Pathophisiological study of new hypotensive peptide, adrenomedullin, using experimental medels
Grant-in-Aid for Scientific Research (C)
|Allocation Type||Single-year Grants|
Circulatory organs internal medicine
|Research Institution||Miyazaki Medical College|
SAKATA Junichiro Miyazaki Medical College, Research instructor, 医学部, 助手 (30253818)
|Project Period (FY)
1994 – 1996
Completed(Fiscal Year 1996)
|Budget Amount *help
¥2,100,000 (Direct Cost : ¥2,100,000)
Fiscal Year 1996 : ¥500,000 (Direct Cost : ¥500,000)
Fiscal Year 1995 : ¥800,000 (Direct Cost : ¥800,000)
Fiscal Year 1994 : ¥800,000 (Direct Cost : ¥800,000)
|Keywords||bioactive peptide / adrenomedullin / pathophysiology / ラジオイムノアッセイ / モノクロタリン / proadorenomedullin N-terminal 20 peptide / 高血圧自然発症ラット|
Adrenomedullin (AM) is a new bioactive peptide recently isolated from pheochromocytoma. Summary of research results are as following.
1) Using a sensitive radioimmunoassay system for rat AM,high concentrations of immunoreactive rat AM were detected in adrenal gland, lung and cardiac atrium. In lung and atrium, the immunoreactivity concentration in rat was about 6-10 times higher than that in human. Mean plasma concentration of immunoreactive rat AM was 3.60 <plus-minus> 0.34 fmol/ml (mean <plus-minus> SD). Analysis in adrenal gland, lung and atrium with reverse phase and gel filtration high performance liquid chromatography showed that most immunoreactive rat AM emerged as a single peak at a position exactly identical to that of authentic rat AM pept
2) In order to elucidate the role of AM in hypertension, concentrations of immunoreactive rat AM and AM messenger RNA levels in tissues of spontaneously hypertensive rats (SHR) were compared with those of age-matched Wistar Kyoto rats (WKY).
The AM immunoreactivity concentrations in adrenal gland and cardiac atrium were significantly higher in SHR than in WKY.The AM content of cardiac ventricle was also significantly higher in SHR than in WKY.The rat AM messenger RNA levels in adrenal gland and heart of SHR were also higher than those of WKY.
As for salt dependent hypertension, medel, Dahl salt-sensitive rats, the AM concentration in cardiac ventricle of the high-salt group was significantly higher than that of the low-salt group. The plasma AM concentration was also significantly higher in the high-salt group than in the low salt group. The plasma AM concentration correlated well with the weight of left ventricle. RNA blot analysis revealed that the AM mRNA level in cardiac ventricle of the high-salt group was higher than that of the low-salt group. These results suggest that AM participates in the mechanism to counteract the blood pressure elevation.
3) Proadrenomedullin N-terminal 20 peptide (PAMP) is a novel hypotensive peptide processed from an AM precursor. High concentrations of immunoreactive PAMP (ir-PAMP) were detected in rat cardiac atrium and adrenal gland by the radioimmunoassay (RIA) for rat PAMP.The mean plasma concentration of rat ir-PAMP was 3.8 <plus-minus> 0.3 fmol/ml. The ir-PAMP concentration in heart tissue of SHR was found to be increased compared with that of the control rat. The atrial concentration of ir-PAMP of SHR (5.66 <plus-minus> 0.78 fmol/mg) was significantly higher than that of the control (3.29 <plus-minus> 0.22 fmol/mg). Cardiac PAMP might have a role for the protection from systemic hyperte Less
Research Output (22results)