Prostaglandin E-prostanoid4 receptor mediates angiotensin II-induced (pro)renin receptor expression in the rat renal medulla
Autor: | Yaomin Du, Shu-Feng Zhou, Tianxin Yang, Kexin Peng, Xiaohan Lu, Fei Wang, Aihua Zhang |
---|---|
Rok vydání: | 2014 |
Předmět: |
Agonist
Male medicine.medical_specialty medicine.drug_class Receptors Prostaglandin EP4 Receptor Receptors Cell Surface Plasma renin activity Article Rats Sprague-Dawley Renin-Angiotensin System Downregulation and upregulation Internal medicine Renin–angiotensin system Internal Medicine Renal medulla medicine Animals Prorenin Receptor Receptor Cells Cultured Kidney Medulla Chemistry Angiotensin II Rats medicine.anatomical_structure Endocrinology Receptors Prostaglandin E EP4 Subtype |
Zdroj: | Hypertension (Dallas, Tex. : 1979). 64(2) |
ISSN: | 1524-4563 |
Popis: | Angiotensin II (Ang II) stimulates (pro)renin receptor (PRR) expression in the renal collecting duct, triggering the local renin response in the distal nephron. Our recent study provided evidence for involvement of cyclooxygenase-2–prostaglandin E 2 pathway in Ang II-dependent stimulation of PRR expression in the collecting duct. Here, we tested the role of E-prostanoid (EP) subtypes acting downstream of cyclooxygenase-2 in this phenomenon. In primary rat inner medullary collecting duct cells, Ang II treatment for 12 hours induced a 1.8-fold increase in the full-length PRR protein expression. To assess the contribution of EP receptor, the cell was pretreated with specific EP receptor antagonists: SC-51382 (for EP 1 ), L-798106 (for EP 3 ), L-161982 (for EP 4 ), and ONO-AE3-208 (ONO, a structurally distinct EP 4 antagonist). The upregulation of PRR expression by Ang II was consistently abolished by L-161982 and ONO and partially suppressed by SC-51382 but was unaffected by L-798106. The PRR expression was also significantly elevated by the EP 4 agonist CAY10598 in the absence of Ang II. Sprague-Dawley rats were subsequently infused for 1 or 2 weeks with vehicle, Ang II alone, or in combination with ONO. Ang II infusion induced parallel increases in renal medullary PRR protein and renal medullary and urinary renin activity and total renin content, all of which were blunted by ONO. Both tail cuff plethysmography and telemetry demonstrated attenuation of Ang II hypertension by ONO. Overall, these results have established a crucial role of the EP 4 receptor in mediating the upregulation of renal medullary PRR expression and renin activity during Ang II hypertension. |
Databáze: | OpenAIRE |
Externí odkaz: |