Abstract: SA-PO1092

Metformin Treatment Downregulates Intrarenal Renin-Angiotensin System in Angiotensin II Infused Mice

Session Information

Category: Hypertension

  • 1102 Hypertension: Basic and Experimental - Renal Causes and Consequences

Authors

  • Alzamora, Rodrigo, Universidad de Chile, Santiago, Chile
  • Barrientos, Victor Manuel, University of Chile, Santiago, Chile
  • Leon, Pablo Andres, Universidad de Chile, Santiago, Chile
  • Michea, Luis F., Facultad de Medicina, U de Chile, Santiago, Chile
Background

Activation of an intrarenal renin-angiotensin system (irRAS) is a characteristic of angiotensin II (AngII) induced hypertension. The irRAS contributes to the development and progression of hypertension, by increasing tubular sodium reabsorption, and promotes kidney tissue damage. Recent data have suggested an antihypertensive effect of metformin in several animal models of hypertension. Metformin activates the AMP-activated protein kinase (AMPK), which has been reported to downregulates the activity of renal sodium channels and transporters. We evaluated the effect of metformin treatment on blood pressure (BP) and the expression of components of the irRAS.

Methods

Changes in BP and expressions of angiotensinogen (AGT), renin, AngII type-1 receptor (AT1R) and angiotensin converting enzyme (ACE) were measured in kidney tissue from AngII-infused C57/BL6 mice with or without metformin treatment.

Results

Metformin-treatment prevented the AngII-induced increase in SBP compared to control mice (AngII 153±6 vs. AngII+Met 105±5 mmHg, P>0.05, n=4) and decreased renal expressions of renin, ACE and AT1R but did not modified the induction of AGT. As compared to control mice, phosphorylation of AMPK (T172) was decreased in AngII-infused mice (52% reduction, P>0.05, n=4) but restored by metformin-treatment. Additionally, metformin-treatment prevented the induction of Na+-H+-exchanger-3 (NHE3) expression in kidney cortex from Ang-II infused mice. In contrast, metformin-treatment had no effect on BP, irRAS components and NHE3 expression in control mice.

Conclusion

Metformin has protective effects, by preventing AngII-induced increase in BP, the induction of irRAS and the upregulation of NHE3 caused by AngII infusion.
Supported by FONDECYT 1151423 and 1130550, The Millennium Nucleus of Ion Channels-Associated Diseases (MiNICAD). The Millennium Institute on Immunology and Immunotherapy (MIII) P09/016-F (ICM).

Funding

  • Government Support - Non-U.S.