Adrenomedullin, an endogenous peptide, counteracts cardiovascular damage
| Autor: | Kotaro Ishibashi, Katsuyuki Ando, Kenji Kangawa, Toshiro Fujita, Tatsuo Shimosawa, Kazuo Kitamura, Yugo Shibagaki, Shigeaki Kato |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Male
medicine.medical_specialty Intimal hyperplasia Time Factors Genotype Vasodilation Blood Pressure Peptide hormone Biology Adrenomedullin Mice Downregulation and upregulation Physiology (medical) Internal medicine Renin–angiotensin system Adrenal Glands medicine Animals NADH NADPH Oxidoreductases Lung Mice Knockout Membrane Glycoproteins Angiotensin II NADPH Oxidases Proteins Sodium Dietary medicine.disease Phosphoproteins Coronary Vessels Peptide Fragments Mice Inbred C57BL Endocrinology Cardiovascular Diseases Knockout mouse NADPH Oxidase 2 Tyrosine Female Cardiology and Cardiovascular Medicine Peptides Reactive Oxygen Species |
| Zdroj: | Circulation. 105(1) |
| ISSN: | 1524-4539 |
| Popis: | Background — Adrenomedullin (AM), a potent vasodilator peptide, is produced by posttranslational splicing of pro-adrenomedullin together with proadrenomedullin N-terminal 20 peptide (PAMP), another hypotensive peptide. Although both AM and PAMP have the potential not only to decrease blood pressure but also to protect organs from damage, there is no direct evidence for their individual physiological roles in vivo. Methods and Results — Using knockout mice with the disruption of AM peptide alone, we investigated the organ-protective effect of AM. Although the AM −/− mutation in mice was embryonic lethal without any apparent phenotypic changes, AM +/− mice were viable and fertile; plasma and organ AM concentrations were almost half of those in AM +/+ mice. With the administration of angiotensin II (Ang II) on a high-salt diet for 12 days, marked perivascular fibrosis and intimal hyperplasia were found in coronary arteries of Ang II/salt–treated AM +/− mice, without the AM upregulation that was observed in Ang II/salt–treated AM +/+ mice. In AM +/− mice, Ang II/salt loading increased both urinary excretion of 8-hydroxydeoxyguanosine and isoprostane, markers of oxidative stress. Consistently, immunostaining of both p67phox and gp91phox, subunits of NAD(P)H oxidase and 3-nitrotyrosine, the metabolites of reactive oxygen species (ROS), and the generation of ROS measured by electron spin resonance spectroscopy apparently increased in the Ang II/salt–treated heart. These data suggested that the overproduction of oxidative stress might be involved in the cardiovascular changes induced by Ang II/salt loading. Conclusions — The evidence presented supports the hypothesis that endogenous AM possesses a protective action against cardiovascular damage, possibly through the inhibition of oxidative stress production. |
| Databáze: | OpenAIRE |
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