Inhibition of cyclooxygenase-2 attenuates urinary prostanoid excretion without affecting renal renin expression

• Published in: Pflügers Archiv Vol. 442; no. 6; pp. 842 - 847
• Main Authors: Kammerl, M C, Nüsing, R M, Seyberth, H W, Riegger, G A, Kurtz, A, Krämer, B K
• Format: Journal Article
• Language: English
• Published: Germany Springer Nature B.V 01.09.2001
• Subjects: 6-Ketoprostaglandin F1 alpha - urine; Angiotensin-Converting Enzyme Inhibitors - pharmacology; Animals; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors - pharmacology; Diet, Sodium-Restricted; Dinoprostone - urine; Gene Expression - drug effects; Isoenzymes - antagonists & inhibitors; Isoenzymes - genetics; Kidney Cortex - metabolism; Kidney Medulla - enzymology; Kidneys; Lactones - pharmacology; Male; Membrane Proteins; Prostaglandin-Endoperoxide Synthases - genetics; Prostaglandins - urine; Ramipril - pharmacology; Rats; Rats, Sprague-Dawley; Renin - blood; Renin - genetics; Renin - metabolism; Rodents; Sulfones
• ISSN: 0031-6768; 1432-2013
• DOI: 10.1007/s004240100616

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.