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

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... 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 js-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/1, p<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<0.001). Administration of naloxone hydrochloride increased the baroreflex sensitivity of dogs with heart failure to 5.16+±0.26 msec/ mm Hg (p<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 ,-receptor antagonist, with ICI 154,129, a selective A-receptor antagonist, or with naloxone methobromide, a quaternary analogue of naloxone that does not penetrate the blood-brain barrier. Like naloxone hydrochloride, naloxonazine increased baroreflex sensitivity (5.31+0.44 msec/mm Hg, p<0.01) in heart failure. However, this effect was not produced by ICI 154,129 or naloxone methobromide. The results indicate that the activated endogenous opiate system in heart failure plays a role in modulating the baroreflex. Naloxone probably exerts its effects on improving baroreflex function via an action on central g-opiate receptors. (Circulation 1989;80:1010-1015 D iminished baroreceptor reflexes have been well described in cases of congestive heart failure.1-4 However, the mechanisms by which this baroreflex dysfunction occurs are not