Journal
DIABETES CARE
Volume 33, Issue 2, Pages 361-365Publisher
AMER DIABETES ASSOC
DOI: 10.2337/dc09-1303
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Funding
- Canadian Diabetes Association
- Kidney Foundation of Canada Scholarship
- CIHR/AMGEN Canada Kidney Research Chair at the University Health Network, University of Toronto
- Physicians' Services Foundation, courtesy Of the physicians of Ontario
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OBJECTIVE - Blockade of the renin-angiotensin system (RAS) plays an important role in preventing end-organ injury associated With diabetes. The recent development of direct renin inhibitors (DRIs) provides a new approach to block the RAS, but the effects of DRIs on renal and systemic vascular function in uncomplicated type I diabetes have not been elucidated. RESEARCH DESIGN AND METHODS - Renal hemodynamic function (inulin and paraaminohippurate clearance), augmentation index and pulse wave velocity, endothelial dependent vasodilatation (flow-mediated dilation [FMD]), and endothelial independent vasodilatation (response to sublingual nitroglycerin) were evaluated before and after administration of aliskiren (300 mg daily for 30 days) in 1.0 adult subjects with uncomplicated type I diabetes during clamped euglycemia (4-6 mmol/l) and hyperglycemia (9-11 mmol/l). RESULTS - in response to the DRI, plasma renin activity decreased (from 0.40 to 0.13 ng . ml(-1) . h(-1), P < 0.05) and plasma renin increased (from 5.2 to 75.0 ng/l, P < 0.05). Peripheral and central blood pressures decreased, and effective renal plasma now and glomerular filtration rate increased during clamped euglycemia and hyperglycemia (P < 0.05). The carotid augmentation index during clamped euglycemia decreased (from 26 +/- 6 to 20 +/- 5%, P < 0.05) as did pulse wave velocity during clamped hyperglycemia (from 7.8 +/- 0.6 to 6.8 +/- 0.5 m/s, P < 0.05). In response to the DRI, FMD increased during both clamped euglycemia (from 1.92 +/- 1.13 to 5.55 +/- 0.81%) and hyperglycemia (from 1.86 +/- 0.98 to 5.63 +/- 0.62) as did the vasodilatory response to sublingual nitroglycerin. CONCLUSIONS - DRIs exert a renal vasodilatory effect and improve parameters of systemic vascular function, Suggesting that blockade Of the RAS with this new class of agents has important functional effects in subjects with uncomplicated type I diabetes.
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