Interaction Between P450 Eicosanoids and Nitric Oxide in the Control of Arterial Tone in Mice
| Autor: | Andrey Ch. da Costa Goncalves, Maik Gollasch, Fung Ping Leung, Friedrich C. Luft, Hantz C. Hercule, Steven M. Weldon, Jasmin Seringer, Volkmar Gross, Yu Huang, Wolf-Hagen Schunck |
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| Rok vydání: | 2009 |
| Předmět: |
Male
Epoxide hydrolase 2 medicine.medical_specialty Charybdotoxin Endothelium Blood Pressure Mice Inbred Strains Vasodilation Kidney Nitric Oxide Apamin Muscle Smooth Vascular Nitric oxide Biological Factors Mice chemistry.chemical_compound Cytochrome P-450 Enzyme System Heart Rate Internal medicine Renin–angiotensin system medicine Animals Cytochrome P-450 Enzyme Inhibitors Mesenteric arteries Epoxide Hydrolases Mice Knockout Chemistry Arteries Hydrogen Peroxide Iberiotoxin Catalase Mesenteric Arteries NG-Nitroarginine Methyl Ester medicine.anatomical_structure Endocrinology Muscle Tonus cardiovascular system Eicosanoids lipids (amino acids peptides and proteins) Endothelium Vascular Peptides Cardiology and Cardiovascular Medicine |
| Zdroj: | Arteriosclerosis, Thrombosis, and Vascular Biology. 29:54-60 |
| ISSN: | 1524-4636 1079-5642 |
| DOI: | 10.1161/atvbaha.108.171298 |
| Popis: | Objective— Epoxyeicosatrienoic acids (EETs) serve as endothelial-derived hyperpolarizing factors (EDHF), but may also affect vascular function by other mechanisms. We identified a novel interaction between EETs and endothelial NO release using soluble epoxide hydrolase (sEH) −/− and +/+ mice. Methods and Results— EDHF responses to acetylcholine in pressurized isolated mesenteric arteries were neither affected by the sEH inhibitor, N-adamantyl-N′-dodecylurea (ADU), nor by sEH gene deletion. However, the EDHF responses were abolished by catalase and by apamin/charybdotoxin (ChTx), but not by iberiotoxin, nor by the cytochrome P450 inhibitor PPOH. All four EETs (order of potency: 8,9-EET >14,15-EET≈5,6-EET >11,12-EET) and all 4 dihydroxy derivatives (14,15-DHET≈8,9-DHET≈11,12-DHET >5,6-DHET) produced dose-dependent vasodilation. Endothelial removal or L-NAME blocked 8,9-EET and 14,15-DHET-dependent dilations. The effects of apamin/ChTx were minimal. 8,9-EET and 14,15-DHET induced NO production in endothelial cells. ADU (100 μg/mL in drinking water) lowered blood pressure in angiotensin II–infused hypertension, but not in L-NAME–induced hypertension. Blood pressure and EDHF responses were similar in L-NAME–treated sEH +/+ and −/− mice. Conclusions— Our data indicate that the EDHF response in mice is caused by hydrogen peroxide, but not by P450 eicosanoids. Moreover, P450 eicosanoids are vasodilatory, largely through their ability to activate endothelial NO synthase (eNOS) and NO release. |
| Databáze: | OpenAIRE |
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