title: Glomerular mesangial cell altered contractility in high glucose is Ca2+ independent.
abstract: In diabetes, loss of renal arteriolar smooth-muscle cell contractility leads to intraglomerular hypertension. In glomeruli isolated from streptozotocin (STZ)-induced diabetic rats, the mesangial cells (smooth muscle-like) display loss of contractile responsiveness to angiotensin II. This study examines the mechanistic relationship between altered mesangial cell contractility and vasopressor hormone-stimulated Ca2+ signaling in high glucose. Glomeruli were isolated from normal or STZ-induced diabetic rats to observe ex vivo mesangial cell contractile function. Also, rat mesangial cells were cultured (10-20 passages) in normal (5.6 mmol/l) or high (10-25.6 mmol/l) glucose for 1-5 days. Reduction of glomerular volume and decreased planar surface area of cultured mesangial cells in response to vasoconstrictor stimulation over 60 min were measured by videomicroscopy and personal computer-based morphometry. Contraction of glomeruli isolated from STZ-administered rat in response to endothelin (ET)-1 (0.1 mumol/l) or the Ca2+ ionophore A23187 (5 mumol/l) was impaired significantly compared with that in normal glucose. In the presence of arginine vasopressin (AVP) (1.0 mumol/l) or ET-1 (0.1 mumol/l), mesangial cells demonstrated a dose-dependent loss of contractile response to increasing glucose concentrations (5.6-25.6 mmol/l) within 24 h of high-glucose exposure, which was sustained for 5 days. Mesangial cells in high glucose were consistently smaller in size compared with those in normal glucose. Mesangial cells were preloaded with myo-[2-3H]inositol and intracellular [3H] inositol phosphate release in response to AVP (1.0 mumol/l) was analyzed by Dowex chromatography. Comparing cells in normal (5.6 mmol/l) verus high (25.6 mmol/l) glucose, we observed no significant difference in stimulated inositol phosphate levels from 10 to 60 s.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Depatment of Medicine, University of Toronto, Canada.
authors.forename: R D
authors.initials: RD
authors.lastname: Hurst
authors.forename: Z S
authors.initials: ZS
authors.lastname: Stevanovic
authors.forename: S
authors.initials: S
authors.lastname: Munk
authors.forename: B
authors.initials: B
authors.lastname: Derylo
authors.forename: X
authors.initials: X
authors.lastname: Zhou
authors.forename: J
authors.initials: J
authors.lastname: Meer
authors.forename: M
authors.initials: M
authors.lastname: Silverberg
authors.forename: C I
authors.initials: CI
authors.lastname: Whiteside
mesh_terms: D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology*; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000494:pharmacology; D005920:Glomerular Mesangium / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D005947:Glucose / Q000494:pharmacology*; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism; D007700:Kinetics; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D013997:Time Factors; D014661:Vasoconstriction
chemical_list: D016232:Endothelins; D007295:Inositol Phosphates; D001127:Arginine Vasopressin; D000001:Calcimycin; D005947:Glucose; D002118:Calcium