Relationship between contents of adrenomedullin and distributions of neutral endopeptidase in blood and tissues of rats in septic shock.
Adrenomedullin (ADM), a multifunction peptide with important roles in regulating cardiovascular homeostasis, has the vasodilatory properties and is of particular interest in the pathophysiology of sepsis. ADM levels in plasma and tissues are regulated by the proteolysis of neutral endopeptidase (NEP), the major enzyme of ADM degradation. We observed the NEP activity in the plasma, the activity and distribution of NEP and its mRNA expression in the tissues of rats in septic shock to study the possible role of NEP in elevating tissue ADM concentration during sepsis. ADM level increases progressively during sepsis except in the jejunum. Rats in early phase of shock (ES) showed diverse changes in tissue NEP activity. Plasma NEP activity, tissue NEP activity and its protein and mRNA expression in the left ventricle, aorta, jejunum and lung in the late phase of shock (LS) rats were lower than those in ES and the control, but no statistical change of NEP activity in the kidney was observed. The level of ADM was inversely correlated with NEP activity in the plasma, ventricle and aorta and positively correlated with NEP activity in the jejunum. Thus, in sepsis, the local concentration and action of ADM in tissues may be differentially regulated by NEP.
Jiang
Wei
W
Department of Physiology, Peking University Health Science Center, Beijing 100083, PR China.
Jiang
Hong-Feng
HF
Cai
Da-Yong
DY
Pan
Chun-Shui
CS
Qi
Yong-Feng
YF
Pang
Yong-Zheng
YZ
Tang
Chao-Shu
CS
D053607:Adrenomedullin; D000818:Animals; D001011:Aorta / Q000737:chemistry / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D002429:Cecal Diseases / Q000378:metabolism / Q000503:physiopathology; D002432:Cecum / Q000601:surgery; D002851:Chromatography, High Pressure Liquid; D015870:Gene Expression; D006352:Heart Ventricles / Q000737:chemistry / Q000378:metabolism; D007150:Immunohistochemistry; D007583:Jejunum / Q000737:chemistry / Q000378:metabolism; D007668:Kidney / Q000737:chemistry / Q000378:metabolism; D019344:Lactic Acid / Q000097:blood / Q000378:metabolism; D008026:Ligation; D016014:Linear Models; D008168:Lung / Q000737:chemistry / Q000378:metabolism; D008297:Male; D015260:Neprilysin / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D010455:Peptides / Q000032:analysis / Q000097:blood / Q000378:metabolism*; D011677:Punctures; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012772:Shock, Septic / Q000378:metabolism* / Q000503:physiopathology
D001786:Blood Glucose; D010455:Peptides; D053607:Adrenomedullin; D019344:Lactic Acid; D015260:Neprilysin