Renocortical expression of renin and of cyclooxygenase-2 in response to angiotensin 11 AT(1) receptor blockade is closely coordinated but not causally linked

Hoecherl, Klaus and Wolf, Konrad and Castrop, Hayo and Ittner, Karl Peter and Bucher, Michael and Kees, Frieder and Grobecker, Horst F. and Kurtz, Armin (2001) Renocortical expression of renin and of cyclooxygenase-2 in response to angiotensin 11 AT(1) receptor blockade is closely coordinated but not causally linked. PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 442 (6). pp. 821-827. ISSN 0031-6768, 1432-2013

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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 SID and WKY rats also at 9 weeks. In 9-week-old SUR 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 E-2 concentration decreased by 26% and 60%, respectively. In summary, these findings, obtained when the renin system was activated by AT(1) 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.

Item Type: Article
Uncontrolled Keywords: NITRIC-OXIDE-SYNTHASE; MESSENGER-RNA; RENOVASCULAR HYPERTENSION; GENE-EXPRESSION; MACULA DENSA; RAT-KIDNEY; INHIBITION; SPIRONOLACTONE; IDENTIFICATION; STIMULATION; angiotensin II; cyclooxygenase-2; kidney; prostaglandins; renin; spontaneously hypertensive rats (SHR)
Subjects: 500 Science > 570 Life sciences
600 Technology > 610 Medical sciences Medicine
600 Technology > 615 Pharmacy
Divisions: Medicine > Lehrstuhl für Innere Medizin II
Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Armin Kurtz
Chemistry and Pharmacy > Institute of Pharmacy > Alumni or Retired Professors > Prof. Frieder Kees
Depositing User: Dr. Gernot Deinzer
Date Deposited: 13 Dec 2021 09:33
Last Modified: 13 Dec 2021 09:33
URI: https://pred.uni-regensburg.de/id/eprint/41166

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