naloxone and Hemorrhage

The pedunculopontine tegmental nucleus (PPT) is involved in cardiovascular regulation. The presence of mu (μ) opioid receptors in the PPT nucleus has been determined. In the present study, the role of this nucleus in normotensive conditions and then the role of these receptors on cardiovascular function in hypotension induced by hemorrhage (HEM) were investigated.. Animals were divided into the following groups: Group 1: control, Group 2: HEM, Group 3: morphine at dose 100 nmol (a general opioid receptor agonist), Group 4: naloxone at dose 100 nmol (a general opioid receptor antagonist), Group 5: morphine + HEM, and Group 6: naloxone + HEM. After anesthesia, two femoral arteries were cannulated to record the cardiovascular parameters and blood withdrawal. Two minutes after induction of HEM, drugs were injected into the nucleus, and cardiovascular parameters were measured. Changes (Δ) in cardiovascular responses due to drug injection and HEM were calculated and compared to control and HEM groups.. HEM significantly reduced changes in systolic and mean arterial pressures and increased heart rate changes compared to control. Morphine microinjection in normotensive and HEM rats significantly decreased systolic blood pressure, mean arterial pressure, and heart rate, and naloxone significantly increased all these parameters.. This study showed that the PPT nucleus plays a role in modulating the cardiovascular responses induced by HEM. The µ opioid receptor of the PPT nucleus in the normotensive and HEM rats have inhibitory effects on blood pressure and heart rate mainly, and these effects are eliminated by naloxone microinjection.

Topics: Animals; Blood Pressure; Femoral Artery; Hemorrhage; Hypotension; Morphine Derivatives; Naloxone; Pedunculopontine Tegmental Nucleus; Rats; Receptors, Opioid; Receptors, Opioid, mu

The presence of opioid receptors in the cuneiform nucleus (CnF), which is a mesencephalic area, and their involvement in the central cardiovascular responses have been shown. Therefore, this study is designed to examine the possible role of mu- (μ) and delta- (δ) opioid receptors in the CnF in the cardiovascular responses in normotensive and hemorrhagic hypotensive rats. Following anesthesia and the recording of the blood pressure, the agonist and antagonist of μ- (morphine and naloxone) and δ- (D-Pen 2, 5]-Enkephalin hydrate (DPDPE) and naltridole) receptors were microinjected into the CnF. In the hemorrhagic groups, the drugs were microinjected into the nucleus 2 min after withdrawing 15 % of the total blood volume (TBV). Time-course changes (Δ) in the mean arterial pressure (MAP), systolic blood pressure (SBP), and heart rate (HR) were obtained and compared with the control and hemorrhage groups. Microinjecting morphine in both normotensive and hemorrhagic rats significantly decreased ΔSBP, ΔMAP, and ΔHR; also, naloxone significantly increased all these parameters. The cardiovascular effects of DPDPE and naltridole were not significant in the normotensive rats; however, DPDPE attenuated only the tachycardia induced by the hypotensive hemorrhage. The findings of this study revealed that the opioid receptors in the CnF had an inhibitory effect on the cardiovascular parameters in both normotensive and hypotensive hemorrhagic conditions and these effects were mostly mediated by μ-opioid receptors.

Topics: Analgesics, Opioid; Animals; Blood Pressure; Heart Rate; Hemorrhage; Hypotension; Male; Microinjections; Midbrain Reticular Formation; Morphine; Naloxone; Narcotic Antagonists; Rats; Rats, Wistar; Receptors, Opioid

This manuscript describes an innovative approach to public health nursing education. Health care delivery is radically shifting to non-acute, community-based settings, warranting a new-thinking graduate who is comfortable responding to societal trends in health and wellness. Graduates must confidently work to address social determinants of health to improve health outcomes and advance health equity.. We propose a unique pedagogy designed to prepare baccalaureate nursing students to work effectively in the community setting by developing seminars that address pressing, relevant public health initiatives.. We describe our experience integrating community-based Naloxone, Stop the Bleed, and Mental Health First Aid training to the curriculum. We outline a session designed to inform future health care providers about provision of care to suspected victims of human trafficking.. As a novice program, we have not formally evaluated the described pedagogy for specific outcome measures.. We include guidance for implementing a similar program and plans for future evaluation of this unique public health nursing pedagogy.. We are confident that future iterations of this pedagogy will continue to foster robust public health nursing skills among BSN students.

