title: Indomethacin decreases particulate guanylyl cyclase activity in rat kidney.
abstract: 1. Effects of non-steroidal anti-inflammatory drugs on the local atrial natriuretic peptide (ANP) and nitric oxide (NO) systems in the kidney were investigated. 2. Male Sprague-Dawley rats were treated with indomethacin (5 mg/kg, every 12 h, i.p.) for 2 days. The expression of ANP and natriuretic peptide receptor-A (NPR-A) mRNA was determined in the kidney, as was that of endothelial NO synthase (NOS) proteins. Particulate and soluble guanylyl cyclase activities were determined separately. 3. Following treatment with indomethacin, urinary sodium excretion decreased significantly. Although the renal expression of ANP was not changed significantly, that of NPR-A decreased significantly. The expression of NOS increased significantly. Particulate guanylyl cyclase activity was decreased, whereas the activity of soluble guanylyl cyclase was increased. The catalytic activity of Na(+)/K(+)-ATPase was increased, with no significant changes in its expression. The expression of the type 3 Na/H exchanger and Na-K-2CL cotransporters increased significantly. 4. The indomethacin-induced decrease in urinary sodium excretion may be attributed, at least in part, to decreased activity of the local ANP/cGMP system. The increased activity of the NO/cGMP system may be a compensatory response to the diminished activity of the prostaglandin system.
authors.affiliation: Department of Physiology, Chonnam National University Medical School, Gwangju, Korea. julee@jnu.ac.kr
authors.forename: JongUn
authors.initials: J
authors.lastname: Lee
authors.forename: Soo Wan
authors.initials: SW
authors.lastname: Kim
authors.forename: Tack-Kyoon
authors.initials: TK
authors.lastname: Jung
authors.forename: YoonWha
authors.initials: Y
authors.lastname: Oh
authors.forename: Choon Soon
authors.initials: CS
authors.lastname: Park
authors.forename: Seong Kwon
authors.initials: SK
authors.lastname: Ma
authors.forename: Nam Ho
authors.initials: NH
authors.lastname: Kim
authors.forename: Ki Chul
authors.initials: KC
authors.lastname: Choi
mesh_terms: D000818:Animals; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D007213:Indomethacin / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D006162:Guanylate Cyclase; D007213:Indomethacin