Endogenous Prostaglandin E2 Metabolite Levels, Renin-Angiotensin System and Catecholamines versus Acute Hemodynamic Response to Captopril in Chronic Congestive Heart Failure

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Abstract
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 ± 9ml(p < 0.05), while pulmonary wedge pressure (PWP) decreased from 20 ± 2 to 14 ± 2 mm Hg (p < 0.01). The hemodynamic changes were associated with increases in plasma renin activity (PRA; p < 0.05) and in plasma levels of a novel bicyclo-prostaglandin E2 metabolite (bicycle-PGE-m; p < 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 < 0.01; r = 0.64, p < 0.05) and to changes in PRA (r = 0.85, p < 0.01;r = 0.80, p < 0.01) with a similar trend for angiotensin II (All); decreases of systemic vascular resistance were more pronounced in patients with higher control NE levels (r = 0.62, p < 0.05), the reduction of NE levels being highest in patients with higher basal concentrations (p < 0.001); the captopril-induced decreases of mPAP and PWP were inversely related to basal bicyclo-PGE-m levels (r = 0.60, p < 0.05; r = 0.61, p < 0.05), and changes in mPAP were closely related to basal ratios of All/bicyclo-PGE-m (r = 0.67, p < 0.01). Thus, captopril exerts its acute beneficial hemodynamic effect by inhibiting the generation of All, associated with toning down of sympathetic stimulation and increased production of vasodilating prostaglandins, such as PGE2The relation between All and PGE2 – counteracting substances – might determine the hemodynamic response to captopril in the patients.