Abstract: TH-PO694

High Fat Diet Increases Plasma Soluble Prorenin Receptor (sPRR), Ang II, Systolic Blood Pressure (SBP), and Arterial Stiffness in Type 2 Diabetic (T2D) Male but Not in Female Mice

Session Information

Category: Diabetes

  • 501 Diabetes Mellitus and Obesity: Basic - Experimental

Authors

  • Visniauskas, Bruna, Tulane University School of Medicine, New Orleans, Louisiana, United States
  • Reverte, Virginia, Tulane University School of Medicine, New Orleans, Louisiana, United States
  • Rosales, Carla B, Tulane University School of Medicine, New Orleans, Louisiana, United States
  • Galeas-Pena, Michelle, Tulane University School of Medicine, New Orleans, Louisiana, United States
  • Abshire, Caleb M, Tulane University School of Medicine, New Orleans, Louisiana, United States
  • Lindsey, Sarah, Tulane University School of Medicine, New Orleans, Louisiana, United States
  • Prieto, Minolfa C., Tulane University School of Medicine, New Orleans, Louisiana, United States
Background

Activation of the renin angiotensin system (RAS) leads to complications during T2D; however, whether these outcomes exhibit sex differences remains unknown. Plasma prorenin levels are high in T2D patients and associated to microvascular complications. The sPRR activates prorenin in the extracellular compartments. In this study, we determined if plasma sPRR contributes to sex differences in the RAS and complications in a murine model of high fat diet (HFD)-induced T2D.

Methods

Male and female C57BL/6 mice were subjected to normal diet (NFD; Protein: 25% Kcal/ Fat: 13%/ Carbohydrate: 62%) or HFD (Protein: 18% Kcal/ Fat: 45%/Carbohydrate: 36%) for 28 weeks to assess temporal changes in plasma sPRR and Ang II quantified by ELISA, and SBP measured by telemetry. Phenotype of T2D was established based on changes in body weight, glucose tolerance test, and plasma insulin and lipid levels. Vascular stiffness was measured in carotid arteries by pressure myography.

Results

By Week 16, a T2D phenotype was evident in HFD mice with greater exacerbation in males than in females. After Week 20, plasma sPRR started to increase in HFD male mice (4±3 vs. 3±1 ng/day; P<0.05) and remained elevated until Week 28 (5±3 vs. 3±.1 ng/day; P<0.05). No significant changes were observed in females. These changes paralleled increases in Ang II and SBP only in males [Ang II (HFD: 131±20 vs. NFD: 59±12 pg/day; P<0.05), SBP (HFD: 135 ±7 vs. NFD: 115± 2mmHg; P<0.001)] but not in females. Males on HFD also showed significant decreases in carotid compliance and distensibility. After Week 20, urinary angiotensinogen excretion (uAGT) started to increase only in HFD males compared to NFD; and by the end of the study, it was 4X higher, even in the absence of overt microalbuminuria.

Conclusion

In conclusion, in mice with HFD-induced T2D, plasma sPRR contributes to marked sex differences in systemic Ang II, SBP, and vascular stiffness. Concomitant uAGT differences support the concept of sexual dimorphism of intrarenal RAS activation. Plasma sPRR may reflect the status of systemic RAS and anticipate vascular complications during T2D.

Funding

  • NIDDK Support