Inhibition of cyclooxygenase-2 attenuates urinary prostanoid excretion without affecting renal renin expression.
This study aimed to assess the impact of cyclooxygenase-2 (COX-2) on the secretion and expression of renin in the kidney cortex. For this purpose renocortical COX-2 expression was moderately stimulated by a low-salt diet or strongly stimulated (increase in mRNA about fivefold) by the combination of a low-salt diet and the angiotensin-I-converting enzyme inhibitor ramipril in male Sprague-Dawley rats. None of these manoeuvres changed medullary COX-2 expression or cortical or medullary COX-1 expression. Treatment with low salt plus ramipril but not with low salt alone led to a three- to fourfold increase of the urinary output of all major prostanoids. The selective COX-2 inhibitor rofecoxib (10 mg/kg per day) markedly lowered basal urinary prostanoid excretion and blunted the stimulation of prostanoid excretion during treatment with low salt plus ramipril. The stimulation of renin secretion by the low-salt diet but not by low salt plus ramipril was attenuated by rofecoxib. The low-salt diet led to a moderate increase of renin gene expression, and additional treatment with ramipril caused a 15-fold increase of renin mRNA. However, no effect of rofecoxib on renin gene expression was observed in any group. These findings suggest that stimulation of COX-2 in the renal cortex leads to the increased formation of all major prostanoids. COX-2-derived prostanoids may play a role in the regulation of renin secretion but not in renin gene expression during the intake of a low-salt diet. However, no major relevance of COX-2-derived prostanoids to renin secretion or renin gene expression during ramipril treatment or a combination of ramipril and a low-salt diet was found.
Kammerl
M C
MC
Institut für Physiologie 1, University of Regensburg, Germany. martin.kammerl@klinik.uni-regensburg.de
Nüsing
R M
RM
Seyberth
H W
HW
Riegger
G A
GA
Kurtz
A
A
Krämer
B K
BK
D015121:6-Ketoprostaglandin F1 alpha / Q000652:urine; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004039:Diet, Sodium-Restricted; D015232:Dinoprostone / Q000652:urine; D015870:Gene Expression / Q000187:drug effects*; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000235:genetics; D007672:Kidney Cortex / Q000378:metabolism*; D007679:Kidney Medulla / Q000201:enzymology; D007783:Lactones / Q000494:pharmacology; D008297:Male; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics; D011453:Prostaglandins / Q000652:urine*; D017257:Ramipril / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D013450:Sulfones
D000806:Angiotensin-Converting Enzyme Inhibitors; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D007783:Lactones; D008565:Membrane Proteins; D011453:Prostaglandins; D013450:Sulfones; C116926:rofecoxib; D015121:6-Ketoprostaglandin F1 alpha; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496513:Ptgs1 protein, rat; D012083:Renin; D015232:Dinoprostone; D017257:Ramipril