Expression of Atrial and Extra-atrial ANP mRNA in Rats with Chronic Renal Failure

Lee, Won Kee; Park, Won Kyun; Hong, Young Su; Song, Dae Kyu; Bae, Jae Hoon

Abstract

Chronic renal failure(CRF) may lead to fluid retention and electrolyte imbalance, and consequently increases the extracellular volume and blood pressure. These changes can trigger secretion and synthesis of atrial natriuretic peptide(ANP) as a compensatory regulator for increases in the glomerular filtration rate and excretion of water and sodium due to the reduced number of functional nephrons. ANP may exert important regulatory role on body fluid balance and blood pressure in CRF. We assessed changes in gene expression of atrial and extra-atrial ANP associated with progression of renal failure in subtotal nephrectomized rats. Adult male Sprague-Dawley rats were divided into sham and CRF rats. CRF rats were induced by 5/6 subtotal nephrectomy. We determined the plasma ANP level using by radioimmunoassay and the ANP mRNA from the right atrium, left ventricle, hypothalamus and kidney were measured by reverse transcription-polymerase chain reaction with 32P- dCTP at 8 wk in sham, and at 8 and 12 wk in CRF rats. Serum urea nitrogen(SUN) was also checked as an indicator of impaired renal function. SUN was significantly increased in CRF rats and the level was higher at CRF 12 wk rat than CRF 8 wk rat. Plasma concentration of ANP also increased in CRF rats compared with sham rat, but was not statistically significant. Altered patterns of ANP mRNA expression were different in each tissue. Right atrial and renal ANP mRNA expressions were slightly increased in CRF rats. Left ventricular ANP mRNA was significantly increased in CRF 8 wk rat compared with sham rat and maintained high at CRF 12 wk rat. However hypothalamic ANP mRNA expressions at CRF rats were decreased and the expression in CRF 12 wk was significantly lower than that at CRF 8 wk. SUN showed positive correlations with expression in left ventricular and renal ANP mRNA, but had a significant negative relationship with hypothalamic ANP mRNA. Plasma ANP concentration was positively correlated with the ANP mRNA expressions in both right atrium and kidney. The present study demonstrated that ANP mRNA in the right atrium, left ventricle, kidney and hypothalamus were differentially expressed upon CRF. This suggests that roles of the local ANP in these tissues are regulated by different mechanisms to compensate the fluid and electrolyte imbalance in rats with experimental chronic renal failure.