Atrial peptides and the renal response to hypervolemia in nephrotic rats

Abstract

Immunoreactive atrial natriuretic peptide (iANP) levels in plasma of edematous rats with an experimental nephrotic syndrome produced by the injection of puromycin aminonucleoside (PAN) were not different from those in untreated rats. To test the ability of nephrotic rats to secrete iANP in response to a volume stress, the rats were subjected to 20% expansion of their estimated blood volumes using blood from donor rats. PAN-treated rats had very small natriuretic and diuretic responses compared with untreated rats; however, there was no difference in the secretory response of iANP, which increased approximately threefold in each group. There were highly significant correlations between changes in plasma iANP and changes in right atrial pressure in both normal and nephrotic rats. Nephrotic rats that were infused with synthetic ANP showed only a very small natriuretic and diuretic response compared with normal rats, and no change in glomerular filtration rate. The hypotensive response was still present, however. Urine concentration in nephrotic rats was much lower than in controls and was not increased by exogenous arginine vasopressin. It is concluded that the absence of a normal natriuretic and diuretic response to hypervolemia in PAN-treated rats is not caused by a failure to secrete ANP but might be a result of an intrarenal defect that makes their kidneys unresponsive.

Restoration of Renal Responsiveness to Atrial Natriuretic Peptide in Experimental Nephrotic Syndrome by Albumin Infusion

“…The blunt natriuretic/diuretic response to ANP in rats with experimentally induced NS is a well-established finding that we [14] and other investigators [6,7,9,10,11,12,13,14,15,16,17,18] have previously documented. The inability of the kidney to normally increase sodium excretion in response to ANP, which is also observed in other edema-forming states such as congestive heart failure [19,20,21,22] and liver cirrhosis [23], has been postulated as an important mechanism leading to salt retention and edema formation [9,11,13,24].…”

“…The natriuretic/diuretic response to either saline load [4,5,6,7] or exogenous infusion of atrial natriuretic peptide (ANP), an important regulator of water and Na + balance [8], is markedly attenuated in rats with ADR-induced NS [8,9,10,11,12,13,14,15]. It has been suggested that the diminished renal responsiveness to ANP may contribute to the pathogenesis of salt retention and edema formation in NS [13,16].…”

Glomerular abundance of nephrin and podocin in experimental nephrotic syndrome: different effects of antiproteinuric therapies

“…Nephrin loss is an indication of proteinuria in NS and the antiproteinuric effects of ACE inhibitors, vasopeptidase inhibitors, and mycophenolate mofetil attenuate this reduction. Not all the drugs which restore podocin reduce urinary protein in NS.adriamycin; proteinuria ADRIAMYCIN (ADR)-induced nephrotic syndrome (NS) in the rat is characterized by massive proteinuria, hypoalbuminemia, dyslipidemia, hypercoagulability, edema, and ascites formation (5,16,25,26). The common denominator of this experimental nephropathy, which mimics minimal change disease and various primary and secondary kidney diseases such as diabetic nephropathy, systemic lupus erythematosus and others, is glomerular dysfunction resulting in a massive proteinuria (8).…”

“…dyslipidemia, hypercoagulability, edema, and ascites formation (5,16,25,26). The common denominator of this experimental nephropathy, which mimics minimal change disease and various primary and secondary kidney diseases such as diabetic nephropathy, systemic lupus erythematosus and others, is glomerular dysfunction resulting in a massive proteinuria (8).…”

Severe Proteinuria without Impairment of Sodium and Volume Excretion after Puromycin Aminonucleoside Administration in Rats

“…A rat model of nephrotic syndrome can be induced by aminonucleosides of puromycin [1][2][3][4][5] or adriamycin [6][7][8]. Both compounds cause glomer ular alterations resulting in albuminuria [1,4,6], and impaired sodium and volume ex cretion under basal conditions [2,3,5,8] as well as after blood volume expansion or after infusion of atrial natriuretic peptide (ANP) [5,7,8], The sodium and volume retention in nephrotic syndrome seems to be confined to the distal tubule or the medullary collect ing duct system [3,9,10], Recently, several studies have suggested that the sodium and volume retention in nephrotic syndrome may not simply be due to a compensatory humoral mechanism as a consequence of hypovolemia resulting from hypoalbuminemia, but may be the result of a separate intrinsic tubular lesion of the ne phrotic kidney: the administration of pred nisolone to patients suffering from nephrotic syndrome induces diuresis and natriuresis without prior elevation of blood volume or plasma albumin concentration [11], The se lective perfusion of one kidney with puromy cin aminonucleoside (PAN) [ I ] induces uni lateral proteinuria and sodium retention, whereas the contralateral kidney compen sates by increasing sodium excretion [2], Fi nally, unilateral sodium retention after se lective perfusion with PAN can occur with out hypoproteinemia and edema [3], If the sodium retention after aminonu cleoside administration is due to a specific tubular lesion rather than a reaction to ex cessive protein loss, the question rises whether these two effects can be distin guished with regard to their dose depen dence. A fully developed nephrotic syn drome can be seen after a single administra tion of 150 mg/kg PAN in rats [5], Therefore, we decided to investigate the effects of PAN at 2/3 of this dose on basal sodium and fluid excretion as well as on the response to blood volume expansion and ANP infusion.…”