We examined renal sodium handling in rats with Heymann nephritis (HEN), an immunologically mediated model of nephrotic syndrome. Rats were studied 9-14 days following ip injection of anti-Fx1A antiserum. We previously demonstrated that HEN had a blunted volume expansion natriuresis (2 % body weight isotonic saline infused over 5 min), excreting sodium at only half the rate of normal controls (CTL) despite similar increase in plasma atrial natriuretic peptide (ANP) concentration. Urinary excretion of cGMP was also reduced by half in HEN compared to CTL. We next compared cGMP accumulation by isolated glomeruli and inner medullary collecting duct (IMCD) cells in response to increasing concentration of ANP, and RNP (also called urodilatin). Results (fmol/mg prot/10 min) are means +/- SEM : [GRAPHICS] significantly less than CTL; p < 0.05. Basal accumulation of cGMP was not different among the groups, HEN rats hd reduced cGMP accumulation in response to ANP, and RNP. In binding studies using I-125-ANP, no difference in either density or affinity was found between CTL and HEN rats. Thus, there is a renal resistance to ANP in rats with HEN, which can be extended to other agents acting through the cGMP pathway. This resistance is not due to impaired binding of ANP, but to impaired accumulation of cGMP in responsive tissues, reflecting perharps increased cGMP catabolism by phosphodiesterase. Such an observation may account for the altered sodium handling in nephrotic rats.

RATS WITH HEYMANN NEPHRITIS ARE RESISTANT TO THE ACTIONS OF ATRIAL AND RENAL NATRIURETIC PEPTIDES TO INCREASE CGMP ACCUMULATION IN-VITRO

SECHI, Leonardo Alberto;
1994

Abstract

We examined renal sodium handling in rats with Heymann nephritis (HEN), an immunologically mediated model of nephrotic syndrome. Rats were studied 9-14 days following ip injection of anti-Fx1A antiserum. We previously demonstrated that HEN had a blunted volume expansion natriuresis (2 % body weight isotonic saline infused over 5 min), excreting sodium at only half the rate of normal controls (CTL) despite similar increase in plasma atrial natriuretic peptide (ANP) concentration. Urinary excretion of cGMP was also reduced by half in HEN compared to CTL. We next compared cGMP accumulation by isolated glomeruli and inner medullary collecting duct (IMCD) cells in response to increasing concentration of ANP, and RNP (also called urodilatin). Results (fmol/mg prot/10 min) are means +/- SEM : [GRAPHICS] significantly less than CTL; p < 0.05. Basal accumulation of cGMP was not different among the groups, HEN rats hd reduced cGMP accumulation in response to ANP, and RNP. In binding studies using I-125-ANP, no difference in either density or affinity was found between CTL and HEN rats. Thus, there is a renal resistance to ANP in rats with HEN, which can be extended to other agents acting through the cGMP pathway. This resistance is not due to impaired binding of ANP, but to impaired accumulation of cGMP in responsive tissues, reflecting perharps increased cGMP catabolism by phosphodiesterase. Such an observation may account for the altered sodium handling in nephrotic rats.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11390/680189
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