Endogenous opioids and baroreflex control in humans.

Pc, Rubin; McLean, Kathleen; Reid, JL

doi:10.1161/01.hyp.5.4.535

Cited by 33 publications

(12 citation statements)

References 24 publications

(17 reference statements)

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“…Twenty-one subjects (19 men and two women aged 24+1 [mean±SEM] years) were studied in three treatment groups: 0.15 mg/kg naloxone (n=14, subjects 1-14), 0.075 mg/kg naloxone (n=13, subjects 9-21), and placebo (n=11, subjects [4][5][6][7][8][9][10][11][12][13][14]. Thus, six subjects (subjects 9-14) were studied with both doses of naloxone, and all but three subjects in the higher dose naloxone group were also studied after placebo.…”

Section: Subjects and Methods Subjectsmentioning

confidence: 99%

“…The hemodynamic and MSNA responses of subjects during application of incremental LBNP (0, -5, -10, and -15 mm Hg) before and after administration of 0.15 mg/kg naloxone (subjects [1][2][3][4][5][6][7][8][9][10][11][12][13][14] and 0.075 mg/kg naloxone (subjects 9-21) are summarized in Tables 1 and 2 and Figures 1 and 2.…”

Section: Effects Ofnaloxone On Responses To Cardiopulmonarymentioning

confidence: 99%

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Naloxone potentiates cardiopulmonary baroreflex sympathetic control in normal humans.

Schobel

Oren

Mark

et al. 1992

Circulation Research

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Naloxone, an opioid antagonist, augments baroreflex mechanisms in animals; this occurrence suggests that endogenous opioids blunt baroreflex responses. Limited human studies suggest an inhibitory action of endogenous opioids on baroreflex-mediated vagal responses during arterial baroreceptor deactivation. To evaluate the potential effect of endogenous opioids on cardiopulmonary baroreflex mechanisms in humans, we measured arterial and central venous pressures, heart rate, and efferent muscle sympathetic nerve activity (MSNA, by peroneal microneurography) during unloading of cardiopulmonary baroreceptors with incremental lower body negative pressure (LBNP, from 0 to -15 mm Hg) and during the cold pressor test in 21 normal subjects (aged 24±1 [mean±SEM] years). In 14 subjects, we performed LBNP before and after naloxone (0.15 mg/kg i.v.) and placebo (n = 11) on separate days. In six of these 14 subjects and an additional seven subjects (n=13), studies were also performed before and after administration of a lower dose of naloxone (0.075 mg/kg i.v.) on separate days. Neither dose of naloxone significantly altered control arterial or central venous pressures or heart rate. Control MSNA was reduced after the higher but not after the lower dose of naloxone. Comparable reductions in central venous pressure were produced by LBNP in all groups before and after naloxone or placebo, whereas LBNP did not alter arterial pressure. Cardiopulmonary baroreflex sympathetic sensitivity, which was derived as the slope of the linear regression relation between percent change in total MSNA (units) per absolute change in central venous pressure (mm Hg) during incremental LBNP, was significantly augmented after both the high dose (from 18.6±4.7%o/mm Hg to 39.3±8.1%o/mm Hg, p=0.001) and low dose of naloxone, whereas placebo had no effect. MSNA responses to the cold pressor test were not altered by (1987)(1988)(1989)(1990) where baroreceptor and chemoreceptor afferents terminate, there has been increasing interest in the possibility that endogenous opioids are involved in the physiological regulation of baroreflex mecha-

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Section: Subjects and Methods Subjectsmentioning

confidence: 99%

Section: Effects Ofnaloxone On Responses To Cardiopulmonarymentioning

confidence: 99%

Naloxone potentiates cardiopulmonary baroreflex sympathetic control in normal humans.