Topics: Curriculum; Delivery of Health Care; Education, Nursing, Baccalaureate; Hemorrhage; Human Trafficking; Humans; Mental Health; Naloxone; Public Health; Public Health Nursing; Students, Nursing

Some of the benefits of exercise appear to be mediated through modulation of neuronal excitability in central autonomic control circuits. Previously, we identified that six weeks of voluntary wheel running had a protective effect during hemorrhage (HEM), limiting both the hypotensive phase of HEM and enhancing recovery. The present study was undertaken to evaluate the role of opioid release in the lateral parabrachial nucleus (LPBN) on the response to severe HEM in chronically exercised (EX, voluntary) versus sedentary (SED) controls. Male Sprague Dawley rats were allowed either free access to running wheels (EX) or normal cage conditions (SED). After 6 weeks of "training" animals were instrumented with a bilateral cannula directed toward the dorsolateral pons and arterial catheters. After a recovery period, animals underwent central microinjection of either vehicle (VEH; n=3/group) or the opioid receptor antagonist naloxone (NAL; n=6/group) followed by withdrawal of 30% of their total estimated blood volume. Following VEH injection, the drop in MAP during and following HEM was significantly attenuated in the EX vs SED animals. Alternatively, NAL microinjection in the dorsolateral pons (20 μM, 200-500 nl) reversed the beneficial effect of EX on the HEM response. NAL microinjection in SED rats did not significantly alter the response to HEM. These data suggest chronic voluntary EX has a beneficial effect on the autonomic response to severe HEM which is mediated, in part, via EX-induced plasticity of the opioid system within the dorsolateral pons.

Topics: Animals; Blood Pressure; Heart Rate; Hemorrhage; Hypotension; Male; Microinjections; Naloxone; Narcotic Antagonists; Physical Conditioning, Animal; Pons; Rats; Rats, Sprague-Dawley; Receptors, Opioid

Children and adolescents with pulmonary hemorrhage are infrequently encountered in the emergency department (ED). We describe a case of a 16 year-old boy who presented to a pediatric ED with pulmonary hemorrhage and respiratory distress. The patient's unusual initial presentation resulted in the consideration of a broad differential diagnosis for his symptoms, including traumatic, neurological, respiratory, and toxicological causes. After resuscitation in the ED, a prolonged admission, and extensive testing, no cause could be found other than severe opioid toxicity. This case illustrates a rare, life-threatening presentation of opiod toxicity in a healthy adolescent and underlines the potentially serious nature of such exposures.

Topics: Adolescent; Analgesics, Opioid; Bronchi; Bronchoscopy; C-Reactive Protein; Disease Progression; Drug Overdose; Emergency Service, Hospital; Hemorrhage; Humans; Lung Diseases; Male; Morphine; Naloxone; Narcotic Antagonists; Regional Blood Flow; Status Asthmaticus

Severe haemorrhage leads to a reflex bradycardia and hypotension. This is thought to be protective, but is attenuated by both concomitant musculoskeletal injury and exogenous morphine. The aim of this study was to determine whether the injury-induced attenuation of the response to severe haemorrhage could be blocked by naloxone. Male Wistar rats, terminally anaesthetized with alphadolone/alphaxalone (19-20 mg kg(-1) h(-1)I.V.), were randomly allocated to one of four groups. In groups I and IV, haemorrhage was simple [40% of estimated total blood volume (BV)], while in groups II and III it was initiated 10 min after the onset of bilateral hindlimb ischaemia (a model of musculoskeletal injury). Groups I and II received 20 microl of 0.9% saline intracerebroventricularly (I.C.V.) immediately before haemorrhage, while groups III and IV received 20 microg of naloxone I.C.V., in the same volume. In group I, the bradycardia reached its peak after the loss of 32.8 +/- 0.3% BV (mean +/- S.E.M.). Blood pressure did not fall significantly until the loss of 15.0 +/- 3.0% BV. The response in group IV was not significantly different from group I. By contrast, the bradycardia was absent after similar blood losses in groups II and III, while hypotension was attenuated. These results indicate that naloxone, at a dose known to be effective in blocking mu-opioid receptors and preventing other aspects of the response to injury, does not prevent the injury-induced attenuation of the response to severe haemorrhage. Thus the attenuation of the response to blood loss by injury is unlikely to be mediated via the mu-opioid receptors.

