(Hypertension. 1999;33:1146-1152.)
© 1999 American Heart Association, Inc.
Scientific Contributions |
Ventricular Adrenomedullin Levels Correlate With the Extent of Cardiac Hypertrophy in Rats
From the Research Institute (A.M., T.N., F.Y., H.M., K.K.) and Department of Medicine (T.H., N.N.), National Cardiovascular Center, Suita, Osaka, and First Internal Medicine of Nara Medical School (A.M., K.D.), Nara, Japan.
Correspondence to Toshio Nishikimi, MD, Division of Hypertension, National Cardiovascular Center Research Institute, 5-7-1, Fujishirodai, Suita, Osaka 565-8565, Japan. E-mail nishikim{at}jsc.ri.ncvc.go.jp
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
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.
Key Words: adrenomedullin • gene expression • hypertrophy, left ventricular • pressure overload
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