Important Role of Endothelial Caveolin-1 in the Protective Role of Endothelium-dependent Hyperpolarization Against Nitric Oxide–Mediated Nitrative Stress in Microcirculation in Mice
| Autor: | Shigemoto Fujii, Takaaki Akaike, Yosuke Ikumi, Hiroki Saito, Shuhei Tanaka, Akiyo Ito, Hiroaki Shimokawa, Tomoaki Ida, Saori Sato, Shigeo Godo |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Vasodilator Agents Caveolin 1 030204 cardiovascular system & hematology Biological Factors chemistry.chemical_compound 0302 clinical medicine Enos Phosphorylation Cyclic GMP Mesenteric arteries Mice Knockout Guanosine biology Hyperpolarization (biology) Nitro Compounds Coronary Vessels Mesenteric Arteries Nitric oxide synthase medicine.anatomical_structure Nitrosative Stress cardiovascular system Cardiology and Cardiovascular Medicine Signal Transduction medicine.medical_specialty Nitric Oxide Synthase Type III Cardiomegaly Nitric Oxide Nitric oxide Microcirculation Proto-Oncogene Proteins p21(ras) 03 medical and health sciences Internal medicine medicine Animals Nitric Oxide Donors Pharmacology Endothelial Cells Isolated Heart Preparation biology.organism_classification Mice Inbred C57BL 030104 developmental biology Endocrinology chemistry Microvessels biology.protein Protein Processing Post-Translational Homeostasis |
| Zdroj: | Journal of Cardiovascular Pharmacology. 71:113-126 |
| ISSN: | 0160-2446 |
| Popis: | Aims Nitric oxide (NO) and endothelium-dependent hyperpolarization (EDH) play important roles in maintaining cardiovascular homeostasis. We have previously demonstrated that endothelial NO synthase (eNOS) plays diverse roles depending on vessel size, as a NO generating system in conduit arteries and an EDH-mediated system in resistance arteries, for which caveolin-1 (Cav-1) is involved. However, the physiological role of endothelial Cav-1 in microvessels remains to be elucidated. Methods and results We newly generated endothelium-specific Cav-1-knockout (eCav-1-KO) mice. eCav-1-KO mice showed loss of endothelial Cav-1/eNOS complex and had cardiac hypertrophy despite normal blood pressure. In eCav-1-KO mice, as compared to wild-type controls, the extent of eNOS phosphorylation at inhibitory Thr495 was significantly reduced in mesenteric arteries and the heart. Isometric tension and Langendorff-perfused heart experiments showed that NO-mediated responses were enhanced, whereas EDH-mediated responses were reduced in coronary microcirculation in eCav-1-KO mice. Immunohistochemistry showed increased level of 8-nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP), a marker of nitrative stress, in the heart from eCav-1-KO mice. S-guanylation of cardiac H-Ras in eCav-1-KO mice was also significantly increased compared with wild-type controls. Conclusions These results suggest that eCav-1 is involved in the protective role of EDH against nitrative stress caused by excessive NO to maintain cardiac microvascular homeostasis. |
| Databáze: | OpenAIRE |
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