NDLI: Regulation of renal 12(S)-hydroxyeicosatetraenoic acid in diabetes by angiotensin AT1 and AT2 receptors.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Abdel-Rahman, Emaad M. Abadir, Peter M. Siragy, Helmy M.
Description	Country affiliation: United States Author Affiliation: Abdel-Rahman EM ( Department of Medicine, University of Virginia School of Medicine, Charlottesville, Virginia 22908-1409, USA.)
Abstract	Diabetes is associated with increased production of 12(S)-hydroxyeicosatetraenoic acid [12(S)-HETE]. The mechanisms involved in this process remain unclear. We hypothesized that hyperglycemia and angiotensin II (ANG II) regulate renal 12(S)-HETE production via a balance between angiotensin AT(1) and AT(2) receptors activities. Using a microdialysis technique, renal interstitial fluid (RIF) levels of ANG II and 12(S)-HETE were monitored in normal control and streptozotocin-induced diabetic rats at baseline and then weekly thereafter for 12 wk. In a second group of normal and diabetic rats, 3 wk after development of diabetes, we monitored RIF 12(S)-HETE levels in response to acute AT(1) receptor blockade with valsartan or AT(2) receptor blockade with PD123319 individually or combined. Two weeks after induction of diabetes there was a 404% increase in ANG II (P < 0.05), a 149% increase in 12S-HETE (P < 0.05), and a 649% increase in urinary albumin excretion (P < 0.05). These levels remained elevated throughout the study. PD123319 given alone had no effect on 12(S)-HETE. Valsartan decreased 12(S)-HETE by 61.6% (P < 0.0001), a response that was abrogated when PD123319 was given with valsartan. These data demonstrate that hyperglycemia increases renal ANG II and 12(S)-HETE levels. The increase in 12(S)-HETE is mediated via AT(1) receptor. The attenuation of the effects of AT(1) receptor blockade by PD123319 suggests that AT(2) receptor contributes to the downregulation of renal 12(S)-HETE production.
File Format	HTM / HTML
ISSN	03636119
e-ISSN	15221490
DOI	10.1152/ajpregu.90699.2008
Journal	AJP: Regulatory, Integrative and Comparative Physiology
Issue Number	5
Volume Number	295
Language	English
Publisher	American Physiological Society
Publisher Date	2008-11-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Discipline Physiology 12-hydroxy-5,8,10,14-eicosatetraenoic Acid Metabolism Diabetes Mellitus, Experimental Diabetic Nephropathies Kidney Receptor, Angiotensin, Type 1 Receptor, Angiotensin, Type 2 Angiotensin Ii Angiotensin Ii Type 1 Receptor Blockers Pharmacology Angiotensin Ii Type 2 Receptor Blockers Animals Blood Glucose Blood Pressure Drug Effects Body Weight Hypoglycemic Agents Imidazoles In Vitro Techniques Insulin Microdialysis Pyridines Rats, Sprague-dawley Tetrazoles Valine Analogs & Derivatives Valsartan Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Physiology Physiology (medical)

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