title: Nitric oxide-angiotensin II interactions and renal hemodynamic function in patients with uncomplicated type 1 diabetes.
abstract: The objective is to elucidate the effect of nitric oxide (NO)-renin-angiotensin system (RAS) interactions on renal hemodynamic function in uncomplicated, type 1 diabetes mellitus (DM). In 14 salt-replete, male healthy volunteers (C) and 9 male DM patients on euglycemia, glomerular filtration rate (GFR), renal blood flow (RBF), filtration fraction (FF), and sodium excretion (UNaV) were measured at baseline and during a 90-min infusion of 3.0 μg·kg⁻¹·min⁻¹ NG-nitro-L-arginine-methyl-ester (L-NAME) after 3 days of pretreatment with either placebo (PL) or 50 mg losartan (LOS). Baseline GFR, RBF, and FF were higher in DM (P < 0.005). In the C group, PL + L-NAME caused declines in GFR (101 ± 3 to 90 ± 3 ml·min⁻¹·1.73 m⁻²), RBF (931 ± 22 to 754 ± 31 ml·min⁻¹·1.73 m⁻²), and UNaV (158 ± 12 to 82 ± 18 μmol/min) and an increase in FF (0.19 ± 0.02 to 0.21 ± 02; P < 0.001), which were not influenced by LOS pretreatment (P > 0.05 for LOS + L-NAME-C vs. PL + l-NAME-C). In DM, PL + L-NAME resulted in exaggerated renal effects, with changes in GFR (128 ± 3 to 104 ± 3 ml·min⁻¹·1.73 m⁻²), RBF (1,019 ± 27 to 699 ± 34 ml·min⁻¹·1.73 m⁻²), UNaV (150 ± 13 to 39 ± 14 μmol/min), and FF (0.22 ± 0.03 to 0.26 ± 0.02) that were significantly greater vs. PL + L-NAME-C (P < 0.005). LOS pretreatment blunted GFR, RBF, FF, and UNaV responses to L-NAME in DM (P < 0.005 vs. PL + L-NAME-DM), resulting in a response profile that was similar to PL + L-NAME and LOS + L-NAME in C (P > 0.05). Renal responses to L-NAME in uncomplicated, type 1 DM are exaggerated vs. C, consistent with an upregulation of NO bioactivity. LOS, without effects in C, prevents the accentuated actions of L-NAME in DM, thus indicating an augmented role for NO-RAS interactions in renal hemodynamic function in DM.
authors: Department of Clinical and Experimental Medicine, University of Parma Medical School, Parma, Italy. alberto.montanari@unipr.it
authors: Alberto
authors: A
authors: Montanari
authors: Giovanna
authors: G
authors: Pelà
authors: Luisa
authors: L
authors: Musiari
authors: Antonio
authors: A
authors: Crocamo
authors: Luisella
authors: L
authors: Boeti
authors: Aderville
authors: A
authors: Cabassi
authors: Almerina
authors: A
authors: Biggi
authors: David Z
authors: DZ
authors: Cherney
mesh_terms: D000328:Adult; D000804:Angiotensin II / Q000378:metabolism*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism* / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D005919:Glomerular Filtration Rate; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007668:Kidney / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D019808:Losartan / Q000008:administration & dosage; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage; D009318:Natriuresis; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D012079:Renal Circulation; D012084:Renin-Angiotensin System / Q000187:drug effects; D015398:Signal Transduction; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D015415:Biomarkers; D004791:Enzyme Inhibitors; D000804:Angiotensin II; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019808:Losartan; D019331:NG-Nitroarginine Methyl Ester
keywords: l-NAME; losartan; nitric oxide; renal hemodynamic function; renin-angiotensin system; type 1 diabetes mellitus