Changes of mRNA and Plasma Levels of Atrial Natriuretic Peptide in Subtotal Nephrectomized Rats after High Salt Intake

Kang, Moon Gyoo; Park, Won Kyun; Hong, Young Su; Song, Dae Kyu; Bae, Jae Hoon

Abstract

High salt intake produces volume expansion and electrolyte imbalance in chronic renal failure and modifies the synthesis and secretion of atrial natriuretic peptide(ANP) to compensate the abnormalities in fluid and sodium handling. This study was performed to investigate the effect of high salt intake on modulation of cardiac and noncardiac ANP mRNA as well as plasma ANP levels in 5/6 subtotal nephrectomized (NPX) rats as a model of chronic renal failure. Adult male Sprague-Dawley rats were divided into sham and NPX rats. NPX rats were induced by 2/3 pole ligation and contralateral nephrectomy. Sham and NPX rats had access to normal chow with tap water for 8 weeks or normal chow with 0.45% NaCl solution(HS) for last 2 weeks. Plasma ANP levels were measured by radioimmunoassay. ANP mRNA from the right atrium, left ventricle, hypothalamus and kidney were analyzed by RT-PCR with 32P-dCTP at 8 weeks after surgical operation in both sham and NPX rats. Blood urea nitrogen(BUN) was measured to evaluate impaired renal function. Body weight, daily water intake, hemoglobin, red blood cell, hematocrit, arterial pressure and heart rate were also monitored. Arterial pressure in NPX+HS rat was significantly increased. Both percent increase of body weight and hematologic findings were decreased in NPX rats. Daily water intake was increased in NPX rats, especially in NPX+HS rat. BUN also increased in NPX rats. Plasma ANP concentration was significantly increased in sham+HS rat, but other significant increases were not shown in NPX rats. The levels of right atrial ANP mRNA represented the increasing trend like as plasma ANP. Left ventricular ANP mRNA was increased in sham+HS rat, while the level in NPX+HS rat was decreased comparing with that of sham+HS rat. Hypothalamic ANP mRNA was decreased in NPX+HS rat. In the kidney, the level of ANP mRNA in sham+HS rat was increased comparing with sham rat, but ANP synthesis in NPX+HS rat was significantly lower than in sham, sham+HS and in NPX rats. These findings represent that the high salt intake in NPX rat does not alter the plasma levels and cardiac synthesis of ANP but suppresses the renal ANP mRNA. The diminished renal ANP synthesis may attenuate the regulatory role of ANP system in the kidney and result in volume expansion and hypertension.