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 m easured at 1, 3, 7, and 21 days after the operation. Both LV/BW ratio and v entricular AM levels showed a significant increase from 1 day after the ope ration in the AB rats versus the sham-operated rats. Both increased in a ti me-dependent manner. The ventricular AM levels correlated with the LV/BW ra tio (r=0.76, P<0.01). The AM mRNA levels were highly expressed at 1 day aft er 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 sh owed a peak at 1 day after the operation in both groups. Then, we treated A B rats with an angiotensin-converting enzyme inhibitor (quinapril) in 2 dos es (1 and 10 mg.kg(-1).d(-1)) for 21 days. The quinapril treatment attenuat ed similarly both the LV/BW ratio and the ventricular AM levels. We also as sessed the effects of AM and hydralazine administration for 7 days on the L V/BW ratio and hemodynamics of AB rats. Both AM and hydralazine administrat ion reduced the blood pressure by approximate to 10% compared with the nont reated 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 level s are elevated by chronic pressure overload in a time-dependent manner conc omitant with the extent of LVH and that AM may play a pathophysiological ro le in the development of LVH in chronic pressure overload.