Schobel

Oren

Mark

et al. 1992

Circulation Research

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“…The plasma noradrenaline concentration measured at the time of the fall in blood pressure produced by captopril was not significantly different either from the concentrations measured before captopril was given or from the corresponding values on the placebo day (Table 5). There is now considerable evidence to suggest that endogenous opioids modulate blood pressure control at the level of the brain stem by reducing baroreflex sensitivity (Rubin et al, 1981(Rubin et al, , 1983Petty & Reid, 1982). The absence of compensatory tachycardia in response to a fall in blood pressure produced by captopril is consistent with decreased baroreflex activity.…”

Section: Introductionmentioning

confidence: 93%

“…Opioid receptor agonists have been shown to lower blood pressure without producing a compensatory tachycardia both in animals and man (Petty & Reid, 1982;Rubin et al, 1983). Captopril inhibits carboxypeptidase, one of the enzymes responsible for the inactivation of enkephalins in vitro (Arregiu et al, 1979) and, more specifically, has also been shown to reduce the metabolism and increase the analgesic potency of metenkephalin (Stine et al, 1979 (Rubin et al, 1981) and also significantly increases baroreflex sensitivity during sodium nitroprusside infusion at this same time (Rubin et al, 1983). Since captopril has its maximum effect on blood pressure 1.5 h following administration, we concentrated data collection immediately before and 1.5 h following administration of captopril or placebo.…”

Section: Introductionmentioning

confidence: 99%

The influence of naloxone on the circulatory effects of captopril.

Pc¹,

Millar²,

Sturani³

et al. 1984

Brit J Clinical Pharma

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The fall in blood pressure produced by captopril is not accompanied by a compensatory tachycardia. Angiotensin converting enzyme may participate in the metabolism of endogenous opioids and these substances can lower blood pressure without reflex tachycardia. It is therefore possible that the hypotensive effect of captopril involves an action on endogenous opioid metabolism. The influence of naloxone, an opiate receptor antagonist, on the cardiovascular effects of captopril has been studied in nine normal volunteers. Mean blood pressure following a 70 degrees head up tilt 1.5 h after captopril was significantly lower than following placebo, but the blood pressure following the combination of captopril and naloxone differed from neither the placebo nor the captopril values. Blood pressures (mm Hg) were: placebo 97.7 +/‐ 5.9; captopril 83.3 +/‐ 14.2; captopril + naloxone 89.6 +/‐ 11.8. Heart rate (beats/min) following a 70 degrees head up tilt at 1.5 h was the same on all three treatments: placebo 83.4 +/‐ 21.1; captopril 83.3 +/‐ 16.5; captopril + naloxone 83.6 +/‐ 11.8. Maximum systolic blood pressure achieved during isometric exercise following captopril + naloxone was intermediate between, and did not differ significantly from, pressures obtained on the other two treatment days. We conclude that co‐administration of naloxone may attenuate the effect of captopril on blood pressure and that endogenous opioids could be involved in the actions of this drug.

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“…However, other investigators have shown that naloxone hydrochloride reduces baroreflex sensitivity in pentobarbital-anesthetized normal dogs,20 whereas it increases baroreflex sensitivity in normal cats2' and humans. 22 The reasons for the discrepant results are not known but may be related, at least in part, to the use of anesthetics, differences in animal species, or relative basal levels of endogenous opioids among the studies.…”

Section: D'iscussionmentioning

confidence: 99%

Opiate receptor inhibition improves the blunted baroreflex function in conscious dogs with right-sided congestive heart failure.

Sakamoto

Liang

1989

Circulation

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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 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

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Endogenous opioids and baroreflex control in humans.

Cited by 33 publications

References 24 publications

Naloxone potentiates cardiopulmonary baroreflex sympathetic control in normal humans.

Naloxone potentiates cardiopulmonary baroreflex sympathetic control in normal humans.

The influence of naloxone on the circulatory effects of captopril.

Opiate receptor inhibition improves the blunted baroreflex function in conscious dogs with right-sided congestive heart failure.

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