Naloxone potentiates cardiopulmonary baroreflex sympathetic control in normal humans.

Abstract

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-

Chronic μ-Opioid Receptor Stimulation in Humans Decreases Muscle Sympathetic Nerve Activity

“…In fact, even large doses of naloxone (10 mg IV) do not alter resting MSA, sympathetic baroreflex sensitivity, catecholamine plasma concentrations, arterial pressure, or heart rate. [12][13][14][15][16] In contrast, naloxone potentiates the increase in MSA during exercise and in response to lower-body negative pressure, indicating an inhibition of MSA by endogenous opioids during states of sympathetic activation. 15,17,18 In anesthetized animals, opioid agonists generally decrease sympathetic activity.…”

“…[12][13][14][15][16] In contrast, naloxone potentiates the increase in MSA during exercise and in response to lower-body negative pressure, indicating an inhibition of MSA by endogenous opioids during states of sympathetic activation. 15,17,18 In anesthetized animals, opioid agonists generally decrease sympathetic activity. In anesthetized dogs and cats, fentanyl (5 to 50 g/kg IV) decreases splanchnic nerve activity and catecholamine plasma concentrations 3,4,6,7,9 and inhibits baroreflex responses.…”

“…[3][4][5][6][7][8][9][10][11] Furthermore, under resting conditions, -opioid receptor blockade by naloxone, which attenuates the effects of endogenous opioids, does not change muscle sympathetic activity (MSA), arterial baroreflex gain, or catecholamine plasma concentrations in healthy volunteers. [12][13][14][15][16] Conversely, naloxone potentiates the increase in MSA during exercise and in response to lower-body negative pressure, indicating inhibition of MSA by endogenous opioids when the sympathetic nervous system is activated. 15,17,18 Moreover, during sympathetic activation in experimental congestive heart failure (CHF), -opioid receptor blockade attenuates both decreased adrenergic inotropic responsiveness and baroreflex sensitivity, whereas cardiac function is improved.…”

“…[12][13][14][15][16] Conversely, naloxone potentiates the increase in MSA during exercise and in response to lower-body negative pressure, indicating inhibition of MSA by endogenous opioids when the sympathetic nervous system is activated. 15,17,18 Moreover, during sympathetic activation in experimental congestive heart failure (CHF), -opioid receptor blockade attenuates both decreased adrenergic inotropic responsiveness and baroreflex sensitivity, whereas cardiac function is improved. 19 -21 Finally, in contrast to subjects with physiological endogenous opioid activity, naloxone administration in patients with CHF prevents an attenuated inotropic response to adrenergic stimulation.…”

Effect of erythropoietin on cardiovascular prognosis parameters in hemodialysis patients

“…The rate of sympathetic nerve discharge was expressed as the number of bursts per minute (burst frequency). SNA was also corrected for the heart rate and expressed as bursts per 100 heartbeats (burst incidence) [23]. All nerve recordings were analyzed by two independent investigators who were unaware of the study protocol.…”