title: Angiotensin II stimulates renin in inner medullary collecting duct cells via protein kinase C and independent of epithelial sodium channel and mineralocorticoid receptor activity.
abstract: Collecting duct (CD) renin is stimulated by angiotensin (Ang) II, providing a pathway for Ang I generation and further conversion to Ang II. Ang II stimulates the epithelial sodium channel via the Ang II type 1 receptor and increases mineralocorticoid receptor activity attributed to increased aldosterone release. Our objective was to determine whether CD renin augmentation is mediated directly by Ang II type 1 receptor or via the epithelial sodium channel and mineralocorticoid receptor. In vivo studies examined the effects of epithelial sodium channel blockade (amiloride; 5 mg/kg per day) on CD renin expression and urinary renin content in Ang II-infused rats (80 ng/min, 2 weeks). Ang II infusion increased systolic blood pressure, medullary renin mRNA, urinary renin content, and intrarenal Ang II levels. Amiloride cotreatment did not alter these responses despite a reduction in the rate of progression of systolic blood pressure. In primary cultures of inner medullary CD cells, renin mRNA and (pro)renin protein levels increased with Ang II (100 nmol/L), and candesartan (Ang II type 1 receptor antagonist) prevented this effect. Aldosterone (10(-10) to 10(-7) mol/L) with or without amiloride did not modify the upregulation of renin mRNA in Ang II-treated cells. However, inhibition of protein kinase C with calphostin C prevented the Ang II-mediated increases in renin mRNA and (pro)renin protein levels. Furthermore, protein kinase C activation with phorbol 12-myristate 13-acetate increased renin expression to the same extent as Ang II. These data indicate that an Ang II type 1 receptor-mediated increase in CD renin is induced directly by Ang II via the protein kinase C pathway and that this regulation is independent of mineralocorticoid receptor activation or epithelial sodium channel activity.
authors.affiliation: Department of Physiology and Tulane Renal Hypertension and Renal Center , Tulane University, School of Medicine, New Orleans, LA 70112, USa.
authors.forename: Alexis A
authors.initials: AA
authors.lastname: Gonzalez
authors.forename: Liu
authors.initials: L
authors.lastname: Liu
authors.forename: Lucienne S
authors.initials: LS
authors.lastname: Lara
authors.forename: Dale M
authors.initials: DM
authors.lastname: Seth
authors.forename: L Gabriel
authors.initials: LG
authors.lastname: Navar
authors.forename: Minolfa C
authors.initials: MC
authors.lastname: Prieto
mesh_terms: D000704:Analysis of Variance; D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D053503:Epithelial Sodium Channels / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism; D007679:Kidney Medulla / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018161:Receptors, Mineralocorticoid / Q000378:metabolism*; D012083:Renin / Q000378:metabolism*; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
chemical_list: D053503:Epithelial Sodium Channels; D018161:Receptors, Mineralocorticoid; D000804:Angiotensin II; D011493:Protein Kinase C; D012083:Renin