Objective:In animal studies, naloxone, an opioid receptor antagonist, improves tolerance to hemorrhagic shock. The purpose of this study was to determine whether naloxone would augment tolerance to hypotensive hypovolemic stress (lower body negative pressure [LBNP]) in healthy human males.Design:This study was a repeated measures design.Setting:The experiments were conducted in a laboratory setting.Subjects:Eight healthy male subjects were tested. The subjects' ages were 30 ± 4.0 yrs, height = 177 ± 7.0 cm, and weight = 75.5 ± 3.5 kg (mean ± SEM).Interventions:Subjects underwent two LBNP exposures terminated by the onset of vasodepression. At each of the exposures, using a double-blind procedure, the subjects received an intravenous injection of either saline placebo or naloxone in a dosage totaling 0.4 mg/kg.Measurements:Tolerance to the hypovolemic stress, heart rate, blood pressures, forearm blood flow, forearm vascular resistance were measured.Main Results:Naloxone reduced the tolerance to LBNP by 17%. Heart rate and blood pressure responses immediately before vasodepression were also attenuated by naloxone as compared with placebo. Forearm blood flow and vascular resistance were not altered by naloxone.Conclusion:Our results indicate that unlike animal models of hemorrhagic shock, blocking the opioid receptors in males reduced tolerance to a hypotensive hypovolemic stress.