Tissue Renin-Angiotensin Systems in the Pathophysiology of Heart Failure

  • A. T. Hirsch
  • V. J. Dzau
Conference paper


It is well documented that a reduction in cardiac output elicits compensatory homeostatic responses that are mediated by neurohormonal mechanisms. Activation of the sympathetic nervous system results in systemic vasoconstriction, decreases in renal blood flow and glomerular filtration rate, and an increase in tubular reabsorption of sodium [1]. Activation of the renin-angiotensin system (RAS) contributes further to the increases in vascular tone and sodium avidity. While vasopressin secretion may also be increased during marked reductions in cardiac output, it is unlikely that this hormone contributes significantly to the maintainance of systemic vasoconstriction, as compared to its effects on sodium and water homeostasis [2–4]. The temporal activation of circulating neurohormonal mechanisms are well-illustrated by the study of Watkins et al., in the experimental canine model of cardiac decompensation [5]. In this model, reductions in cardiac output and filling pressure result in the elevations of plasma renin activity and angiotensin II (All) aldosterone, norepinephrine, and vasopressin levels that are associated with vasoconstriction and sodium retention. However, these circulating neurohormonal mechanisms return toward normal during the compensated stage of heart failure as plasma volume and cardiac stroke volume increase. Thus, in experimental heart failure, circulating neurohormonal mechanisms exhibit a time-dependent response, with acute activation and subsequent normalization during the chronic, compensated phase (Fig. 1).


Angiotensin Converting Enzyme Plasma Renin Activity Serum Angiotensin Converting Enzyme Renin mRNA Experimental Heart Failure 
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© Springer-Verlag Berlin Heidelberg 1990

Authors and Affiliations

  • A. T. Hirsch
  • V. J. Dzau

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