COX-2 activity determines the level of renin expression but is dispensable for acute upregulation of renin expression in rat kidneys.
The role of cyclooxygenase 2 (COX-2) in the control of renin is still a matter of debate, since studies with COX-2-deficient mice or with COX-2 inhibitors produced conflicting findings. Therefore, we studied the effect of the COX-2 inhibitor SC-58236 on the regulation of the renin system in adult rat kidneys. Renocortical tissue levels and urinary excretion of PGE(2) were reduced to 65 and 40% of control values, respectively, after a single gavage of SC-58236 and did not further decrease on prolonged treatment. Plasma renin activity (PRA) and renin mRNA levels began to decrease after 3 days and reached a constant level of approximately 60% of control values after 5 days of treatment. Isoproterenol or left renal artery clipping for 2 days increased PRA and renin mRNA to similar levels in both vehicle- and SC-58236-treated rats after 2 days. Pretreatment with SC-58236 for 5 days, however, reduced the absolute increase in PRA and renin mRNA levels. Notably, the relative increases were not different between vehicle- and SC-58236-treated rats. Similar findings were observed for the stimulation of the renin system by angiotensin II inhibition and low salt intake. These findings indicate that COX-2 inhibition attenuates renin secretion and renin gene expression stimulated by a variety of parameters in proportion to the lowering of basal renin activity, while it does not interfere with the different stimulatory mechanism per se. As a consequence, it appears as if COX-2 activity relevantly determines the set point of the activity of the renin system in rat kidneys.
Matzdorf
Corina
C
Institute für Pharmakologie, Universität Regensburg, Regensburg, Germany.
Kurtz
A
A
Höcherl
Klaus
K
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000097:blood; D004232:Diuretics / Q000494:pharmacology; D005665:Furosemide / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006978:Hypertension, Renovascular / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D007668:Kidney / Q000201:enzymology* / Q000378:metabolism*; D008297:Male; D011453:Prostaglandins / Q000378:metabolism / Q000502:physiology; D011720:Pyrazoles / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000096:biosynthesis* / Q000097:blood; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012964:Sodium / Q000172:deficiency; D013449:Sulfonamides / Q000494:pharmacology; D015854:Up-Regulation / Q000502:physiology; D000096926:Benzenesulfonamides
D000318:Adrenergic beta-Agonists; D047228:Angiotensin II Type 1 Receptor Blockers; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D015232:Dinoprostone; D004232:Diuretics; D005665:Furosemide; D007545:Isoproterenol; D011453:Prostaglandins; D011720:Pyrazoles; D012333:RNA, Messenger; D012083:Renin; D012964:Sodium; D013449:Sulfonamides; C119130:4-(5-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide; D000096926:Benzenesulfonamides