Topics: Animals; Blood Pressure; Blood Volume; Bradycardia; Heart Rate; Hemorrhage; Hindlimb; Hypotension; Ischemia; Male; Musculoskeletal System; Naloxone; Narcotic Antagonists; Rats; Rats, Wistar; Receptors, Opioid, mu

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

High CO(2)-sensitivity, one of the major characteristics of the cerebrovascular bed, has been shown to be influenced by a variety of factors. There are no reports, however, on the involvement of the endogenous opioid peptides in the modulation of the CO(2)-sensitivity of the cerebral and spinal cord vessels, either in normotensive or, in hypotensive conditions. The effect of general opiate receptor blockade (1.0mg/kg naloxone, i.v.) on regional cerebrovascular CO(2)-sensitivity was studied with radiolabeled microspheres in 10 distinct brain and spinal cord regions of the anesthetized cat. The CO(2)-induced flow changes were investigated in normotensive, in moderately hypotensive (MAP=80 mmHg) and in deep hypotensive cats (MAP=40 mmHg). The systemic arterial pressure was lowered by hemorrhage. In the normotensive cats, opiate receptor blockade caused no changes in the vascular CO(2)-sensitivity in the investigated cerebral and spinal cord regions. In moderate hypotension, cerebral and spinal CO(2)-sensitivity was significantly reduced by the hemorrhage itself, but remained unaffected by the naloxone administration. In deep hemorrhagic hypotension, however, general opiate receptor blockade resulted not only in a further reduction of the already impaired CO(2)-sensitivity, but even in a reversal of the effect of CO(2) from flow increase to flow decrease. These results indicate that endogenous opioid peptides, which do not seem to influence cerebrovascular reactions in steady-state, normotensive conditions, may contribute significantly to the maintenance of the normal vasodilatory response of the cerebral and spinal cord vessels to CO(2) during hemorrhage-induced deep arterial hypotension.

Topics: Animals; Blood Pressure; Brain; Carbon Dioxide; Cats; Cerebrovascular Circulation; Female; Hemorrhage; Hypotension; Male; Naloxone; Narcotic Antagonists; Opioid Peptides; Spinal Cord

1. Severe blood loss initially lowers arterial pressure through a central mechanism that is thought to involve opioid and cholinergic neurons. The present study tested the hypothesis that simultaneous administration of a cholinergic agonist and an opioid receptor antagonist would produce a synergistic effect in the treatment of haemorrhage. Specifically, we tested whether choline, a precursor of acetylcholine, potentiates the pressor effect of the beta-endorphin derived peptide glycyl-glutamine (Gly-Gln) or the opioid receptor antagonist naloxone following acute haemorrhage. 2. Conscious rats were treated intracerebroventricularly (i.c.v.) with choline chloride (180 nmol) alone or combined with Gly-Gln (10 nmol) or naloxone (10 nmol) 2 min after blood withdrawal (2.5 mL/100 g bodyweight over 20 min) was completed; mean arterial pressure and heart rate were monitored for 30 min. 3. Combined treatment with choline and Gly-Gln elevated mean arterial pressure but did not affect heart rate significantly. Choline and Gly-Gln had no effect on cardiovascular function when administered alone to haemorrhaged rats or when given together to normotensive animals. Choline also potentiated the pressor and tachycardic effect of naloxone in haemorrhaged rats. 4. These data show that choline potentiates the pressor effect of Gly-Gln and naloxone in haemorrhaged rats.

