Acute hemodynamic and hormonal effects of central versus peripheral sympathetic inhibition in patients with congestive heart failure.
Indoramin, an alpha 1 antagonist, and guanabenz, an alpha 2 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 alpha 1 receptors versus the decrease in sympathetic activity achieved by stimulating central or presynaptic peripheral alpha 2 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 X s X cm-5, respectively, and increased stroke index from 26.6 +/- 9.5 to 33.3 +/- 9.5 ml/m2 (all p less than 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 less than 0.01). Plasma renin activity increased only after indoramin. The data demonstrate: (a) a decrease in sympathetic activity due to blockade of alpha 1 adrenoreceptors produces marked peripheral and pulmonary vasodilation; (b) noradrenergic transmitter release in heart failure is regulated by alpha 2 receptors; (c) an alpha 2-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.
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D005260:Female; D006143:Guanabenz / Q000494:pharmacology*; D006146:Guanidines / Q000494:pharmacology*; D006333:Heart Failure / Q000097:blood / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D007217:Indoramin / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood*
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D006146:Guanidines; D007211:Indoles; D007217:Indoramin; D006143:Guanabenz; D009638:Norepinephrine