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)