naloxone and Hypovolemia

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.. This study was a repeated measures design.. The experiments were conducted in a laboratory setting.. 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).. 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.

Topics: Adult; Analysis of Variance; Blood Pressure; Double-Blind Method; Forearm; Hemodynamics; Humans; Hypovolemia; Lower Body Negative Pressure; Male; Naloxone; Narcotic Antagonists; Prospective Studies; Regional Blood Flow; Shock, Hemorrhagic

In the present study we investigated, the effect of third ventricle injections of IL-1beta on water intake, in rats, induced by three different physiological stimuli: dehydration induced by water deprivation, hypernatremia associated with hyperosmolarity induced by intragastric salt load, and hypovolemia produced by subcutaneous polytethyleneglycol administration. Central administration of IL-1beta at the doses of 4 and 8 ng reduced water intake in all three conditions studied. Third ventricle injections of IL-1beta (8 ng) were unable to diminish water intake in the groups of rats pretreated with central injections of the non-selective opioid antagonist naloxone (10 microg) in the three different conditions studied. Furthermore, the central administration of IL-1beta was neither able to modify the intake of a 0.1% saccharin solution when the animals were submitted to a "dessert test" nor to induce any significant locomotor deficit in the open-field test. These results suggest that the central activation of interleukin-1 receptors by IL-1beta is able to impair the thirst-inducing mechanisms triggered by the physiological stimuli represented by dehydration, hyperosmolarity and hypovolemia. These results lead us to conclude that the antidipsogenic effects observed following central administration of IL-1beta require the functional integrity of the brain opiatergic system.

Topics: Animals; Body Temperature; Dehydration; Dose-Response Relationship, Drug; Drinking; Humans; Hypernatremia; Hypovolemia; Injections, Intraventricular; Interleukin-1; Male; Motor Activity; Naloxone; Narcotic Antagonists; Rats; Rats, Wistar; Saccharin; Water Deprivation

After an initial compensatory phase, hemorrhage reduces blood pressure due to a widespread reduction of sympathetic nerve activity (decompensatory phase). Here, we investigate the influence of intracerebroventricular naloxone (opioid-receptor antagonist) and morphine (opioid-receptor agonist) on the two phases of hemorrhage, central and peripheral hemodynamics, and release of vasopressin and renin in chronically instrumented conscious sheep. Adult ewes were bled (0.7 ml x kg(-1) x min(-1)) from a jugular vein until mean arterial blood pressure (MAP) reached 50 mmHg. Starting 30 min before and continuing until 60 min after hemorrhage, either artificial cerebrospinal fluid (aCSF), naloxone, or morphine was infused intracerebroventricularly. Naloxone (200 microg/min but not 20 or 2.0 microg/min) significantly increased the hemorrhage volume compared with aCSF (19.5 +/- 3.2 vs. 13.9 +/- 1.1 ml/kg). Naloxone also increased heart rate and cardiac index. Morphine (2.0 microg/min) increased femoral blood flow and decreased hemorrhage volume needed to reduce MAP to 50 mmHg (8.9 +/- 1.5 vs. 13.9 +/- 1.1 ml/kg). The effects of morphine were abolished by naloxone at 20 microg/min. It is concluded that the commencement of the decompensatory phase of hemorrhage in conscious sheep involves endogenous activation of central opioid receptors. The effective dose of morphine most likely activated mu-opioid receptors, but they appear not to have been responsible for initiating decompensation as 1) naloxone only inhibited an endogenous mechanism at a dose much higher than the effective dose of morphine, and 2) the effects of morphine were blocked by a dose of naloxone, which, by itself, did not delay the decompensatory phase.

