Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/9276
Title: Diabetes-induced vascular hypertrophy is accompanied by activation of Na(+)-H(+) exchange and prevented by Na(+)-H(+) exchange inhibition.
Authors: Jandeleit-Dahm, K;Hannan, K M;Farrelly, C A;Allen, Terri J;Rumble, J R;Gilbert, Richard E;Cooper, Mark E;Little, P J
Affiliation: Department of Medicine, University of Melbourne, Austin and Repatriation Medical Centre-Repatriation Campus, West Heidelberg, Australia.
Issue Date: 8-Dec-2000
Citation: Circulation Research; 87(12): 1133-40
Abstract: Vascular disease often involves vessel hypertrophy with underlying cellular hypertrophy or hyperplasia. Experimental diabetes stimulates hypertrophy of the rat mesenteric vasculature, and we investigated the hypothesis that this hypertrophy is associated with activation of Na(+)-H(+) exchange (NHE) activity. We measured the NHE activity in isolated, intact blood vessels from control and streptozotocin-induced diabetic adult rats using concurrent myography and fluorescence spectroscopy. The role of inhibiting NHE activity in preventing the development of the mesenteric hypertrophy in streptozotocin-diabetic rats was investigated by administration of cariporide (100 mg/kg body weight per day in 3 doses by gavage) after induction of diabetes and subsequently determining vessel weight and structure. The weight of the mesenteric vasculature was not increased 1 week after streptozotocin treatment but was significantly increased by an average of 56% at 3 weeks. NHE activity in mesenteric arteries showed an enhanced maximal velocity (V:(max)) in diabetic vessels at 1 and 3 weeks (0.246+/-0.006 and 0. 238+/-0.007 versus 0.198+/-0.007 pH U/min) with no change in the apparent K:(m). Moreover, NHE-1 mRNA in mesenteric arterioles at 3 weeks after streptozotocin treatment was increased by >60% (55.8+/-6. 4 versus 91.3+/-12.3 fg). Administration of cariporide significantly reduced mesenteric vascular weight, the wall/lumen ratio, and mesenteric extracellular matrix accumulation in the diabetic animals. Our study shows that diabetes in vivo correlates with elevated NHE activity and mRNA in the mesenteric vasculature and furthermore that inhibition of this system prevents the hypertrophic response. These data suggest that NHE may be a target for therapeutic modulation of vascular changes in diabetes.
Internal ID Number: 11110770
URI: http://ahro.austin.org.au/austinjspui/handle/1/9276
URL: http://www.ncbi.nlm.nih.gov/pubmed/11110770
Type: Journal Article
Subjects: Animals
Anti-Arrhythmia Agents.pharmacology
Blood Vessels
Diabetes Mellitus, Experimental.chemically induced.complications.metabolism
Disease Models, Animal
Guanidines.pharmacology
Hydrogen-Ion Concentration
Hypertrophy.etiology.metabolism
Male
Mesenteric Arteries.drug effects.metabolism
Muscle, Smooth, Vascular.metabolism
Rats
Rats, Sprague-Dawley
Sodium-Hydrogen Antiporter.metabolism
Streptozocin
Sulfones.pharmacology
Appears in Collections:Journal articles

Files in This Item:
There are no files associated with this item.


Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.