| Item type: | Article | ||||
|---|---|---|---|---|---|
| Journal or Publication Title: | Pflügers Archiv - European Journal of Physiology | ||||
| Publisher: | Springer | ||||
| Place of Publication: | NEW YORK | ||||
| Volume: | 470 | ||||
| Number of Issue or Book Chapter: | 7 | ||||
| Page Range: | pp. 1127-1137 | ||||
| Date: | 2018 | ||||
| Institutions: | Biology, Preclinical Medicine > Institut für Physiologie Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Armin Kurtz | ||||
| Identification Number: |
| ||||
| 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 | ||||
| Dewey Decimal Classification: | 500 Science > 570 Life sciences | ||||
| Status: | Published | ||||
| Refereed: | Yes, this version has been refereed | ||||
| Created at the University of Regensburg: | Yes | ||||
| Item ID: | 47063 |
Web of ScienceAbstract
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 ...
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.
Metadata last modified: 28 Jul 2021 17:13
Altmetric