Topics: Animals; Blood Pressure; Choline; Dipeptides; Drug Synergism; Female; Heart Rate; Hemorrhage; Male; Naloxone; Pressoreceptors; Rats; Rats, Sprague-Dawley

Severe hemorrhage lowers arterial pressure by suppressing sympathetic activity. The central mechanism that initially triggers the fall in arterial pressure evoked by hemorrhage is not well understood, although opioid neurons are thought to play a role. This study tested the hypothesis that hemorrhagic hypotension is mediated by delta opioid receptors in the ventrolateral periaqueductal gray (vlPAG), a region importantly involved in opioid analgesia. Depressor sites were first identified by microinjecting DL-homocysteic acid (20 nmol/0.1 microl) or beta-endorphin (0.5 nmol/0.1 microl) into the vlPAG of halothane-anesthetized rats. Consistent with earlier reports, DL-homocysteic acid injection into the caudal vlPAG lowered arterial pressure and heart rate; beta-endorphin evoked a comparable depressor response, but did not affect heart rate. Naloxone or selective opioid receptor antagonists were subsequently injected into the vlPAG 5 min before hemorrhage (1.9 or 2.5 ml/100 g of body weight over 20 min) was initiated using the same stereotaxic coordinates. Naloxone injection into the caudal vlPAG completely prevented the fall in arterial pressure evoked by hemorrhage. The response was dose-dependent and evident with both fixed volume and fixed pressure hemorrhage. The delta opioid receptor antagonist naltrindole inhibited hemorrhagic hypotension significantly in both conscious and anesthetized rats but mu and kappa receptor antagonists were ineffective. beta-Endorphin(1--27), an endogenous opioid receptor antagonist, was also significantly inhibitory. Naltrindole was ineffective when injected into the dorsolateral periaqueductal gray and did not influence cardiovascular function in nonhemorrhaged animals. These data support the hypothesis that hemorrhagic hypotension is mediated by delta opioid receptors in the vlPAG.

Topics: Animals; beta-Endorphin; Blood Pressure; Hemorrhage; Homocysteine; Male; Microinjections; Naloxone; Naltrexone; Narcotic Antagonists; Periaqueductal Gray; Rats; Rats, Sprague-Dawley; Receptors, Opioid, delta

Opioid receptors are activated during severe hemorrhage, resulting in sympathoinhibition and a profound fall in blood pressure. This study examined the location and subtypes of opioid receptors that might contribute to hypotension after hemorrhage. Intrathecal naloxone methiodide (100 nmol) abolished the fall in blood pressure after hemorrhage (1.5% of body wt; mean arterial pressure 122 +/- 8 mmHg after naloxone methiodide vs. 46 +/- 5 mmHg in controls, P < 0. 001). Intracisternal naloxone methiodide was less effective than intrathecal naloxone methiodide, whereas intravenous naloxone methiodide, which does not cross the blood-brain barrier, did not alter the fall in blood pressure after hemorrhage. These results demonstrate that spinal opioid receptors contribute to hypotension after hemorrhage but do not exclude supraspinal effects. In separate experiments, the subtype-specific opioid antagonists ICI-174864 (delta-antagonist), norbinaltorphimine (nor-BNI; kappa-antagonist), and H-D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP; mu-antagonist) were each administered intrathecally to determine the minimum dose that would attenuate hypotension during severe hemorrhage. These antagonists were effective at similar doses (3 nmol for CTOP, 6 nmol for ICI-174864, and 10 nmol for nor-BNI), although the binding affinities of these three different agents for their target receptors varied >1600-fold. Comparisons of the minimum effective doses of these antagonists in relation to their binding affinities provides strong evidence for the participation of delta-receptors in mediating hypotension after hemorrhage. In contrast, the dose at which nor-BNI was effective suggests an effect at delta-receptors but not kappa-receptors. The efficacy of CTOP, albeit at a high dose, also suggests an effect at mu-receptors.

Topics: Animals; Blood Pressure; Consciousness; Dynorphins; Endorphins; Enkephalin, Leucine; Heart Rate; Hemorrhage; Hypotension; Male; Naloxone; Narcotic Antagonists; Neural Inhibition; Rats; Rats, Inbred WKY; Receptors, Opioid, kappa; Receptors, Opioid, mu; Somatostatin; Spinal Cord; Sympathetic Nervous System

