title: Juxtamedullary microvascular dysfunction during the hyperfiltration stage of diabetes mellitus.
abstract: This study was designed to identify and localize defects in renal microvascular function during the hyperfiltration stage of diabetes mellitus. Male Sprague-Dawley rats were injected intravenously with 65 mg/kg streptozotocin (IDDM rats) or vehicle (sham rats). IDDM rats received insulin (3 U.kg-1.day-1) via an osmotic minipump; sham rats received diluent. During the ensuing 2-wk period, blood glucose levels averaged 89 +/- 2 mg/dl in 33 sham rats and 290 +/- 13 mg/dl in 37 IDDM rats. At the end of this period, inulin clearance was elevated in eight IDDM rats (1.43 +/- 0.17 ml.min-1.g kidney wt-1) compared with six sham rats (0.78 +/- 0.05 ml.min-1.g kidney wt-1). The remaining animals served as tissue donors for study of the renal microvasculature using the in vitro blood-perfused juxtamedullary nephron technique. Kidneys from sham and IDDM rats were perfused with homologous blood at a renal arterial pressure of 110 mmHg. Juxtamedullary single-nephron glomerular filtration rate was higher in IDDM rats (41.5 +/- 5.4 nl/min) than in sham rats (25.4 +/- 2.4 nl/min). Afferent arteriolar inside diameter was greater in IDDM rats (34 +/- 2 microns) than in sham rats (22 +/- 1 microns); however, efferent arteriolar diameter did not differ between groups. The afferent arteriolar vasoconstrictor response to norepinephrine (NE) was attenuated in IDDM rats, relative to sham rats, over a wide range of NE concentrations. In contrast, NE evoked similar degrees of efferent vasoconstriction in IDDM and sham rats.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Physiology, Tulane University School of Medicine, New Orleans, Louisiana 70112.
authors.forename: K
authors.initials: K
authors.lastname: Ohishi
authors.forename: M I
authors.initials: MI
authors.lastname: Okwueze
authors.forename: R C
authors.initials: RC
authors.lastname: Vari
authors.forename: P K
authors.initials: PK
authors.lastname: Carmines
mesh_terms: D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000503:physiopathology; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003922:Diabetes Mellitus, Type 1; D005919:Glomerular Filtration Rate; D066298:In Vitro Techniques; D007679:Kidney Medulla / Q000098:blood supply*; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D010477:Perfusion; D011677:Punctures; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction
chemical_list: D009599:Nitroprusside; D009638:Norepinephrine