title: Renocortical expression of renin and of cyclooxygenase-2 in response to angiotensin II AT1 receptor blockade is closely coordinated but not causally linked.
abstract: Based on recent evidence that renin gene and cyclooxygenase-2 (COX-2) expression in the rat kidney cortex increase in parallel under a variety of conditions, this study aimed to characterize the causal linkage between COX-2 and renin expression. Therefore, we semi-quantitated renocortical renin and COX-2 gene expression when the renin-angiotensin system (RAS) was inhibited by the angiotensin II (Ang II) AT1 receptor antagonist candesartan (15 mg/kg per day) and when COX-2 activity was blocked by celecoxib (20 mg/kg twice a day) in three rat strains (Sprague-Dawley, WKY and SHR) at ages of 5, 9 and 15 weeks. We observed that candesartan increased renin mRNA in all rats at all ages, the amplitude of stimulation being inversely related to age. Candesartan increased COX-2 mRNA in all three strains at 5 weeks, and in SD and WKY rats also at 9 weeks. In 9-week-old SHR and in 15-week-old rats of all three strains candesartan did not influence COX-2 mRNA levels. For all rat strains, strain-specific strong linear correlations existed between renocortical COX-2 and renin mRNA levels, both with and without candesartan treatment. The additional feeding of candesartan-treated rats with celecoxib did not change renin mRNA or COX-2 mRNA levels, whilst the renal excretion of sodium and renal cortical prostaglandin E2 concentration decreased by 26% and 60%, respectively. In summary, these findings, obtained when the renin system was activated by AT1 receptor blockade, indicate that Ang II is not required to stimulate COX-2 expression and that COX-2 activity is not required to stimulate renin expression. However, the renocortical expression of renin and of COX-2 appear to be highly coordinated under basal conditions and during inhibition of RAS, suggesting the existence of a common denominator for renin and COX-2 expression that remains to be elucidated.
authors.affiliation: Institut für Pharmakologie der Universität Regensburg, Germany. klaus.hoecherl@chemie.uni-regensburg.de
authors.forename: K
authors.initials: K
authors.lastname: Höcherl
authors.forename: K
authors.initials: K
authors.lastname: Wolf
authors.forename: H
authors.initials: H
authors.lastname: Castrop
authors.forename: K P
authors.initials: KP
authors.lastname: Ittner
authors.forename: M
authors.initials: M
authors.lastname: Bucher
authors.forename: F
authors.initials: F
authors.lastname: Kees
authors.forename: H F
authors.initials: HF
authors.lastname: Grobecker
authors.forename: A
authors.initials: A
authors.lastname: Kurtz
mesh_terms: D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds; D000068579:Celecoxib; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000235:genetics*; D007672:Kidney Cortex / Q000378:metabolism*; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics*; D011720:Pyrazoles; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1; D012083:Renin / Q000235:genetics*; D013449:Sulfonamides / Q000494:pharmacology; D013777:Tetrazoles / Q000494:pharmacology
chemical_list: D057911:Angiotensin Receptor Antagonists; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D011720:Pyrazoles; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D013449:Sulfonamides; D013777:Tetrazoles; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D012083:Renin; D000068579:Celecoxib; D015232:Dinoprostone; C081643:candesartan