Abstract
PUA is associated with renin angiotensin aldosterone system (RAAS) activation, which promotes hypertension and kidney disease in T1D. Our aims were to examine (1) the effect of an ANG II infusion on PUA and (2) the association between PUA and systemic and renal hemodynamic responses to ANG II over a wide range of T1D duration. In this post hoc analysis, blood pressure, PUA, GFRinulin and ERPFPAH were measured during a euglycemic clamp before and after an ANG II infusion (1 ng·kg-1·min-1) in participants with T1D: 49 young (26.2±5.5 years) and 62 older (66.0±7.9 years) adults and healthy controls (HC): 27 young (25.1±4.6 years), and 72 older (64.6±8.0 years) adults. ANG II infusion caused a greater decline in GFRinulin in older vs. younger adults with T1D; there was no such difference between older vs. younger HC adults. ANG II decreased PUA more in HC than T1D in both age groups (p<0.0001, Figure 1). Decreases in PUA in response to ANG II infusion did not correlate with changes in renal or systemic hemodynamic parameters. Our findings suggest that ANG II infusion reduces PUA, potentially through direct effects on the ANG II type 1 receptor (AT1R). The presence of T1D attenuates PUA lowering effects irrespective of diabetes duration, suggesting an interaction between hyperglycemia, RAAS signaling pathways and PUA. Further studies are required to better understand the effects of AT1R receptor signaling on PUA concentrations. Disclosure Y. Lytvyn: None. J.A. Lovshin: Consultant; Self; Eli Lilly and Company, Intarcia Therapeutics, Inc., Prometic Life Sciences Inc. Other Relationship; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk Inc. P. Bjornstad: Advisory Panel; Self; Horizon, XORTX. Consultant; Self; Bayer US, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company. L. Lovblom: None. A. Katz: None. A. Lytvyn: None. G. Boulet: Other Relationship; Self; Medtronic. M.A. Farooqi: None. A. Weisman: None. H.A. Keenan: Employee; Self; Sanofi Genzyme. M.H. Brent: Advisory Panel; Self; AbbVie Inc., Bayer Canada, Novartis Canada. Research Support; Self; Bayer Canada, Novartis Canada, Roche Canada. N. Paul: Consultant; Self; Bayer AG. V. Bril: Advisory Panel; Self; Akcea Therapeutics, Alexion Pharmaceuticals, Inc., Alnylam, CSL Behring. Consultant; Self; Pfizer Inc. Research Support; Self; Baxter, Biogen, Grifols, UCB, Inc. A. Advani: Advisory Panel; Self; Abbott, Boehringer Ingelheim International GmbH, Dexcom, Inc., Novo Nordisk A/S. Research Support; Self; Boehringer Ingelheim International GmbH. B.A. Perkins: Advisory Panel; Self; Abbott, Boehringer Ingelheim International GmbH, Boehringer Ingelheim International GmbH, Insulet Corporation. Research Support; Self; Boehringer Ingelheim International GmbH. Other Relationship; Self; Abbott, Boehringer Ingelheim International GmbH, Lilly Diabetes, Medtronic, Novo Nordisk Inc., Sanofi. D. Cherney: Other Relationship; Self; AbbVie Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Mitsubishi Tanabe Pharma Corporation, Prometic Life Sciences Inc., Sanofi. Funding JDRF (17-2013-312)
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