General inhibition of renocortical cyclooxygenase-2 expression by the renin-angiotensin system.
Because across-the-board data indicate that renin and cyclooxygenase-2 (COX-2) expression in the kidney cortex are regulated in parallel and because ANG II can inhibit COX-2 expression, the purpose of our study was to characterize a potential general inhibitory feedback of the renin-angiotensin system on renocortical COX-2 expression in vivo. Rats were fed a high-, normal-, or low-salt diet or were chronically infused with furosemide (60 mg. kg(-1). day(-1)) or the left renal artery was clipped, and the animals were treated in addition to or without the angiotensin-converting enzyme inhibitor ramipril (10 mg. kg(-1). day(-1)). A high-salt diet reduced expression of COX-2, whereas a low-salt diet, furosemide infusion, and renal artery stenosis stimulated COX-2 expression. Additional angiotensin-converting enzyme inhibition led to further increases in renocortical COX-2 expression by 62, 136, 300, 50, and 70% for a high-, normal-, and low-salt diet, furosemide infusion, and renal artery stenosis, respectively. Thus our data suggest a general inhibitory effect of the renin-angiotensin system on renocortical COX-2 expression.
Castrop
Hayo
H
Institut für Physiologie und Pharmakologie der Universität Regensburg, D-93040 Regensburg, Germany.
Klar
Jurgen
J
Wagner
Charlotte
C
Hocherl
Klaus
K
Kurtz
Armin
A
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D025461:Feedback, Physiological / Q000187:drug effects / Q000502:physiology*; D005665:Furosemide / Q000494:pharmacology; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D007672:Kidney Cortex / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012078:Renal Artery Obstruction / Q000378:metabolism; D012083:Renin / Q000235:genetics / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000502:physiology*; D012982:Sodium, Dietary / Q000494:pharmacology
D000806:Angiotensin-Converting Enzyme Inhibitors; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D012333:RNA, Messenger; D012982:Sodium, Dietary; D005665:Furosemide; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D012083:Renin