Bradykinin/B 2 receptor activation regulates renin in M-1 cells via protein kinase C and nitric oxide

• Published in: Physiological reports Vol. 5; no. 7; p. e13211
• Main Authors: Lara, Lucienne S, Bourgeois, Camille R T, El-Dahr, Samir S, Prieto, Minolfa C
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.04.2017
• Subjects: Angiotensin; Animals; Blood pressure; Bradykinin; Bradykinin - analogs & derivatives; Bradykinin - pharmacology; Bradykinin B2 Receptor Antagonists - pharmacology; Cell culture; Cell Line; Collecting duct; Culture media; Cyclic GMP; Gene expression; Homeostasis; Immunoreactivity; Isoquinolines - pharmacology; Kallikrein; Kidney Cortex - cytology; Kidney Cortex - drug effects; Kidney Cortex - metabolism; Kinases; Mice; Naphthalenes - pharmacology; NG-Nitroarginine methyl ester; NG-Nitroarginine Methyl Ester - pharmacology; Nitric oxide; Nitric Oxide - metabolism; Nitric-oxide synthase; Physiology; Protein kinase; Protein kinase A; Protein kinase C; Protein Kinase C - metabolism; Protein Kinase Inhibitors - pharmacology; Proteins; Reabsorption; Receptor mechanisms; Receptor, Bradykinin B2 - metabolism; Renin; Renin - metabolism; Rodents; Sulfonamides - pharmacology; cGMP; prorenin; protein kinase A; distal tubular renin; gene expression
• ISSN: 2051-817X
• DOI: 10.14814/phy2.13211

In the collecting duct (CD), the interactions of renin angiotensin system (RAS) and kallikrein-kinin system (KKS) modulate Na reabsorption, volume homeostasis, and blood pressure. In this study, we used a mouse kidney cortical CD cell line (M-1 cells) to test the hypothesis that in the CD, the activation of bradykinin B receptor (B R) increases renin synthesis and release. Physiological concentrations of bradykinin (BK) treatment of M-1 cells increased renin mRNA and prorenin and renin protein contents in a dose-dependent manner and increased threefold renin content in the cell culture media. These effects were mediated by protein kinase C (PKC) independently of protein kinase A (PKA) because B R antagonism with Icatibant and PKC inhibition with calphostin C, prevented these responses, but PKA inhibition with H89 did not modify the effects elicited by the B R activation. BK-dependent stimulation of renin gene expression in CD cells also involved nitric oxide (NO) pathway because increased cGMP levels and inhibition of NO synthase with L-NAME prevented it. Complementary renin immunohistochemical studies performed in kidneys from mice with conventional B R knockout and conditional B R knockout in the CD, showed marked decreased renin immunoreactivity in CD, regardless of the renin presence in juxtaglomerular cells in the knockout mice. These results indicate that the activation of B R increases renin synthesis and release by the CD cells through PKC stimulation and NO release, which support further the interactions between the RAS and KKS.