title: Ventricular adrenomedullin levels correlate with the extent of cardiac hypertrophy in rats.
abstract: 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.
authors.affiliation: Research Institute and Department of Medicine, National Cardiovascular Center, Suita, Osaka, Nara, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Morimoto
authors.forename: T
authors.initials: T
authors.lastname: Nishikimi
authors.forename: F
authors.initials: F
authors.lastname: Yoshihara
authors.forename: T
authors.initials: T
authors.lastname: Horio
authors.forename: N
authors.initials: N
authors.lastname: Nagaya
authors.forename: H
authors.initials: H
authors.lastname: Matsuo
authors.forename: K
authors.initials: K
authors.lastname: Dohi
authors.forename: K
authors.initials: K
authors.lastname: Kangawa
mesh_terms: 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
chemical_list: 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