Ventricular adrenomedullin levels correlate with the extent of cardiac hypertrophy in rats.
We investigated the pathophysiological significance of adrenomedullin (AM) in the development of left ventricular hypertrophy (LVH). LVH was produced by aortic banding (AB) in rats. The left ventricular weight/body weight (LV/BW) ratio, ventricular AM peptide and mRNA levels, and hemodynamics were measured at 1, 3, 7, and 21 days after the operation. Both LV/BW ratio and ventricular AM levels showed a significant increase from 1 day after the operation in the AB rats versus the sham-operated rats. Both increased in a time-dependent manner. The ventricular AM levels correlated with the LV/BW ratio (r=0.76, P<0.01). The AM mRNA levels were highly expressed at 1 day after the operation in the AB rats but showed no difference from 3 to 21 days after the operation between the AB and sham groups. The plasma AM levels showed a peak at 1 day after the operation in both groups. Then, we treated AB rats with an angiotensin-converting enzyme inhibitor (quinapril) in 2 doses (1 and 10 mg. kg-1. d-1) for 21 days. The quinapril treatment attenuated similarly both the LV/BW ratio and the ventricular AM levels. We also assessed the effects of AM and hydralazine administration for 7 days on the LV/BW ratio and hemodynamics of AB rats. Both AM and hydralazine administration reduced the blood pressure by approximately 10% compared with the nontreated AB rats, but a reduction of the LV/BW ratio was observed only in the AM-treated group (P<0.05). These results suggest that ventricular AM levels are elevated by chronic pressure overload in a time-dependent manner concomitant with the extent of LVH and that AM may play a pathophysiological role in the development of LVH in chronic pressure overload.
Morimoto
A
A
Research Institute and Department of Medicine, National Cardiovascular Center, Suita, Osaka, Nara, Japan.
Nishikimi
T
T
Yoshihara
F
F
Horio
T
T
Nagaya
N
N
Matsuo
H
H
Dohi
K
K
Kangawa
K
K
D053607:Adrenomedullin; D000450:Aldosterone / Q000097:blood; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology; D001835:Body Weight; D015740:Calcitonin Gene-Related Peptide / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D003627:Data Interpretation, Statistical; D015870:Gene Expression; D006352:Heart Ventricles / Q000737:chemistry; D006439:Hemodynamics; D006830:Hydralazine / Q000008:administration & dosage / Q000494:pharmacology; D017379:Hypertrophy, Left Ventricular / Q000503:physiopathology*; D007150:Immunohistochemistry; D007546:Isoquinolines / Q000008:administration & dosage / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects; D008297:Male; D009929:Organ Size; D010455:Peptides / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D011355:Prodrugs; D000077583:Quinapril; D012333:RNA, Messenger / Q000032:analysis; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D012083:Renin / Q000097:blood; D044005:Tetrahydroisoquinolines; D013997:Time Factors; D017725:Ventricular Pressure
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D007546:Isoquinolines; D010455:Peptides; D011355:Prodrugs; D012333:RNA, Messenger; D044005:Tetrahydroisoquinolines; D053607:Adrenomedullin; D006830:Hydralazine; D000450:Aldosterone; D012083:Renin; D015740:Calcitonin Gene-Related Peptide; D000077583:Quinapril