Altered Atrial Natriuretic Peptide System in the Kidney of Bilateral Obstructive Uropathic Rats

Park, Jong Wook; Paek, Yun Woong; Yeum, Chung Ho; Nah, Myong Yun; Kim, Soo Wan

Abstract

BACKGROUND: Although being associated with an elevated plasma atrial natriuretic peptide(ANP), its precise role in the postobstructive diuresis has not been fully understood. Evidence has been provided suggesting that the locally-synthesized ANP in the kidney contributes to the regulation of urinary sodium excretion. The present study was aimed to investigate whether an altered regulation of local ANP system is involved in the postobstructive diuresis.
METHODS
Male Sprague-Dawley rats were used. Both proximal ureters were ligated for 48 hours, after which the kidneys were taken without releasing the ligature, being designated as bilateral ureteral obstruction(BUO) group; or the ligature was released and 4 or 24 hr later, urinary data were collected, being designated as BUR-4 or BUR-24, respectively. Sham operated rats were used as control. Plasma ANP levels were determined by radioimmunoassay. The expression of ANP and natriuretic peptide receptor(NPR)-A mRNAs was determined by reverse transcription-polymerase chain reaction(RT-PCR). To further examine whether the altered renal ANP system, if any, was associated with an altered biological effects of guanylyl cyclase, ANP-stimulated cGMP accumulation was determined in membrane preparations of the glomeruli and papillae by radioimmunoassay.
RESULTS
The plasma ANP level was increased in BUO group compared with that in the control(260.5+/-32.5 vs. 133.3+/-23.5pg/mL, p<0.05), decreased in BUR-4 group(3.6+/-0.5 vs. 143.5+/-42.8pg/mL, p<0.01), while not significantly different in BUR-24 group. In BUR-4. the urinary flow rate increased compared with that in the control(1598+/-370 vs. 215+/-34 microL/hr, p<0.01), along with increases of FENa(11.5+/-4.1 vs. 0.25+/-0.02%, p<0.05) and UNaV (153.7+/-23.7 vs. 36.5+/-9.3microEq/hr, p<0.01). In BUR-24, the urinary parameters were normalized. Renal tissue expression of ANP mRNA was increased in BUO as well as in BUR-4, while not changed in BUR-24. NPR-A mRNA expression was decreased in the kidney of BUO. The ANP-stimulated accumulation of cGMP in the isolated glomeruli and papillae in BUO was significantly reduced. The guanylyl cyclase activities were partly recovered in BUR-4 and completely in BUR-24.
CONCLUSION
An enhanced local activity of ANP in the kidney may be causally related to the postobstructive diuresis.