Pathogenesis and management of sodium and water retention in cardiac failure and cirrhosis

ArticleinSeminars in Nephrology 21(2):157-72 · April 2001with4 Reads
Impact Factor: 3.48 · DOI: 10.1053/snep.2001.20933 · Source: PubMed

The kidneys play the crucial role in the maintenance of the body fluid volume homeostasis. Several hypotheses have been introduced to explain sodium and water retention leading to edematous states in such pathologic conditions as congestive heart failure (CHF) and cirrhosis. We have suggested a unifying arterial underfilling hypothesis, explaining the development of edema in these conditions. Arterial underfilling, caused by decreased cardiac output or peripheral arterial vasodilation, leads to activation of the sympathetic nervous system, renin-angiotensin-aldosterone system, and nonosmotic vasopressin release. This review discusses the pathophysiologic mechanisms resulting in renal sodium and water retention, impaired mineralocorticoid escape, and resistance to atrial natriuretic peptide in patients with CHF and cirrhosis. Furthermore, the basis of current therapies in these disorders is discussed, including beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, aldosterone antagonists, and diuretics in CHF and cirrhosis, as well as new approaches to treatment of water retention with vasopressin V(2) receptor antagonists.

    • "According to this, the underfilling due to low cardiac output or peripheral vasodilation leads to activation of sympathetic nervous system and nonosmotic arginine vasopressin release. Consequently, diminished water and sodium delivery at collecting duct sites in addition to renal adrenergic activity induces renin angiotensin aldosterone system, which enhances tubular reabsorption [1,456. The cortical collecting tubules are the primary site to contribute to the edema formation in nephrotic syndrome. "
    [Show abstract] [Hide abstract] ABSTRACT: Diuretics play significant role in pharmacology and treatment options in medicine. This paper aims to review and evaluate the clinical use of diuretics in conditions that lead to fluid overload in the body such as cardiac failure, cirrhosis, and nephrotic syndrome. To know the principles of treatment it is essential to understand the underlying pathophysiological mechanisms that cause the need of diuresis in the human body. Various classes of diuretics exist, each having a unique mode of action. A systemic approach for management is recommended based on the current guidelines, starting from thiazides and proceeding to loop diuretics. The first condition for discussion in the paper is cardiac failure. Treatment of ascites in liver cirrhosis with spironolactone as the primary agent is highlighted with further therapeutic options. Lastly, management choices for nephrotic syndrome are discussed and recommended beginning from basic sodium restriction to combined diuretic therapies. Major side effects are discussed.
    Full-text · Article · Jul 2015 · International Journal of Nephrology
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    • "In addition, activation of vasopressin V 2 receptors causes retention of water and edema, further exacerbating heart function. Vasopressin V 2 -mediated water retention in heart failure can occur in the absence of a hyperosmotic stimulus, possibly due to renal underperfusion as a result of inadequate cardiac function (Schrier et al., 2001). Thus, hyponatremia often accompanies the edema of heart failure, suggesting a particular advantage of the sodium sparing actions of blocking vasopressin V 2 receptors over conventional diuretics in these situations (Goldsmith, 2006). "
    [Show abstract] [Hide abstract] ABSTRACT: The dysregulation of arginine vasopressin (AVP) release and activation of vasopressin V(1A) and V(2) receptors may play a role in disease. The in vitro and in vivo pharmacology of RWJ-676070, a potent, balanced antagonist of both the V(1A) and V(2) receptors is described. RWJ-676070 binding and intracellular functional antagonist activity was characterized using cells expressing V(1A), V(1B) or V(2) receptors. Its inhibition of V(1A) receptor-mediated contraction of vascular rings and platelet aggregation was determined. V(2) receptor-medated aquaresis was determined in rats, dogs and monkeys. V(1A) receptor-mediated inhibitory activity was assessed in vivo in a vasopressin-induced hypertension model and in normotensive rats and in two hypertensive rat models. RWJ-676070 inhibited AVP binding to human V(1A) and V(2) receptors (Ki=1 and 14 nM, respectively). RWJ-676070 inhibited V(1A) receptor-induced intracellular calcium mobilization and V(2) receptor-induced cAMP accumulation with Ki values of 14 nM and 13 nM, respectively. The compound was slightly less potent against rat V(1A) receptors. RWJ-676070 inhibited V(1A) receptor-mediated vasoconstriction in rat and dog vascular rings and AVP-induced human platelet aggregation. Dose dependent aquaresis was demonstrated in rats, dogs and monkeys following oral administration. RWJ-676070 inhibited AVP-induced hypertension in rats but had no effect on arterial pressure in normotensive and spontaneously hypertensive rats but did decrease arterial pressure in Dahl, salt-sensitive hypertensive rats. RWJ-676070 is a new, potent antagonist of V(1A) and V(2) receptors that may be useful for treatment of diseases benefiting from balanced inhibition of both V(1A) and V(2) receptors.
    Full-text · Article · Jul 2008 · European Journal of Pharmacology
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    • "Increased activity of the vasoconstrictor systems may also lead to salt and water retention by the kidney, and thereby cause a further deterioration in cardiac performance[10] [27]. In addition, the RAAS, catecholamines and other vasoconstrictor agents are involved in the induction of cardiac hypertrophy in CHF[21] [33]. "
    [Show abstract] [Hide abstract] ABSTRACT: Rho-dependent kinases serve as downstream effectors of several vasoconstrictor systems, the activities of which are upregulated in congestive heart failure (CHF). We evaluated renal and cardiac effects of Y-27632, a highly selective Rho kinase inhibitor, in an experimental model of volume-overload CHF. Effects of acute administration of Y-27632 (0.3 mg/kg) on renal hemodynamic and clearance parameters and effects of chronic treatment (10.0 for 7 days via osmotic minipumps) on cardiac hypertrophy and cumulative Na+ excretion were studied in male Wistar rats with aortocaval fistula and control rats. The Y-27632-induced decrease in renal vascular resistance (from 40.4 +/- 4.6 to 26.0 +/- 3.1 resistance units, P < 0.01) in CHF rats was associated with a significant increase in total renal blood flow (+34%) and cortical and medullary blood flow (approx +37 and +27%, respectively). These values were significantly higher than those in control rats and occurred despite a decrease in mean arterial pressure (-15 mmHg). Despite the marked renal vasodilatory effect, Y-27632 did not alter glomerular filtration rate and renal Na+ excretion. Chronic administration of Y-27632 did not alter daily or cumulative renal Na+ excretion in CHF rats but was associated with a significant decrease in heart-to-body weight ratio, an index of cardiac hypertrophy: 0.32 +/- 0.007, 0.46 +/- 0.017, and 0.37 +/- 0.006% in control, CHF, and CHF + Y-27632 rats, respectively. The findings suggest that Rho kinase-dependent pathways are involved in the mechanisms of renal vasoconstriction and cardiac hypertrophy in rats with volume-overload heart failure. Selective blockade of these signaling pathways may be considered an additional tool to improve renal perfusion and attenuate cardiac hypertrophy in heart failure.
    Full-text · Article · Jun 2006 · AJP Heart and Circulatory Physiology
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