Angiotensin II in the Evolution of Experimental Heart Failure

Abstract

Although angiotensin II (Ang II) has been implicated in the pathophysiology of congestive heart failure, its temporal and regional changes during the development and progression of the disease are poorly defined. Our objective was to assess circulating, renal, cardiac, and vascular Ang II in a canine model of rapid ventricular pacing-induced heart failure that evolves from early left ventricular dysfunction to overt congestive heart failure. Ang II was measured by radioimmunoassay with low cross-reactivity to other angiotensins. Control, early left ventricular dysfunction, and overt congestive heart failure dogs were studied. Early left ventricular dysfunction was characterized by impaired cardiac function, cardiac enlargement, preserved renal perfusion pressure, maintained urinary sodium excretion, and normal plasma renin activity. Overt congestive heart failure was characterized by further impaired cardiac function and cardiac enlargement, reduced renal perfusion pressure, urinary sodium retention, and increased plasma renin activity and plasma Ang II. In early left ventricular dysfunction dogs, renal cortical, renal medullary, ventricular, and aortic Ang II were unchanged, and atrial Ang II was decreased. In overt congestive heart failure dogs, Ang II was increased in the kidney and heart compared with normal dogs and in all tissues compared with early left ventricular dysfunction dogs. The greatest increase in tissue Ang II occurred in the renal medulla. We conclude that early increases in local renal, myocardial, and vascular Ang II do not occur in this model of early left ventricular dysfunction and may even be suppressed. In contrast, increased myocardial and particularly renal Ang II in association with increased circulating Ang II are hallmarks of overt experimental congestive heart failure. These studies provide new insights into the temporal and regional alterations in Ang II during the progression of experimental congestive heart failure.

Angiotensin II AT1 receptor antagonism prevents detrimental renal actions of acute diuretic therapy in human heart failure

“…Although increased circulating and tissue ANG II in CHF has been demonstrated, recent studies from our laboratory by Luchner et al (7) established that throughout the evolution of CHF, renal ANG II concentrations exceed concentrations in other tissues. This observation further supports the importance of ANG II as a major factor in mediating renal vasoconstriction and enhanced sodium reabsorption in CHF.…”

Myocardial oxidative stress changes during compensated right heart failure in rats

“…Stimulation of the adrenergic (Hauser et al 1996, Xiong et al 1996, Anfossi and Trwati 1996, Kinugawa et al-1996, and reninangiotensin-aldosterone systems, as weii as other neurohumoral adjustments can act to maintain arterial pressure and thus perfusion to vital organs (Teerlink 1996, Kato et al 1996. Activation of the renin-angiotensinaldosterone system also increases Ouid retention, which acts as a compensatory mechanism to maintain arterial blood pressure and cardiac output (Luchner et al 1996).…”

“…Lower cardiac output then eücits renal responses inciuding increased water and Na+ retention and vasoconstriction that initially helps to maintain artenal blood pressure and tissue pemision (Luchner et al 1996).…”

Cardiotrophin-1 Stimulation of Cardiac Fibroblast Growth

“…It should be noted that it remains unknown whether the in vitro data in the current study can be extended to the in vivo situation. Our study in a canine model of early dilated cardiomyopathy produced by progressively increasing pacing rates (180 to 200 bpm for approximately 14 to 20 days) 38 demonstrates that ventricular CT-1 and gp130 are decreased and LIF receptor is enhanced, as compared with normal, by immunohistochemical staining (data not shown). Considering the important role of cardiac fibroblasts, which maintain the structure of the heart, this in vivo finding suggests that impaired CT-1 protein and gp130 axis in this model could contribute to progressive ventricular remodeling.…”