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

Emaad M. Abdel-Rahman, Peter Abadir, Helmy M. Siragy

Research output: Contribution to journalArticle

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 AT1 and AT2 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 AT1 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 AT1 receptor. The attenuation of the effects of AT1 receptor blockade by PD123319 suggests that AT2 receptor contributes to the downregulation of renal 12(S)-HETE production.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume295
Issue number5
DOIs
StatePublished - Nov 2008
Externally publishedYes

Fingerprint

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid
Angiotensin Type 2 Receptor
Angiotensin Type 1 Receptor
Valsartan
Kidney
Angiotensin II
Extracellular Fluid
Hyperglycemia
Hydroxyeicosatetraenoic Acids
Microdialysis
Streptozocin
Albumins
Down-Regulation

Keywords

  • Angiotensin II
  • Diabetes mellitus
  • Kidneys
  • Urinary albumin excretion

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

@article{b89a83bfbce0480e9c2c7869ee6d7067,
title = "Regulation of renal 12(S)-hydroxyeicosatetraenoic acid in diabetes by angiotensin AT1 and AT2 receptors",
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 AT1 and AT2 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 AT1 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 AT1 receptor. The attenuation of the effects of AT1 receptor blockade by PD123319 suggests that AT2 receptor contributes to the downregulation of renal 12(S)-HETE production.",
keywords = "Angiotensin II, Diabetes mellitus, Kidneys, Urinary albumin excretion",
author = "Abdel-Rahman, {Emaad M.} and Peter Abadir and Siragy, {Helmy M.}",
year = "2008",
month = "11",
doi = "10.1152/ajpregu.90699.2008",
language = "English (US)",
volume = "295",
journal = "American Journal of Physiology",
issn = "0363-6135",
publisher = "American Physiological Society",
number = "5",

}

TY - JOUR

T1 - Regulation of renal 12(S)-hydroxyeicosatetraenoic acid in diabetes by angiotensin AT1 and AT2 receptors

AU - Abdel-Rahman, Emaad M.

AU - Abadir, Peter

AU - Siragy, Helmy M.

PY - 2008/11

Y1 - 2008/11

N2 - 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 AT1 and AT2 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 AT1 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 AT1 receptor. The attenuation of the effects of AT1 receptor blockade by PD123319 suggests that AT2 receptor contributes to the downregulation of renal 12(S)-HETE production.

AB - 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 AT1 and AT2 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 AT1 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 AT1 receptor. The attenuation of the effects of AT1 receptor blockade by PD123319 suggests that AT2 receptor contributes to the downregulation of renal 12(S)-HETE production.

KW - Angiotensin II

KW - Diabetes mellitus

KW - Kidneys

KW - Urinary albumin excretion

UR - http://www.scopus.com/inward/record.url?scp=57349165807&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=57349165807&partnerID=8YFLogxK

U2 - 10.1152/ajpregu.90699.2008

DO - 10.1152/ajpregu.90699.2008

M3 - Article

C2 - 18799632

AN - SCOPUS:57349165807

VL - 295

JO - American Journal of Physiology

JF - American Journal of Physiology

SN - 0363-6135

IS - 5

ER -