Activation of cardiorenal and pulmonary tissue endothelin-1 in experimental heart failure

Endothelin-1 (ET-1) is a peptide that has been implicated in congestive hea rt failure (CHF). Although increased concentrations of circulating ET-1 hav e been repeatedly demonstrated, the activation of local ET-1 in target tiss ues of CHF remains poorly defined. Our objective was to characterize ET-1 t issue concentrations and gene expression of prepro ET-1 in myocardial, rena l, and pulmonary tissue in rapid ventricular pacing-induced canine CHF. Pro gressive rapid ventricular pacing (38 days) resulted in impaired cardiovasc ular hemodynamics, increased atrial and left ventricular mass, decreased re nal sodium excretion, and increased ET-1 plasma concentrations (all P < 0.0 5). Tissue analysis revealed significant increases in local ET-1 during CHF in left ventricular, renal, and pulmonary tissue, whereas a moderate incre ase in left atrial ET-1 did not reach statistical significance. In contrast , prepro-ET-1 gene expression was increased more than threefold in pulmonar y tissue and more than twofold in left atrial myocardium with no increase i n left ventricular or renal gene expression. The present studies demonstrat e a differential pattern of ET-1 activation in cardiorenal and pulmonary ti ssue with a strong accumulation of ET-1 in kidney and lung during CHF. Alth ough the observed increase in left ventricular and renal ET-1 in associatio n with unaltered gene expression is consistent with increased uptake, pulmo nary and atrial tissue may contribute to increased circulating and local ET -1 in CHF.