o.), but this protective effect was not seen with reserpine pretreatment. Infrarenal aortic banding without renal ischemia, on the other hand, produced hypertension without necrosis. We conclude that pathophysiological levels of endogenous as well as low-dose exogenous Ang II were associated with altered sarcolemmal permeability and myocytolysis with subsequent fibroblast proliferation and scar formation. Myocyte injury was unrelated to the hypertensive or enhanced adrenergic effects of Ang II or to hypertension per se. Captopril was effective in preventing myocyte injury in renovascular hypertension. The mechanism(s) responsible for Ang II-induced necrosis will require further study.

Original languageEnglish (US)
Pages (from-to)1185-1195
Number of pages11
JournalCirculation research
Volume69
Issue number5
DOIs
StatePublished - Jan 1 1991

Fingerprint

Cardiac Myocytes
Angiotensin II
Necrosis
Muscle Cells
DNA
Wounds and Injuries
Cicatrix
Renovascular Hypertension
Fibroblasts
Captopril
Permeability
Ischemia
Hypertension
Kidney
Phenoxybenzamine
Reserpine
Angiotensins
Myosins
Constriction
Propranolol

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Cardiac myocyte necrosis induced by angiotensin II. / Tan, L. B.; Jalil, J. E.; Pick, R.; Janicki, J. S.; Weber, Karl.

In: Circulation research, Vol. 69, No. 5, 01.01.1991, p. 1185-1195.

Research output: Contribution to journalArticle

Tan, LB, Jalil, JE, Pick, R, Janicki, JS & Weber, K 1991, 'Cardiac myocyte necrosis induced by angiotensin II', Circulation research, vol. 69, no. 5, pp. 1185-1195. https://doi.org/10.1161/01.RES.69.5.1185
Tan, L. B. ; Jalil, J. E. ; Pick, R. ; Janicki, J. S. ; Weber, Karl. / Cardiac myocyte necrosis induced by angiotensin II. In: Circulation research. 1991 ; Vol. 69, No. 5. pp. 1185-1195.
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