Opiate receptor inhibition improves the blunted baroreflex function in conscious dogs with right-sided congestive heart failure.
The endogenous opiate system is activated in congestive heart failure. because endogenous opioids are known to depress the baroreflex function, we conducted studies to determine whether the increased endogenous opioids play a role in causing the reduced baroreflex function that occurs in heart failure. Right-sided congestive heart failure was produced in 16 dogs by tricuspid avulsion and progressive pulmonary artery constriction. Seven sham-operated dogs were included for comparison. Baroreflex function was measured in the conscious dogs after pretreatment with either normal saline or an opiate-receptor antagonist by bolus administration of phenylephrine. The slope of the regression line relating systolic blood pressure to cardiac cycle (R-R) interval was taken as an index of baroreflex sensitivity. Plasma beta-endorphin was elevated in the dogs with heart failure (15.3 +/- 2.5 pmol/l) compared with the sham-operated dogs (4.2 +/- 0.4 pmol/l, p less than 0.001). The dogs with heart failure also exhibited a reduced baroreflex sensitivity (3.84 +/- 0.19 msec/mm Hg) after saline pretreatment when compared with the sham-operated dogs (10.86 +/- 1.20 msec/mm Hg, p less than 0.001). Administration of naloxone hydrochloride increased the baroreflex sensitivity of dogs with heart failure to 5.16 +/- 0.26 msec/mm Hg (p less than 0.01) but produced no significant effects in sham-operated dogs (11.36 +/- 1.42 msec/mm Hg). To further study the site of action for the effect of naloxone, we measured baroreflex sensitivity in the dogs with heart failure after pretreatment with naloxonazine, a selective mu-receptor antagonist, with ICI 154,129, a selective delta-receptor antagonist, or with naloxone methobromide, a quaternary analogue of naloxone that does not penetrate the blood-brain barrier.(ABSTRACT TRUNCATED AT 250 WORDS)
Sakamoto
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Department of Medicine, University of Rochester Medical Center, New York 14642.
Liang
C S
CS
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003243:Consciousness; D004285:Dogs; D004562:Electrocardiography; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D006333:Heart Failure / Q000503:physiopathology*; D009270:Naloxone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D010111:Oxymorphone / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011311:Pressoreceptors / Q000503:physiopathology*; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology*; D012018:Reflex / Q000502:physiology*
D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D010656:Phenylephrine; D009270:Naloxone; D004743:Enkephalin, Leucine; C034643:naloxonazine; C036405:ICI 154129; D010111:Oxymorphone