Attenuated natriuretic response to adrenomedullin in experimental heart failure

Background: The recently discovered vasodilating and positive inotropic pep tide, adrenomedullin (ADM), has strong natriuretic actions. ADM-induced nat riuresis is caused by an increase in glomerular filtration rate and a decre ase in distal tubular sodium reabsorption. Although ADM is activated in hum an and experimental heart failure, the role of ADM in the kidney in heart f ailure remains undefined. Methods and Results: The present study was performed to determine the renal hemodynamic and urinary excretory actions of exogenously administered ADM in a canine model of acute heart failure produced by rapid ventricular paci ng. Experimental acute heart failure was characterized by a decrease in car diac output and an increase in pulmonary capillary wedge pressure with an i ncrease in plasma ADM concentration. Intrarenal infusion of ADM (1 and 25 n g/kg/min) induced an increase in urinary sodium excretion in the normal con trol dogs (change in urinary sodium excretion [Delta UNaV], +94.5 mu Eq/min during 1 ng/kg/min ADM infusion and +128.1 mu Eq/min during 25 ng/kg/min A DM infusion). In the acute heart failure dogs, intrarenal ADM infusion resu lted in an attenuated increase in urinary sodium excretion (Delta UNaV, +44 .8 mu Eq/min during ng/kg/min ADM infusion and +51.8 mu Eq/min during 25 ng /kg/min ADM infusion). Both glomerular and tubular actions of ADM were atte nuated in the acute heart failure group compared with responses in the norm al control group. Conclusion: The present study shows that the renal natriuretic responses to ADM are markedly attenuated in experimental acute heart failure. This stud y provides insight into humoral mechanisms that may promote sodium retentio n in heart failure via a renal hyporesponsiveness to natriuretic actions of ADM.