Altered regulation of renal nitric oxide, atrial natriuretic peptide and cyclooxygenase systems in aldosterone escape in rats.
The present study was aimed to determine whether there is an altered role of local nitric oxide (NO), atrial natriuretic peptide (ANP) and cyclooxygenase (COX) systems in the kidney in association with the aldosterone escape. Male Sprague-Dawley rats were used. Aldosterone (200 microg/day) was infused through entire time course. The control group was kept on a low sodium diet (0.02 mEq/day), and the experimental group was supplied with a higher sodium diet (2. /day). Four days after beginning the regimen, the kidneys were taken. The protein expression of NO synthase (NOS) and COX isoforms was determined by semiquantitative immunoblotting. The mRNA expression of components of ANP system was determined by real-time polymerase chain reaction. The activities of soluble and particulate guanylyl cyclases were determined by the amount of cGMP generated in responses to sodium nitroprusside and ANP, respectively. There developed aldosterone escape in the experimental group. Accordingly, the renal content and the urinary excretion of NO increased. The expression of nNOS was increased in the inner medulla. Neither the expression of eNOS nor that of iNOS was changed. The expression and the catalytic activity of soluble guanylyl cyclase remained unaltered. The mRNA expression of ANP was increased. Neither the expression of NPR-A or NPR-C nor the activity of particulate guanylyl cyclase was altered in the papilla. The protein expression of COX-2 was increased in the inner medulla, while that of COX-1 remained unchanged. In conclusion, the upregulation of nNOS, ANP, and COX-2 may be causally related with the aldosterone escape.
Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea.
Eun Hui
EH
Bae
Hyun Ji
HJ
Cho
In Jin
IJ
Kim
Soo Yeon
SY
Joo
Ji Hye
JH
Shin
Seong Kwon
SK
Ma
JongUn
J
Lee
Soo Wan
SW
Kim
D000450:Aldosterone / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D009320:Atrial Natriuretic Factor / Q000096:biosynthesis*; D051545:Cyclooxygenase 1 / Q000096:biosynthesis; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D007527:Isoenzymes / Q000096:biosynthesis; D007679:Kidney Medulla / Q000201:enzymology*; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis; D009569:Nitric Oxide / Q000096:biosynthesis*; D052248:Nitric Oxide Synthase Type I / Q000096:biosynthesis*; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation / Q000187:drug effects
D000959:Antihypertensive Agents; D007527:Isoenzymes; D008565:Membrane Proteins; D009599:Nitroprusside; D009569:Nitric Oxide; D000450:Aldosterone; D009320:Atrial Natriuretic Factor; D052248:Nitric Oxide Synthase Type I; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496513:Ptgs1 protein, rat; C489691:Ptgs2 protein, rat