ANGIOTENSIN-CONVERTING ENZYME-INHIBITION MODULATES ENDOGENOUS ENDOTHELIN IN CHRONIC CANINE THORACIC INFERIOR VENA-CAVAL CONSTRICTION

Endothelin (ET) is a potent vasoconstrictor peptide which is elevated in plasma in congestive heart failure. Recent studies suggest an impor tant role for angiotensin II (Air) in the activation of ET in cultured cardiomyocytes. Chronic thoracic inferior vena caval constriction (TI VCC) is a model of reduced cardiac output that mimics the neurohumoral activation observed in congestive heart failure. We hypothesized that activation of the renin-angiotensin system in TIVCC plays a role in t he activation of ET and that the elevation of endogenous ET contribute s to the systemic and renal vasoconstriction that characterizes this m odel of venous congestion. We studied conscious dogs after 7 d of TIVC C in the presence or absence of chronic angiotensin converting enzyme inhibition with enalapril. TIVCC resulted in marked activation of plas ma AII and ET in plasma, right atrium, lung, and renal medulla which w as further localized to cardiomyocytes, pulmonary, and renal epithelia l cells. Chronic angiotensin converting enzyme inhibition abolished th e increases in plasma AII, and ET during TIVCC. Acute endothelin A rec eptor blockade with FR-139317 resulted in significant decreases in mea n arterial pressure and systemic vascular resistance in TIVCC. We conc lude that activation of the renin-angiotensin system contributes to th e activation of circulating and local ET in TIVCC and that this activa tion plays an important role in the regulation of arterial pressure an d systemic vascular resistance in this model of congestive failure.