COMPARISON OF CHANGES IN RESPIRATORY-FUNCTION AND EXERCISE OXYGEN-UPTAKE WITH LOSARTAN VERSUS ENALAPRIL IN CONGESTIVE-HEART-FAILURE SECONDARY TO ISCHEMIC OR IDIOPATHIC DILATED CARDIOMYOPATHY

In congestive heart failure (CHF), some of the effects of angiotensin- converting enzyme (ACE) inhibitors, such as an increase in exercise ox ygen uptake (VO2), are mediated through prostaglandins. Angiotensin (A T(1)) receptor blockers apparently do not share potentiation of this b iosystem. We tested whether losartan improves exercise VO2 in CHF and if the effect is the same as for enalapril. Sixteen men with CHF and 8 volunteers, ail nonsmokers and not taking ACE, AT(1) receptor, or cyc looxygenase inhibitors, were randomized to receive placebo, enalapril (10 mg 2 times daily), losartan (50 mg/day), each of these 2 drugs plu s aspirin (325 mg/day), aspirin, or the same preparations in a reverse order, each for 3 weeks, with a 3-week washout period between treatme nts. Pulmonary function and VO2 were assessed at the end of each treat ment. In CHF, losartan and enalapril caused a similar improvement of V O2 and exercise tolerance, which was absent in controls and was counte racted by aspirin (prostaglandin inhibition) when obtained with enalap ril and not with losartan. While on enalapril, we also detected an inc rease in the diffusing lung capacity for carbon monoxide, which correl ated with changes in VO2 and was antagonized by aspirin, suggesting th e possibility that a prostaglandin-mediated functional improvement of the alveolar capillary membrane contributes to the rise in VO2. Thus, losartan is as effective as enalapril for exercise VO2 and exercise to lerance, but the mechanism seems to be dissociated from a prostaglandi n biosystem activation. Losartan may represent an advancement in CHF b ecause its efficacy on VO2 is similar to that of enalapril, but is not antagonized by aspirin. (C) 1997 by Excerpta Medica, Inc.