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

• Published in: Diabetes & vascular disease research Vol. 12; no. 1; p. 33
• Main Authors: Kibel, Aleksandar, Novak, Sanja, Cosic, Anita, Mihaljevic, Zrinka, Falck, John R, Drenjancevic, Ines
• Format: Journal Article
• Language: English
• Published: England 01-01-2015
• Subjects: 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; Hyperbaric oxygen therapy; angiotensin-(1-7); angiotensin II; epoxyeicosatrienoic acids
• ISSN: 1752-8984
• DOI: 10.1177/1479164114553424

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.