Overexpression of proadrenomedullin N-terminal 20 peptide blunts blood pressure rise and attenuates myocardial hypertrophy and fibrosis in hypertensive rats.
We developed a transgenic (Tg) rat model that overexpresses human proadrenomedullin N-terminal 20 peptide (PAMP) only and then compared the effects of unilateral nephrectomy followed by a high salt diet for five weeks in Tg and wild-type rats. We found that systolic blood pressure was significantly lower in Tg UNX rats and cardiac hypertrophy and myocardial fibrosis was also attenuated in Tg rats. Evaluation of gene expression showed suppression of cardiac local renin-angiotensin system (RAS) in Tg rat. These results suggest that in addition to reducing blood pressure, PAMP suppresses cardiac hypertrophy through negative regulation of the local cardiac RAS.
Cao
Yuan-Ning
YN
First Department of Internal Medicine, Miyazaki Medical College, University of Miyazaki, Kiyotake, 5200 Kihara, Miyazaki 889-1692, Japan.
Kuwasako
Kenji
K
Kato
Johji
J
Nishihira
Kensaku
K
Asada
Yujiro
Y
Eto
Tanenao
T
Kitamura
Kazuo
K
D053607:Adrenomedullin; D000818:Animals; D030801:Animals, Genetically Modified; D001794:Blood Pressure / Q000502:physiology*; D006332:Cardiomegaly / Q000378:metabolism / Q000473:pathology*; D004032:Diet; D005355:Fibrosis / Q000473:pathology; D006801:Humans; D006973:Hypertension / Q000378:metabolism*; D007668:Kidney / Q000166:cytology / Q000473:pathology; D009206:Myocardium / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism*; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism*; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D012084:Renin-Angiotensin System / Q000502:physiology; D012492:Salts / Q000008:administration & dosage; D019076:Transgenes
D010446:Peptide Fragments; D011498:Protein Precursors; D011506:Proteins; D012492:Salts; C088633:proadrenomedullin; D053607:Adrenomedullin