The renal sodium and water retention that occurs with advanced left ventricular failure is associated with substantial morbidity and mortality. This sodium and water retention, which can lead to pulmonary edema, pleural effusion, and peripheral edema, occurs despite an increase in total blood volume. In normal individuals, a rise in total blood volume increases renal sodium and water excretion. The kidney is intrinsically intact with left ventricular failure, because the renal sodium and water retention does not persist after a successful heart transplant.
This seeming paradox of increased blood volume yet renal sodium and water retention in cardiac failure has been explained by the body fluid volume regulation hypothesis (1–3). This hypothesis proposes that the kidney does not respond to changes in total blood volume but rather responds to what has been termed effective arterial blood volume. In general terms, approximately 85% of circulating blood volume is in the low-pressure venous side of the circulation, whereas only 15% is in the high-pressure arterial circulation. The integrity of the arterial circulation depends on cardiac output and systemic vascular resistance and is modulated by arterial stretch baroreceptors in the carotid sinus, aortic arch, and afferent arteriole of the glomerulus (4). Thus, despite an increase in total blood volume, arterial underfilling can occur secondary to a decrease in cardiac output in low-output heart failure or decreased systemic vascular resistance in high-output heart failure. With arterial underfilling secondary to either condition, arterial baroreceptor–mediated activation of the neurohumoral axis occurs. The resultant increase in renin-angiotensin-aldosterone system (RAAS) leads to sodium retention, and the increase in the nonosmotic release of arginine vasopressin (AVP) is associated with water retention and hyponatremia in advanced left ventricular failure, a known risk factor for increased mortality (5). This water retention is due to AVP activation of the V2 vasopressin receptors on the basolateral surface of the principal cells of the collecting duct, which increases aquaporin 2 water channel expression and trafficking to the apical membrane of the collecting duct (6–8).
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There is also evidence that increased plasma AVP concentration with left ventricular failure stimulates V1 vasopressin receptors on blood vessels, which contributes, along with angiotensin II and the sympathetic nervous system, to increasing systemic vascular resistance in low-cardiac output failure (9). This arterial baroreceptor–mediated neurohumoral activation maintains arterial pressure but at the expense of renal vasoconstriction and sodium and water retention. The pathophysiology of left ventricular cardiac failure is shown in Figure 1.
These arterial baroreceptor pathways seem to override any of the low-pressure reflexes in the atria during left ventricular failure. An increase in transmural atrial pressure normally suppresses AVP and stimulates atrial natriuretic peptide (ANP), which leads to increased sodium and water excretion (10). With advanced left ventricular failure, however, left atrial pressure rises, yet sodium and water retention occurs. This suggests that activation of the arterial stretch receptors in cardiac failure predominates over any atrial pressure receptor reflex. There is also evidence that these normal atrial reflexes are blunted in patients with left ventricular failure (11).
An increase in the ventricular synthesis of brain natriuretic peptide (BNP) and, thus, circulatory BNP concentration also occurs in left ventricular failure and may attenuate the degree of renal sodium and water retention. BNP may decrease the edema formation by both suppressing the RAAS and inhibiting tubular sodium reabsorption (12).