Hyperbaric oxygenation modulates vascular reactivity to angiotensin-(1-7) in diabetic rats: potential role of epoxyeicosatrienoic acids

Aleksandar Kibel; Sanja Novak; Anita Cosic; Zrinka Mihaljevic; John R Falck; Ines Drenjancevic

doi:10.1177/1479164114553424

Hyperbaric oxygenation modulates vascular reactivity to angiotensin-(1-7) in diabetic rats: potential role of epoxyeicosatrienoic acids

Diab Vasc Dis Res. 2015 Jan;12(1):33-45. doi: 10.1177/1479164114553424. Epub 2014 Oct 17.

Authors

Aleksandar Kibel¹, Sanja Novak¹, Anita Cosic¹, Zrinka Mihaljevic¹, John R Falck², Ines Drenjancevic³

Affiliations

¹ Faculty of Medicine, University of Osijek, Osijek, Croatia.
² Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX, USA.
³ Faculty of Medicine, University of Osijek, Osijek, Croatia ines.drenjancevic@mefos.hr.

PMID: 25326234
DOI: 10.1177/1479164114553424

Abstract

Previously, a facilitating effect of hyperbaric oxygenation (HBO₂) on aortic ring responses to angiotensin-(1-7) in healthy rats was reported, with epoxyeicosatrienoic acids (EETs) possibly playing an important role. The aim of this study was to assess whether HBO₂ exerts similar effects in diabetic rats and to further explore the role of specific cytochrome P450 (CYP) enzymes in changes induced by HBO₂. Aortic relaxation to angiotensin-(1-7) was significantly higher in HBO₂ diabetic rats compared to control diabetic rats, while HBO₂ had no effect on angiotensin II contraction. N-methylsulphonyl-6-(2-propargyloxyphenyl/hexanamide inhibited the facilitation of angiotensin-(1-7) responses in HBO₂ rats, suggesting an important role of EETs in this modulation. mRNA expression of CYP2J3 and protein expression of CYP2C11 were significantly upregulated in HBO₂ diabetic rats, whereas CYP4A1, CYP4A2 and CYP4A3 mRNA and CYP2J3 protein expression was similar between groups. Mean arterial pressure, ferric reducing ability of plasma and Thiobarbituric Acid Reactive Substances levels and serum angiotensin-(1-7) concentrations were not significantly changed.

Keywords: Hyperbaric oxygen therapy; angiotensin II; angiotensin-(1-7); epoxyeicosatrienoic acids.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

8,11,14-Eicosatrienoic Acid / analogs & derivatives*
8,11,14-Eicosatrienoic Acid / metabolism
Amides / pharmacology
Angiotensin I / blood
Angiotensin I / pharmacology*
Angiotensin II / pharmacology
Animals
Aorta, Thoracic / drug effects
Aorta, Thoracic / metabolism
Aorta, Thoracic / physiopathology
Aryl Hydrocarbon Hydroxylases / antagonists & inhibitors
Aryl Hydrocarbon Hydroxylases / genetics
Aryl Hydrocarbon Hydroxylases / metabolism
Cytochrome P-450 Enzyme System / chemistry
Cytochrome P-450 Enzyme System / genetics
Cytochrome P-450 Enzyme System / metabolism
Cytochrome P450 Family 2
Diabetes Mellitus, Type 1 / complications
Diabetes Mellitus, Type 1 / metabolism
Diabetes Mellitus, Type 1 / physiopathology
Diabetes Mellitus, Type 1 / therapy*
Diabetic Angiopathies / prevention & control*
Enzyme Induction
Enzyme Inhibitors / pharmacology
Hyperbaric Oxygenation* / adverse effects
Male
Oxidative Stress
Peptide Fragments / blood
Peptide Fragments / pharmacology*
Rats, Sprague-Dawley
Steroid 16-alpha-Hydroxylase / antagonists & inhibitors
Steroid 16-alpha-Hydroxylase / genetics
Steroid 16-alpha-Hydroxylase / metabolism
Vascular Resistance / drug effects*
Vasoconstriction / drug effects
Vasodilation / drug effects
Vasodilator Agents / blood
Vasodilator Agents / pharmacology*

Substances

Amides
Enzyme Inhibitors
N-methylsulfonyl-6-(2-propargyloxyphenyl)hexanamide
Peptide Fragments
Vasodilator Agents
Angiotensin II
Cytochrome P-450 Enzyme System
Angiotensin I
Aryl Hydrocarbon Hydroxylases
CYP2C11 protein, rat
Cyp2j3 protein, rat
Cytochrome P450 Family 2
Steroid 16-alpha-Hydroxylase
8,11,14-Eicosatrienoic Acid
angiotensin I (1-7)