it is a major cause of cardiovascular mortality and morbidity1 ) . decreased systolic or diastolic cardiac function results in abnormal circulatory hemodynamics , activation of a variety of neurohormonal systems and retention of sodium and water2 ) . the integrity of the arterial circulation is determined by cardiac output and peripheral vascular resistance . that is an important signal which triggers multiple neurohormonal systems to maintain adequate arterial pressure and peripheral perfusion of the vital organs3 ) . the kidney plays an important role in the maintenance of body fluid volume which is regulated by multiple neurohormonal systems . alterations of hemodynamics and neurohormonal systems in heart failure result in renal sodium and water retention4 ) . it has been demonstrated by an increase in plasma concentrations of catecholamine in patients with heart failure5 , 6 ) . increased catecholamine secretion plays a role in the maintenance of blood pressure in heart failure . in addition , activation of sns contributes to renal sodium and water retention in heart failure . in the kidney , sns plays a stimulatory role in renal tubular reabsorption of sodium and water7 ) . previous studies have demonstrated a direct effect of renal nerve activation on renal sodium and water reabsorption across the proximal tubular epithelium . adrenergic innervations in the basement membrane of renal tubular epithelial cells were demonstrated8 , 9 ) . low - frequency electrical stimulation of the renal nerves resulted in an antidiuretic and antinatriuretic response in the absence of changes in glomerular filtration rate ( gfr ) or renal plasma flow8 ) . moreover , the protein expression of aquaporin ( aqp ) water channels was decreased in the denervated kidney10 ) . in addition , the activation of renal nerves stimulates the renin - angiotensin - aldosterone system ( raas ) by stimulating renin release3 , 12 ) . in heart failure , angiotensin ii is an important mediator of sodium and water retention in patients with heart failure . in addition , it was demonstrated that aldosterone antagonist spironolactone increased urinary sodium excretion in patients with heart failure16 ) . in the kidney , natriuretic peptides ( nps ) increase the gfr and urinary sodium excretion by afferent arteriolar vasodilation and efferent arteriolar constriction17 ) . moreover , nps inhibit sodium and water reabsorption induced by angiotensin ii action in the proximal tubule and they directly inhibit sodium reabsorption in the collecting duct18 , 19 ) . however , the renal responses of nps were blunted in patients with heart failure23 ) . the resistance may be due to down - regulation of renal np receptors , secretion of inactive immunoreactive nps , increased degradation of nps by neutral endopeptidase in the proximal tubule or decreased sodium delivery to the collecting duct as a result of increased sodium reabsorption in the proximal tubule3 ) . arginine vasopressin ( avp ) is an antidiuretic hormone which is synthesized in the hypothalamus , stored in the posterior pituitary gland and released in response to increased osmolality or volume depletion . in the kidney , avp causes antidiuresis by activating vasopressin v2 receptors on the basolateral membrane of the principal cells in the collecting duct . this process results in passive water reabsorption along the osmotic gradient . in heart failure , avp secretion occurs despite a normal or even low plasma osmolality ( non - osmotic avp release)24 ) . arterial underfilling in heart failure contributes to the breakdown of baroreceptor - mediated suppression of avp . in addition , angiotensin ii stimulates the release of avp by the stimulation of the thirst center of the brain3 , 12 ) . thus , the dysregulation of avp plays an important role in the development of hypoosmolar hyponatremia in patients with heart failure . in the kidney , aqp water channels allow the movement of water across the tubular epithelium . aqp1 is abundant in the proximal tubule and descending thin limb and is essential for urinary concentration25 ) . aqp2 is exclusively expressed in the principal cells of the connecting tubule and collecting duct26 ) . it is regulated in the short - term and long - term by the avp / cyclic adenosine monophosphate ( camp ) pathway to increase osmotic water reabsorption27 , 28 ) . aqp3 is present in the basolateral membranes of collecting duct principal cells and represents exit pathways of water reabsorbed via aqp2 in the apical membranes29 ) . in experimental heart failure , nielsen et al . reported increased expression and targeting of aqp2 in association with hyponatremia in experimental heart failure30 ) . xu et al . also demonstrated up - regulation of aqp2 in chronic heart failure rats31 ) . in this study , the expression of aqp2 massenger rna and protein was increased in associated to increased plasma avp levels in heart failure rats . v2 receptor antagonist treatment induced a significant diuresis , decrease in urinary osmolality and increase in plasma osmolality in heart failure rats . up regulation of aqp2 in heart failure is inhibited by the treatment of v2 receptor antagonist . moreover , it was demonstrated that v2 receptor antagonism decreases urinary aqp2 excretion in patients with chronic heart failure32 ) . these results suggest that upregulation of vasopressin and aqp2 plays an important role in the development of water retention and hyponatremia in heart failure . the renal sodium transporters play a critical role in the sodium reabsorption and regulation of extracellular fluid volume . the renal tubular sodium reabsorption is basically linked to the activity of na , k - atpase that is heavily expressed in the basolateral membrane throughout the nephron segments33 ) . the proximal tubule reabsorbs approximately two - thirds of the filtered sodium load . in this segment , type 3 na / h exchanger ( nhe3 ) is mainly responsible for apical sodium reabsorption34 ) . the bumetanide - sensitive na / k/2cl cotransporter ( nkcc2 ) is localized at the apical membrane of the thick ascending limb and mediates the apical nacl transport in this water impermeable segment35 ) . in the distal convoluted tubule , the thiazide - sensitive na / cl cotransporter ( ncc ) is involved in the apical movement of sodium36 ) . on the other hand , epithelial sodium channel ( enac ) in addition , heart failure rats had increased basal and avp stimulated camp accumulation in the thick ascending limb , which was abolished by losartan treatment38 ) . these results may suggest that up - regulation of nkcc2 in heart failure rats plays a role in the increased sodium reabsorption in the thick ascending limb . the nkcc2 expression may be regulated by an interaction between v2 receptor and angiotensin ii receptor . in addition , it was demonstrated that the expressions of aqp2 , nhe3 , nkcc2 and -enac were increased in heart failure rats , which were reversed or prevented by candersartan treatment39 ) . these findings suggest that angiotensin ii and the dysregulation of aqp2 and sodium transporters plays an important role in the pathogenesis of renal sodium and water retention in heart failure . in heart failure , activation of sns , raas , resistance to nps and non - osmotic vasopressin release stimulate the renal tubular reabsorption of sodium and water . dysregulation of aqp2 and sodium transporters also play an important role in the pathogenesis of renal sodium and water retention .
heart failure is the pathophysiological state characterized by ventricular dysfunction and associated clinical symptoms . decreased cardiac output or peripheral vascular resistance lead to arterial underfilling . 
 that is an important signal which triggers multiple neurohormonal systems to maintain adequate arterial pressure and peripheral perfusion of the vital organs . 
 the kidney is the principal organ affected when cardiac output declines . 
 alterations of hemodynamics and neurohormonal systems in heart failure result in renal sodium and water retention . 
 activation of sympathetic nervous system , renin - angiotensin - aldosterone system and non - osmotic vasopressin release stimulate the renal tubular reabsorption of sodium and water . 
 dysregulation of aquaporin-2 and sodium transporters also play an important role in the pathogenesis of renal sodium and water retention .