Local renal and vascular natriuretic peptide system in obstructive uropathic rats

The present study was aimed at investigating whether the regulation of the local natriuretic peptide system is altered in the kidney and the vasculature in obstructive uropathy. Male Sprague-Dawley rats were bilaterally obstructed by ligation of the proximal ureters for 48 h. Control rats were treated in the same way, except that no ligature was made. The mRNA expression of the various isoforms of atrial, brain, and C-type natriuretic peptide (ANP, BNP, CNP) and different subtypes of natriuretic peptide receptor-A, -B, and -C (NPR-A, NPR-B, NPR-C) was determined in the kidney and the thoracic aorta by reverse transcription-polymerase chain reaction. The basal and stimulated activities of particulate guanylyl cyclase were also examined. Following the bilateral ureteral obstruction, the expression of ANP, BNP, and CNP was increased in the aorta as well as in the kidney. Contrary to this, the expression of NPR-A, NPR-B, and NPR-C was decreased both in the kidney and the aorta. Accordingly, the guanylyl cyclase activity was significantly decreased in response to natriuretic peptides. ANP relaxed phenylephrine-precontracted aortic rings in a dose-dependent manner, the degree of which was significantly diminished. Our results suggest that the local synthesis of natriuretic peptides is increased in the kidney and in the vasculature in obstructive uropathy.