CAPTOPRIL AND ANGIOTENSIN-II RECEPTOR ANTAGONIST THERAPY IN A PACING MODEL OF HEART-FAILURE

Twenty-four splenectomized dogs were subjected to rapid right ventricu lar pacing (RRVP) at 250 beats/min for five weeks. During the final th ree weeks, four groups of six dogs were untreated or treated with capt opril alone, with the angiotensin II type 1 (AT(1)) receptor antagonis t L158,809 alone or with the two drugs combined by constant intravenou s infusion. Hemodynamic studies were carried out during light anesthes ia at baseline, and after two and five weeks of pacing. Total vascular capacitance and stressed blood volume were calculated from the mean c irculatory filling pressure during transient circulatory arrest after acetylcholine administration at three different circulating volumes. C entral blood volume and cardiac output were measured by thermodilution . Severe heart failure was present in the untreated group after five w eeks of RRVP, characterized by low cardiac output and total vascular c apacitance, high right atrial and pulmonary capillary wedge and mean c irculatory filling pressure, plus increased stressed and central blood volumes. While L158,809 had no effect, captopril alone or combined wi th L158,809 ameliorated the reduction in total vascular capacitance, a nd reduced right atrial and mean circulatory pressure and stressed blo od volume. Combined therapy reduced pulmonary capillary wedge pressure . Thus, angiotensin-converting enzyme inhibition with captopril was ef fective in this model of chronic low output heart failure, whereas AT( 1) receptor antagonism was not.