Chronic heart failure: pathophysiology and therapeutic approaches - why is the kidney so important?

The leading symptoms of severe chronic heart failure (CHF), low arterial blood pressure, dyspnoea and oedema, reflect the pathophysiological key features of CRF, i.e. arterial underfilling with subsequent sodium and water retention. Arterial underfilling is sensed by extrarenal as well as renal baroreceptors, which activate hormonal effecters such as catecholamines, the renin-angiotensin-aldosterone systems, endothelin and vasopressin. Subsequently, sodium and water retention is induced by the following renal/adrenal mechanisms: (1) reduced renal plasma flow; (2) constriction of the efferent glomerular arteriole; (3) enhanced proximal tubular sodium reabsorption; (4) enhanced distal tubular sodium reabsorption; (5) increased renal water reabsorption; (6) increased renin release; and (7) increased release of aldosterone. In early heart failure, vasoconstriction as well as renal sodium and water retention are partly counter-regulated by activation of vasodilatory and natriuretic substances, such as natriuretic peptides, prostaglandins, nitric oxide and adrenomedullin In advanced heart failure, however, vasoconstriction with Subsequent avid sodium and water retention predominates. Pharmacotherapy in CHF should aim at antagonizing the detrimental effects of neurohumoral activation The sequence of pathophysiological alterations predicts that a combined treatment with ACE inhibitors (or angiotensin II antagonists), diuretics and beta-blockers would best antagonize the activated renal/ adrenal mechanisms with avid salt and water retention. (Eur Heart J Supplements 2001; 3 (Suppl G): G3-G7) (C) 2001 The European Society of Cardiology.