Karger, Christian and Machura, Katharina and Schneider, Andre and Hugo, Christian and Todorov, Vladimir T. and Kurtz, Armin (2018) COX-2-derived PGE(2) triggers hyperplastic renin expression and hyperreninemia in aldosterone synthase-deficient mice. PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 470 (7). pp. 1127-1137. ISSN 0031-6768, 1432-2013
Full text not available from this repository. (Request a copy)Abstract
Pharmacological inhibition or genetic loss of function defects of the renin angiotensin aldosterone system (RAAS) causes compensatory renin cell hyperplasia and hyperreninemia. The triggers for the compensatory stimulation of renin synthesis and secretion in this situation may be multimodal. Since cyclooxygenase-2 (COX-2) expression in the macula densa is frequently increased in states of a defective RAAS, we have investigated a potential role of COX-2 and its derived prostaglandins for renin expression and secretion in aldosterone synthase-deficient mice (AS(-/-)) as a model for a genetic defect of the RAAS. In comparison with wild-type mice (WT), AS(-/-) mice had 9-fold and 30-fold increases of renin mRNA and of plasma renin concentrations (PRC), respectively. Renin immunoreactivity in the kidney cortex of AS(-/-) mice was 10-fold higher than in WT. Macula densa COX-2 expression was 5-fold increased in AS(-/-) kidneys relative to WT kidneys. Treatment of AS(-/-) mice with the COX-2 inhibitor SC-236 for 1 week lowered both renal renin mRNA and PRC by 70%. Hyperplastic renin cells in AS(-/-) kidneys were found to express the prostaglandin E-2 receptors EP2 and EP4. Global deletion of EP2 receptors did not alter renin mRNA nor PRC values in AS(-/-) mice. Renin cell-specific inducible deletion of the EP4 receptor lowered renin mRNA and PRC by 25% in AS(-/-) mice. Renin cell-specific inducible deletion of the EP4 receptor in combination with global deletion of the EP2 receptor lowered renin mRNA and PRC by 70-75% in AS(-/-) mice. Lineage tracing of renin-expressing cells revealed that deletion of EP2 and EP4 leads to a preferential downregulation of perivascular renin expression. Our findings suggest that increased macula densa COX-2 activity in AS(-/-) mice triggers perivascular renin expression and secretion via prostaglandin E-2.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | SMOOTH-MUSCLE CELLS; ANGIOTENSIN SYSTEM; PROSTAGLANDIN E-2; MACULA DENSA; CYCLOOXYGENASE-2 EXPRESSION; JUXTAGLOMERULAR CELLS; BLOOD-PRESSURE; EP4 RECEPTOR; RENOVASCULAR HYPERTENSION; PROSTANOID RECEPTORS; Renin cell hyperplasia; Juxtaglomerular cell; Renin; Prostaglandin |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Armin Kurtz |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 02 Mar 2020 09:29 |
| Last Modified: | 02 Mar 2020 09:29 |
| URI: | https://pred.uni-regensburg.de/id/eprint/14356 |
Actions (login required)
 |
View Item |
