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 oxygen uptake (VO2), are mediated through prostaglandins. Angiotensin (AT1) receptor blockers apparently do not share potentiation of this biosystem. 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, all nonsmokers and not taking ACE, AT1 receptor, or cyclooxygenase inhibitors, were randomized to receive placebo, enalapril (10 mg 2 times daily), losartan (50 mg/day), each of these 2 drugs plus aspirin (325 mg/day), aspirin, or the same preparations in a reverse order, each for 3 weeks, with a 3-week washout period between treatments. Pulmonary function and VO2 were assessed at the end of each treatment. In CHF, losartan and enalapril caused a similar improvement of VO2 and exercise tolerance, which was absent in controls and was counteracted by aspirin (prostaglandin inhibition) when obtained with enalapril and not with losartan. While on enalapril, we also detected an increase in the diffusing lung capacity for carbon monoxide, which correlated with changes in VO2 and was antagonized by aspirin, suggesting the 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 tolerance, but the mechanism seems to be dissociated from a prostaglandin biosystem activation. Losartan may represent an advancement in CHF because its efficacy on VO2 is similar to that of enalapril, but is not antagonized by aspirin.
Guazzi
M
M
Istituto di Cardiologia dell'Università degli Studi, Centro di Studio per le Ricerche Cardiovascolari del Consiglio Nazionale delle Ricerche, Fondazione Monzino, I.R.C.C.S., Milano, Italy.
Melzi
G
G
Agostoni
P
P
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001241:Aspirin / Q000494:pharmacology; D002311:Cardiomyopathy, Dilated / Q000150:complications*; D018592:Cross-Over Studies; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004311:Double-Blind Method; D004656:Enalapril / Q000627:therapeutic use*; D005080:Exercise Test; D006333:Heart Failure / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000150:complications*; D010101:Oxygen Consumption / Q000187:drug effects*; D011653:Pulmonary Diffusing Capacity / Q000187:drug effects; D012123:Pulmonary Ventilation / Q000187:drug effects; D015656:Respiratory Mechanics / Q000187:drug effects*
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D016861:Cyclooxygenase Inhibitors; D004656:Enalapril; D019808:Losartan; D001241:Aspirin