Chronic Administration of Adrenomedullin Attenuates Transition From Left Ventricular Hypertrophy to Heart Failure in Rats

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Abstract
Acute administration of adrenomedullin (AM) exerts beneficial hemodynamic, renal, and neurohormonal effects in heart failure (HF). However, chronic effects of AM administration on HF remain unknown. This study sought to examine the effect of chronic infusion of AM on progression of HF in rat. Human recombinant AM was administered by osmotic minipump for 7 weeks in the HF model of Dahl salt-sensitive rats. The effect was compared with vehicle and diuretic treatment group. Chronic AM infusion significantly decreased left ventricular end-diastolic pressure, right ventricular systolic pressure, right atrial pressure, and left ventricular weight/body weight ( P P P P P P P <0.01) treatment groups. These results suggest that endogenous AM plays a compensatory role in HF and that chronic AM infusion attenuates progression of left ventricular dysfunction and improves survival, at least in part, through inhibition of circulating and myocardial neurohormonal activation.