title: Transient impairment of dynamic renal autoregulation in early diabetes mellitus in rats.
abstract: Renal autoregulation is impaired in early (1 wk) diabetes mellitus (DM) induced by streptozotocin, but effective in established DM (4 wk). Furthermore nitric oxide synthesis (NOS) inhibition with N(G)-nitro-L-arginine methyl ester (L-NAME) significantly improved autoregulation in early DM but not in established DM. We hypothesized that autoregulation is transiently impaired in early DM because of increased NO availability in the kidney. Because of the conflicting evidence available for a role of NO in DM, we tested the hypothesis that DM reduces autoregulation effectiveness by reducing the spatial similarity of autoregulation. Male Long-Evans rats were divided into control (CON) and diabetic (DM; streptozotocin) groups and followed for either 1 wk (CON1, n = 6; DM1, n = 5) or 4 wk (CON4, n = 7; DM4, n = 7). At the end of the experiment, dynamic autoregulation was assessed in isoflurane-anesthetized rats by whole kidney RBF during baseline, NOS1 inhibition, and nonselective NOS inhibition. Kidney surface perfusion, monitored with laser speckle contrast imaging, was used to assess spatial heterogeneity of autoregulation. Autoregulation was significantly impaired in DM1 rats and not impaired in DM4 rats. L-NAME caused strong renal vasoconstriction in all rats, but did not significantly affect autoregulation dynamics. Autoregulation was more spatially heterogeneous in DM1, but not DM4. Therefore, our results, which are consistent with transient impairment of autoregulation in DM, argue against the hypothesis that this impairment is NO-dependent, and suggest that spatial properties of autoregulation may also contribute to reduced autoregulatory effectiveness in DM1.
authors.affiliation: Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, British Columbia, Canada;
authors.forename: Nicholas
authors.initials: N
authors.lastname: Mitrou
authors.affiliation: Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, British Columbia, Canada;
authors.forename: Sidney
authors.initials: S
authors.lastname: Morrison
authors.affiliation: Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, British Columbia, Canada;
authors.forename: Paymon
authors.initials: P
authors.lastname: Mousavi
authors.affiliation: Division of Nephrology and Immunology, University of Alberta, Edmonton, Alberta, Canada; and Department of Physiology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Branko
authors.initials: B
authors.lastname: Braam
authors.affiliation: Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, British Columbia, Canada; wcupples@sfu.ca.
authors.forename: William A
authors.initials: WA
authors.lastname: Cupples
mesh_terms: D000818:Animals; D001786:Blood Glucose; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D015971:Gene Expression Regulation, Enzymologic; D006706:Homeostasis / Q000502:physiology*; D007668:Kidney / Q000502:physiology*; D008297:Male; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D013997:Time Factors
chemical_list: D001786:Blood Glucose; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat
keywords: diabetes mellitus; laser speckle contrast imaging; nitric oxide; renal blood flow; synchronization