title: Dissociation of the prostaglandin and renin angiotensin systems during captopril therapy for chronic congestive heart failure secondary to coronary artery disease.
abstract: Neurohumoral systems are activated as compensatory mechanisms in congestive heart failure (CHF). A close correlation has been reported between the renin angiotensin and prostaglandin systems in CHF. Furthermore, serum sodium concentration provided an excellent index of hormonal status. In this study, these relations were examined after acute and chronic blockade of renin angiotensin system with captopril. Eight patients with advanced CHF (New York Heart Association III or IV) were studied. Before captopril treatment, all hormone levels were elevated. Mean plasma renin activity was 24 +/- 7 ng Al/ml/hour, angiotensin concentration was 221 +/- 11 pg/ml and aldosterone concentration was 82 +/- 17 pg/ml. Plasma PGE2 metabolite was 1,425 +/- 321 pg/ml. A close correlation was observed between plasma angiotensin II and PGE2 metabolite levels (r = 0.7); inverse correlations existed between serum sodium concentration and PGE2 metabolite levels (r = -0.9) and with plasma renin activity (r = -0.6). Captopril therapy reduced the plasma angiotensin II level to 38 +/- 6 pg/ml and aldosterone concentration to 15 +/- 3 pg/ml, but did not affect plasma renin activity (31 +/- 10 ng Al/ml/hour) when measured in 1 week. Paradoxically, PGE2-metabolite levels increased further (to 3,031 +/- 346 pg/ml) despite blockade of the renin angiotensin system. Serum sodium concentration no longer correlated with hormone levels. These effects were sustained at 2 months of follow-up. Thus, captopril caused a dissociation between the renin angiotensin system and prostaglandin. The activation of prostaglandin is probably due to captopril's effect on prostaglandin biosynthesis and may contribute to captopril's sustained efficacy in CHF.
authors.affiliation: Division of Vascular Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: V J
authors.initials: VJ
authors.lastname: Dzau
authors.forename: S L
authors.initials: SL
authors.lastname: Swartz
mesh_terms: D000328:Adult; D000368:Aged; D002216:Captopril / Q000627:therapeutic use*; D003327:Coronary Disease / Q000150:complications*; D015232:Dinoprostone; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011458:Prostaglandins E / Q000097:blood*; D012084:Renin-Angiotensin System / Q000187:drug effects*
chemical_list: D011458:Prostaglandins E; D002216:Captopril; D015232:Dinoprostone