Endogenous prostaglandin E2 metabolite levels, renin-angiotensin system and catecholamines versus acute hemodynamic response to captopril in chronic congestive heart failure.

Hemodynamic and hormonal responses to captopril were measured in 10 patients with severe chronic heart failure poorly controlled by digitalis and diuretics. After administration of a 25-mg dose, stroke volume (SV) increased from 53 +/- 7 to 63 +/- 9 ml (p less than 0.05), while pulmonary wedge pressure (PWP) decreased from 20 +/- 2 to 14 +/- 2 mm Hg (p less than 0.01). The hemodynamic changes were associated with increases in plasma renin activity (PRA; p less than 0.05) and in plasma levels of a novel bicyclo-prostaglandin E2 metabolite (bicyclo-PGE-m; p less than 0.01), whereas norepinephrine (NE) showed a falling tendency. In general, basal hemodynamic and basal hormonal levels did not correlate. Captopril-induced changes in mean artery pressure (MAP) and mean pulmonary artery pressure (mPAP) were positively correlated to pre-captopril PRA (r = 0.74, p less than 0.01; r = 0.64, p less than 0.05) and to changes in PRA (r = 0.85, p less than 0.01; r = 0.80, p less than 0.01) with a similar trend for angiotensin II (AII); decreases of systemic vascular resistance were more pronounced in patients with higher control NE levels (r = 0.62, p less than 0.05), the reduction of NE levels being highest in patients with higher basal concentrations (p less than 0.001); the captopril-induced decreases of mPAP and PWP were inversely related to basal bicyclo-PGE-m levels (r = 0.60, p less than 0.05; r = 0.61, p less than 0.05), and changes in mPAP were closely related to basal ratios of AII/bicyclo-PGE-m (r = 0.67, p less than 0.01). Thus, captopril exerts its acute beneficial hemodynamic effect by inhibiting the generation of AII, associated with toning down of sympathetic stimulation and increased production of vasodilating prostaglandins, such as PGE2. The relation between AII and PGE2-counteracting substances-might determine the hemodynamic response to captopril in the patients.