Acute hemodynamic and hormonal effects of central versus peripheral sympathetic inhibition in patients with congestive heart failure

Indoramin, an α₁ antagonist, and guanabenz, an α₂ agonist, were given to 10 patients with severe congestive heart failure to compare the hemodynamic and hormonal effects of a reduction in sympathetic tone obtained through inhibition of postsynaptic α₁ receptors versus the decrease in sympathetic activity achieved by stimulating central or presynaptic peripheral α₂ adrenoceptors. Both drugs produced similar reduction in systemic arterial pressure. However, only indoramin significantly decreased systemic and pulmonary vascular resistances from 1529 ± 526 to 1071 ± 356 and from 721 ± 422 to 412 ± 257 dynes ± 5 ± cm^-5, respectively, and increased stroke index from 26.6 ± 9.5 to 33.3 ± 9.5 ml/m² (all p < 0.01). Heart rate fell significantly only after guanabenz. Plasma norepinephrine, unchanged after indoramin, fell in each patient after guanabenz: The mean value decreased from 746 ± 332 to 461 ± 255 pg/ml (p < 0.01). Plasma renin activity increased only after indoramin. The data demonstrate: (a) a decrease in sympathetic activity due to blockade of α₁ adrenoreceptors produces marked peripheral and pulmonary vasodilation; (b) noradrenergic transmitter release in heart failure is regulated by α₂ receptors; (c) an α₂-mediated decrease in sympathetic activity and in plasma norepinephrine has a bradycardic effect but does not produce a vasodilator effect. Although the acute hemodynamic effects of indoramin were more prominent than those of guanabenz, the more favorable neurohumoral effects of guanabenz suggest the possibility of long-term benefit in the treatment of heart failure.