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Regulation of intrarenal and circulating renin-angiotensin systems in severe heart failure in the rat.

Publication ,  Journal Article
Schunkert, H; Tang, SS; Litwin, SE; Diamant, D; Riegger, G; Dzau, VJ; Ingelfinger, JR
Published in: Cardiovasc Res
May 1993

OBJECTIVE: Activation of the intrarenal renin-angiotensin system may contribute to the pathophysiology of heart failure by accelerating the generation of angiotensin II at local sites within the kidneys. Activation of the local intrarenal renin-angiotensin system occurs in rats and with mild heart failure. The aim of the present study was to examine components of the circulating as well as the intrarenal renin-angiotensin system in rats with severe heart failure. METHODS: Six weeks after experimental myocardial infarction (heart failure, HF; n = 8) or sham operation (control, C; n = 6), haemodynamics and the circulating and intrarenal components of the renin-angiotensin system were studied. RESULTS: HF rats were characterised by large infarctions (scar tissue > 40% of the left ventricular circumference). In comparison to sham operated controls, large myocardial infarctions resulted in severe heart failure with decreased systolic [108(SEM 3) mm Hg v 132(3) in C; p < 0.001] and diastolic arterial blood pressure [83(3) mm Hg v 95(2) in C; p < 0.05], decreased left ventricular systolic pressure [109(3) mm Hg v 132(3) in C; p < 0.005] and increased left ventricular end diastolic pressure [27(2) mm Hg v 5(1) in C; p < 0.0001]. In rats with severe heart failure, the circulating renin-angiotensin system was activated, with an increase in plasma renin activity (3.5-fold, p < 0.05) and plasma angiotensin II concentration (threefold, p < 0.01). In parallel, the intrarenal renin-angiotensin system was activated in severe heart failure. Increases occurred in renal renin mRNA level (1.7-fold, p < 0.01), renal angiotensinogen mRNA level (1.8-fold, p < 0.05), and renal angiotensin II concentration (twofold, p < 0.05) compared to C. Intrarenal angiotensin II concentrations exceeded plasma levels by a factor of 50 and were positively correlated with renal angiotensinogen mRNA levels (r = 0.874, p < 0.001), suggesting that local synthesis is the major source of angiotensin II found in the kidney. CONCLUSIONS: The intrarenal renin-angiotensin system may be selectively activated in mild heart failure, while both circulating and intrarenal renin-angiotensin systems are induced as the extent of left ventricular function worsens.

Duke Scholars

Published In

Cardiovasc Res

DOI

ISSN

0008-6363

Publication Date

May 1993

Volume

27

Issue

5

Start / End Page

731 / 735

Location

England

Related Subject Headings

  • Renin-Angiotensin System
  • Renin
  • Rats, Sprague-Dawley
  • Rats
  • Myocardial Infarction
  • Male
  • Kidney
  • Heart Failure
  • Disease Models, Animal
  • Cardiovascular System & Hematology
 

Citation

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Schunkert, H., Tang, S. S., Litwin, S. E., Diamant, D., Riegger, G., Dzau, V. J., & Ingelfinger, J. R. (1993). Regulation of intrarenal and circulating renin-angiotensin systems in severe heart failure in the rat. Cardiovasc Res, 27(5), 731–735. https://doi.org/10.1093/cvr/27.5.731
Schunkert, H., S. S. Tang, S. E. Litwin, D. Diamant, G. Riegger, V. J. Dzau, and J. R. Ingelfinger. “Regulation of intrarenal and circulating renin-angiotensin systems in severe heart failure in the rat.Cardiovasc Res 27, no. 5 (May 1993): 731–35. https://doi.org/10.1093/cvr/27.5.731.
Schunkert H, Tang SS, Litwin SE, Diamant D, Riegger G, Dzau VJ, et al. Regulation of intrarenal and circulating renin-angiotensin systems in severe heart failure in the rat. Cardiovasc Res. 1993 May;27(5):731–5.
Schunkert, H., et al. “Regulation of intrarenal and circulating renin-angiotensin systems in severe heart failure in the rat.Cardiovasc Res, vol. 27, no. 5, May 1993, pp. 731–35. Pubmed, doi:10.1093/cvr/27.5.731.
Schunkert H, Tang SS, Litwin SE, Diamant D, Riegger G, Dzau VJ, Ingelfinger JR. Regulation of intrarenal and circulating renin-angiotensin systems in severe heart failure in the rat. Cardiovasc Res. 1993 May;27(5):731–735.
Journal cover image

Published In

Cardiovasc Res

DOI

ISSN

0008-6363

Publication Date

May 1993

Volume

27

Issue

5

Start / End Page

731 / 735

Location

England

Related Subject Headings

  • Renin-Angiotensin System
  • Renin
  • Rats, Sprague-Dawley
  • Rats
  • Myocardial Infarction
  • Male
  • Kidney
  • Heart Failure
  • Disease Models, Animal
  • Cardiovascular System & Hematology