Crucial role of nitric oxide synthases system in endothelium-dependent hyperpolarization in mice
| Autor: | Toyotaka Yada, Hiroto Yamagishi, Keiko Morikawa, Nobuyuki Yanagihara, Aya Takaki, Junko Ohashi, Hiroaki Shimokawa, Masato Tsutsui, Yoshinori Murayama, Ender Tekes |
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| Rok vydání: | 2008 |
| Předmět: |
Male
medicine.medical_specialty Vascular smooth muscle Endothelium Immunology Biopterin Mice Transgenic Models Biological Article Nitric oxide Mice chemistry.chemical_compound Dihydrobiopterin Enos Internal medicine medicine Animals Protein Isoforms Immunology and Allergy Mesenteric arteries Neurons biology Articles Hydrogen Peroxide biology.organism_classification Acetylcholine Mesenteric Arteries Electrophysiology Nitric oxide synthase medicine.anatomical_structure Endocrinology chemistry cardiovascular system biology.protein Female Endothelium Vascular Nitric Oxide Synthase circulatory and respiratory physiology |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 1540-9538 0022-1007 |
| Popis: | The endothelium plays an important role in maintaining vascular homeostasis by synthesizing and releasing several relaxing factors, such as prostacyclin, nitric oxide (NO), and endothelium-derived hyperpolarizing factor (EDHF). We have previously demonstrated in animals and humans that endothelium-derived hydrogen peroxide (H(2)O(2)) is an EDHF that is produced in part by endothelial NO synthase (eNOS). In this study, we show that genetic disruption of all three NOS isoforms (neuronal [nNOS], inducible [iNOS], and endothelial [eNOS]) abolishes EDHF responses in mice. The contribution of the NOS system to EDHF-mediated responses was examined in eNOS(-/-), n/eNOS(-/-), and n/i/eNOS(-/-) mice. EDHF-mediated relaxation and hyperpolarization in response to acetylcholine of mesenteric arteries were progressively reduced as the number of disrupted NOS genes increased, whereas vascular smooth muscle function was preserved. Loss of eNOS expression alone was compensated for by other NOS genes, and endothelial cell production of H(2)O(2) and EDHF-mediated responses were completely absent in n/i/eNOS(-/-) mice, even after antihypertensive treatment with hydralazine. NOS uncoupling was not involved, as modulation of tetrahydrobiopterin (BH(4)) synthesis had no effect on EDHF-mediated relaxation, and the BH(4)/dihydrobiopterin (BH(2)) ratio was comparable in mesenteric arteries and the aorta. These results provide the first evidence that EDHF-mediated responses are dependent on the NOSs system in mouse mesenteric arteries. |
| Databáze: | OpenAIRE |
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