Topics: Acute Disease; Analgesics, Opioid; Animals; Arginine Vasopressin; Blood Pressure; Central Venous Pressure; Consciousness; Dose-Response Relationship, Drug; Female; Heart Rate; Hemorrhage; Hypotension; Hypovolemia; Injections, Intraventricular; Morphine; Naloxone; Narcotic Antagonists; Receptors, Opioid; Recovery of Function; Renin; Sheep; Species Specificity; Vascular Resistance

Tuberoinfundibular peptide of 39 residues (TIP39) is a recently discovered neuropeptide identified on the basis of its ability to activate the PTH2 receptor, and it is thought to be the brain PTH2 receptor's endogenous ligand. The PTH2 receptor is highly expressed in the hypothalamus, suggesting a role in the modulation of neuroendocrinological functions. PTHrP, which also belongs to the PTH-related peptides family, stimulates arginine vasopressin (AVP) release. In the present study, therefore, we investigated the effect of centrally administered TIP39 on AVP release in conscious rats. Intracerebroventricular administration of TIP39 (10-500 pmol/rat) significantly suppressed the plasma AVP concentration in dehydrated rats, and the maximum effect was obtained 5 min after administration (dehydration with 100 pmol/rat TIP39, 4.32 +/- 1.17 pg/ml; vs. control, 8.21 +/- 0.70 pg/ml). The plasma AVP increase in response to either hyperosmolality [ip injection of hypertonic saline (HS), 600 mosmol/kg] or hypovolemia [ip injection of polyethylene glycol (PEG)] was also significantly attenuated by an intracerebroventricular injection of TIP39 (HS with 100 pmol/rat TIP39, 2.65 +/- 0.52 pg/ml; vs. HS alone, 4.69 +/- 0.80 pg/ml; PEG with 100 pmol/rat TIP39, 4.10 +/- 0.79 pg/ml; vs. PEG alone, 6.19 +/- 0.34 pg/ml). Treatment with naloxone [1.5 mg/rat, sc injection], a nonselective opioid receptor antagonist, significantly reversed the inhibitory effects of TIP39 on AVP release. These results suggest that central TIP39 plays an inhibitory role in the osmoregulation and baroregulation of AVP release and that intrinsic opioid systems are involved in its mechanism.

Topics: Animals; Arginine Vasopressin; Blood Pressure; Consciousness; Dehydration; Dose-Response Relationship, Drug; Hypothalamo-Hypophyseal System; Hypovolemia; Injections, Intraventricular; Male; Naloxone; Narcotic Antagonists; Neuropeptides; Rats; Rats, Sprague-Dawley; Water-Electrolyte Balance

Hypovolemia has been shown to decrease the dose requirement for propofol. This increased effect has been explained partially by an increased end organ sensitivity to the anesthetic effect of propofol. We used the opioid blocking agent naloxone to test the hypothesis that endogenous opioids may be involved in this increased sensitivity.. Thirty-two chronically instrumented rats were assigned randomly to either the hypovolemia (n = 16) or the control (n = 16) group.. After pretreatment of each rat in the two groups with either intravenous saline (n = 8) or naloxone (3 mg/kg; n = 8), an intravenous infusion of propofol (150 mg x kg(-1) x hr(-1)) was given until 5 secs of electrical suppression of the electroencephalographic signal was observed. Return of righting reflex was used to assess depth of anesthesia, and the propofol blood concentration was determined simultaneously with high-performance liquid chromatography.. The mean propofol blood concentrations at the return of righting reflex were significantly lower in the hypovolemic animals compared with the controls within both naloxone-treated (2.1 +/- 0.2 microg/mL vs. 2.9 +/- 0.2 microg/mL; p < .01) and saline-treated (2.2 +/- 0.1 vs. 3.0 +/- 0.2 microg/mL; p < .01) rats. The mean concentrations were not different between the saline- and naloxone-treated rats either within the hypovolemic group or within the control group.. The results of our study indicate that it is unlikely that the increased end organ sensitivity to propofol during hypovolemia is mediated by endogenous opioids, because it was not reversed by naloxone.

Topics: Anesthetics, Intravenous; Animals; Dose-Response Relationship, Drug; Drug Interactions; Electroencephalography; Hemodynamics; Hypovolemia; Infusions, Intravenous; Male; Naloxone; Narcotic Antagonists; Propofol; Rats; Rats, Wistar; Reflex