In low-output states, activation of the renin-angiotensin system operates in concert with the activated adrenergic nervous system and adrenal medulla to maintain blood pressure and retain sodium and water. These two compensatory systems are clearly coupled. Heightened adrenergic drive to the (ij-adrenoceptors in the renal juxtaglomerular apparatus is the main mechanism behind renin release in acute heart failure. Activation of the baroceptors in the renal vascular bed by a decrease in renal blood flow also releases renin, as does a decrease in the sodium presented to the macula densa in salt-restricted patients with severe heart failure on diuretic therapy. Elevated plasma renin activity is a common, although not universal, finding in heart failure. In the Studies Of Left Ventricular Dysfunction (SOLVD), plasma angiotensin II was significandy elevated even in asymptomatic patients and was further elevated in patients with symptomatic heart failure. Angiotensin II is a potent peripheral vasoconstrictor and contributes, along with increased adrenergic activity, to the excessive elevation of systemic vascular resistance. It also enhances norepinephrine release by the adrenergic nervous system. Aldosterone has potent sodium-retaining properties and contributes to the development of edema. Thus, it is not surprising that interruption of the renin-angiotensin-aldosterone axis using an angiotensin-converting enzyme (ACE) inhibitor should lower
Braunwald E, Bristow MR. Congestive heart failure: fifty years of progress. Circulation. 2000;102:IV14-IV23. systemic vascular resistance (afterload) and elevate cardiac output in heart failure.
In some patients, ACE inhibitors are also mild diuretics, presumably by lowering the angiotensin II-stimulated production of aldosterone. Angiotensin II may also play a direct role in modifying myocardial structure and function. In cardiac myocytes in culture, it causes cellular hypertrophy, fetal gene induction, and apoptosis. It also appears to play a role in mediating the apoptotic effect of mechanical strain and is a potent stimulator of several signaling pathways, including those involved in the regulation of the extracellular matrix.
Aldosterone plays an important role in cardiac remodeling, fibroblast proliferation, and collagen deposition. These changes increase the passive stiffness of the ventricles and arterial bed, interfere with ventricular filling, and decrease arterial compliance. Elevated circulating aldosterone levels predict adverse outcome in heart failure patients.
There is increasing evidence of cross-talk between the adrenergic and renin-angiotensin-aldosterone systems. Aldosterone decreases the neuronal reuptake of norepinephrine and thereby facilitates the emergence of cardiac arrhythmias. In heart failure, ACE inhibition lowers peripheral sympathetic nerve impulse traffic and cardiac adrenergic drive, and is most beneficial in patients in whom adrenergic activation is most prominent.
Braunwald E, Zipes DP, Libby P, eds. Heart Disease: A Textbook of Cardiovascular Medicine. 6th ed. Philadelphia, Pa: WB Saunders; 2001.
drug; renin-angiotensin system; ACEI; aldosterone