Effects of bucindolol on neurohormonal activation in congestive heart failure.
To examine the effects of beta-adrenergic blockade on neurohormonal activation in patients with congestive heart failure, 15 men had assessments of hemodynamics and supine peripheral renin and norepinephrine levels before and after 3 months of oral therapy with bucindolol, a nonselective beta antagonist. At baseline, plasma renin activity did not correlate with any hemodynamic parameter. However, norepinephrine levels had a weak correlation with left ventricular end-diastolic pressure (r = 0.74, p less than 0.01), stroke volume index (r = 0.61, p less than 0.02) and pulmonary vascular resistance (r = 0.54, p less than 0.05). Plasma renin decreased with bucindolol therapy, from 11.6 +/- 13.4 to 4.3 +/- 4.1 ng/ml/hour (mean +/- standard deviation; p less than 0.05), whereas plasma norepinephrine was unchanged, from 403 +/- 231 to 408 +/- 217 pg/ml. A wide diversity of the norepinephrine response to bucindolol was observed with reduction of levels in some patients and elevation in others. Although plasma norepinephrine did not decrease, heart rate tended to decrease (from 82 +/- 20 vs 73 +/- 11 min-1, p = 0.059) with beta-adrenergic blockade, suggesting neurohormonal antagonism at the receptor level. No changes in I-123 metaiodobenzylguanidine uptake occurred after bucindolol therapy, suggesting unchanged adrenergic uptake of norepinephrine with beta-blocker therapy. Despite reductions in plasma renin activity and the presence of beta blockade, the response of renin or norepinephrine levels to long-term bucindolol therapy did not predict which patients had improved in hemodynamic status (chi-square = 0.37 for renin, 0.82 for norepinephrine).(ABSTRACT TRUNCATED AT 250 WORDS)
Eichhorn
E J
EJ
Cardiac Catheterization Laboratory, Dallas Veterans Administration Hospital, Texas 75216.
McGhie
A L
AL
Bedotto
J B
JB
Corbett
J R
JR
Malloy
C R
CR
Hatfield
B A
BA
Deitchman
D
D
Willard
J E
JE
Grayburn
P A
PA
D019797:3-Iodobenzylguanidine; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000328:Adult; D006321:Heart / Q000000981:diagnostic imaging; D006333:Heart Failure / Q000000981:diagnostic imaging / Q000188:drug therapy*; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007457:Iodine Radioisotopes; D007462:Iodobenzenes; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood*; D011412:Propanolamines / Q000627:therapeutic use*; D011877:Radionuclide Imaging; D012083:Renin / Q000097:blood*; D012084:Renin-Angiotensin System / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D007457:Iodine Radioisotopes; D007462:Iodobenzenes; D011412:Propanolamines; D019797:3-Iodobenzylguanidine; C024307:bucindolol; D012083:Renin; D009638:Norepinephrine