Drug Discovery for Overcoming Chronic Kidney Disease (CKD) : The Endothelin ET_B Receptor / Nitric Oxide System Functions as a Protective Factor in CKD
スポンサーリンク
概要
- 論文の詳細を見る
Accelerated cardiovascular disease (CVD) is a frequent complication of renal disease. Chronic kidney disease (CKD) develops hypertension and dyslipidemia, which in turn can contribute to the progression of renal failure. There is general agreement that endothelin-1 (ET-1), which acts through the two subtypes of receptor ETA and ETB, plays important physiological roles in the regulation of normal cardiovascular function and that excessive ET-1 production is linked to CVD and CKD. Although selective ETA or nonselective ETA/ETB receptor antagonisms have been recognized as a potential strategy for treatment of several cardiovascular disease, it remains unclear which of the antagonisms is suitable for the individuals with CKD because upregulation of the nitric oxide (NO) system via ETB receptor is responsible for renal function such as natriuresis, diuresis, and glomerular hemodynamics. Our findings clearly indicate that the blockade of ET receptors, in particular ETA-receptor antagonism, not only produces a potential renoprotective effect in CKD but also reduces the risk of CVD. In contrast, pharmacological blockade or genetic deficiency of ETB receptor seems to aggravate CKD and CVD in several experimental models of rats. Moreover, preliminary evidence in patients with CKD also suggests that both selective ETA- and nonselective ETA/ETB-receptor blockade decreases blood pressure but that selective ETA blockade has additional desirable effects on renal hemodynamics. Thus, at least in CKD, these findings support the notion that ETB receptor–mediated actions produce a renoprotective effect and that nonselective ETA/ETB-receptors blockade seem to offer no advantage over selective ETA antagonism, and if anything may potentially reduce the benefits.
- 2009-01-20
著者
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OHKITA Mamoru
Laboratory of Pathological and Molecular Pharmacology, Osaka University of Pharmaceutical Sciences
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TAKAOKA Masanori
Laboratory of Pathological and Molecular Pharmacology, Osaka University of Pharmaceutical Sciences
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MATSUMURA Yasuo
Laboratory of Pathological and Molecular Pharmacology, Osaka University of Pharmaceutical Sciences
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Takaoka Masanori
Department Of Internal Medicine Iii Osaka Medical College
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Teragaki M
Department Of Internal Medicine And Cardiology Osaka City University Graduate School Of Medicine
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Ohkita Mamoru
Laboratory Of Pathological And Molecular Pharmacology Osaka University Of Pharmaceutical Sciences
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Muro Takashi
Department Of Internal Medicine And Cardiology Osaka City University Medical School
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Matsumura Yasuo
Laboratory Of Pathological And Molecular Pharmacology Osaka University Of Pharmaceutical Sciences
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Matsumura Yasuo
Department Of Pharmacology Osaka University Of Phiarmaceutical Sciences
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Matsumura Y
Asahi Glass Co. Ltd. Tokyo Jpn
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Okabe Makoto
Third Division Department Of Internal Medicine Osaka Medical College
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Mori Tatsuhiko
Third Department Of Medicine Osaka Medical College
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Takagi Masahiko
Department Of Internal Medicine And Cardiology Graduate School Of Medicine Osaka City University
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Takaoka M
Laboratory Of Pathological And Molecular Pharmacology Osaka University Of Pharmaceutical Sciences
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Okabe Makoto
The Third Division Internal Medicine Osaka College
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Murata Takashi
Center For Diabetes National Hospital Organization Kyoto Medical Center
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Takeuchi Masaaki
Second Department Of Internal Medicine University Of Occupational And Environmental Health School Of
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Mori Tatsuhiko
Department Of Gastroenterology And Neurology Faculty Of Medicine Kagawa University
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Takaoka Masanori
Laboratory of Cell Biology, Osaka University of Pharmaceutical Sciences, Japan
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