Impaired NO-mediated vasodilation with increased superoxide but robust EDHF function in right ventricular arterial microvessels of pulmonary hypertensive rats
| Autor: | Kousuke Endo, Keiji Naruse, Tatsuo Iwasaki, Satoshi Mohri, Masanori Hirota, Toyotaka Yada, Juichiro Shimizu, Taro Morimoto, Yousuke Inai, Fumihiko Kajiya, Yasuo Ogasawara, Masahito Kajiya, Takahiko Kiyooka, Tohru Ohe |
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| Rok vydání: | 2007 |
| Předmět: |
Male
Nitroprusside medicine.medical_specialty Physiology Heart Ventricles Hypertension Pulmonary Vasodilator Agents Vasodilation Nitric Oxide Microcirculation Muscle hypertrophy Rats Sprague-Dawley Biological Factors Superoxides Coronary Circulation Physiology (medical) Internal medicine Potassium Channel Blockers medicine Animals Enzyme Inhibitors Pressure overload Microscopy Video Monocrotaline Lung Hypertrophy Right Ventricular Superoxide Dismutase business.industry Tetraethylammonium Catalase medicine.disease Coronary Vessels Pulmonary hypertension Acetylcholine Rats Disease Models Animal NG-Nitroarginine Methyl Ester Endocrinology medicine.anatomical_structure Heart failure Circulatory system Nitric Oxide Synthase Cardiology and Cardiovascular Medicine business |
| Zdroj: | American Journal of Physiology-Heart and Circulatory Physiology. 292:H2737-H2744 |
| ISSN: | 1522-1539 0363-6135 |
| Popis: | Pulmonary hypertension (PH) causes right ventricular (RV) hypertrophy and, according to the extent of pressure overload, eventual heart failure. We tested the hypothesis that the mechanical stress in PH-RV impairs the vasoreactivity of the RV coronary microvessels of different sizes with increased superoxide levels. Five-week-old male Sprague-Dawley rats were injected with monocrotaline ( n = 126) to induce PH or with saline as controls ( n = 114). After 3 wk, coronary arterioles (diameter = 30–100 μm) and small arteries (diameter = 100–200 μm) in the RV were visualized using intravital videomicroscopy. We evaluated ACh-induced vasodilation alone, in the presence of Nω-nitro-l-arginine methyl ester (l-NAME), in the presence of tetraethylammonium (TEA) or catalase with or without l-NAME, and in the presence of SOD. The degree of suppression in vasodilation by l-NAME and TEA was used as indexes of the contributions of endothelial nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF), respectively. In PH rats, ACh-induced vasodilation was significantly attenuated in both arterioles and small aretries, especially in arterioles. This decreased vasodilation was largely attributable to reduced NO-mediated vasoreactivity, whereas the EDHF-mediated vasodilation was relatively robust. The suppressive effect on arteriolar vasodilation by catalase was similar to TEA in both groups. Superoxide, as measured by lucigenin chemiluminescence, was significantly elevated in the RV tissues in PH. SOD significantly ameliorated the impairment of ACh-induced vasodilation in PH. Robust EDHF function will play a protective role in preserving coronary microvascular homeostasis in the event of NO dysfunction with increased superoxide levels. |
| Databáze: | OpenAIRE |
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