The possible involvement of the L-arginine-nitric oxide pathway and endogenous opioid mechanisms in the hemorrhagic hypotension- (HH) induced changes of hepatic arterial blood flow and vascular resistance was studied in cats. During HH hepatic arterial blood flow was significantly higher both in L-arginine- and naloxone-treated animals than in controls. Furthermore, HH induced a significant increase of the hepatic vascular resistance in the control group, which was prevented by L-arginine or naloxone treatment. Because inhibition of the nitric oxide synthesis by N(G)-nitro-L-arginine in normotensive cats induced a similar increase of the hepatic vascular resistance to that observed during HH in the control group, our results indicate that impairment of the endothelial function may be responsible for the hemorrhage-induced L-arginine- and naloxone-reversible hepatic arterial vasoconstriction. This hypothesis is consistent with our previous observations demonstrating the development of endothelial dysfunction in the feline hepatic artery during HH.

Topics: Animals; Arginine; Cats; Drug Evaluation, Preclinical; Hemorrhage; Hypotension; Liver; Male; Naloxone; Nitroarginine; Regional Blood Flow; Vasoconstriction

The effect of centrally induced opiate receptor blockade on regional cerebral blood flow (rCBF) was studied in anesthetized, ventilated cats during the course of hemorrhagic shock. The blood flow of the medulla and the parietal cortex was measured with the H2-gas clearance technique. Hemorrhagic shock was produced by lowering the systemic mean arterial pressure to 60 mmHg for 120 min by blood withdrawal. Central opiate receptor blockade was induced by 10 micrograms/kg intracerebroventricularly (i.c.v.) injected naloxone at the 60th min of the bleeding period. Cortical blood flow showed no improvement after i.c.v. naloxone administration. Medullary blood flow, however, increased significantly and approached the pre-bleeding control flow values following central opiate receptor blockade. The results indicate involvement of endogenous opioid mechanisms in the regulation of rCBF during hemorrhage and may provide an explanation for the previously described beneficial effects of naloxone in hemorrhagic shock.

Topics: Animals; Blood Pressure; Carbon Dioxide; Cats; Cerebral Cortex; Cerebrovascular Circulation; Female; Hemorrhage; Male; Medulla Oblongata; Naloxone; Narcotic Antagonists; Parietal Lobe; Pulmonary Gas Exchange; Receptors, Opioid; Shock, Hemorrhagic; Solitary Nucleus

The profound hypotension caused by acute hemorrhage is thought to involve opioid peptide neurons. In this study, we tested whether glycyl-L-glutamine [Gly-Gln; beta-endorphin-(30-31)], a nonopioid peptide derived from beta-endorphin processing, prevents the cardiovascular depression induced by hemorrhage in conscious and anesthetized rats. Previously, we found that Gly-Gln inhibits the hypotension and respiratory depression produced by beta-endorphin and morphine but does not affect opioid antinociception. Hemorrhage (2.5 ml/100 g body wt over 20 min) lowered arterial pressure in conscious rats (from 120.1 +/- 2.9 to 56.2 +/- 4.7 mmHg) but did not change heart rate significantly. Intracerebroventricular Gly-Gln (3, 10, or 30 nmol) pretreatment inhibited the fall in arterial pressure and increased heart rate significantly. The response was dose related and was sustained during the 35-min posthemorrhage interval. Pentobarbital sodium anesthesia potentiated the hemodynamic response to hemorrhage and attenuated the effect of Gly-Gln. Gly-Gln (10 or 100 nmol icv) did not influence arterial pressure or heart rate in normotensive rats. These data indicate that Gly-Gln is an effective antagonist of hemorrhagic hypotension.

Topics: Animals; Blood Pressure; Cerebral Ventricles; Dipeptides; Heart Rate; Hemorrhage; Hypotension; Injections, Intraventricular; Male; Naloxone; Neural Inhibition; Pulse; Rats; Rats, Sprague-Dawley; Stereoisomerism

The influence of naloxone-induced general opiate receptor blockade on hypothalamic blood flow autoregulation was investigated in anaesthetized, artificially ventilated, temperature controlled cats. In order to study the changes of the hypothalamic blood flow (H2-gas clearance technique) at the lower limit of autoregulation systemic arterial pressure was reduced in a stepwise manner to 100, 80, 60 and 40 mmHg, by haemorrhage. Autoregulatory mechanisms of the hypothalamic vessels remained effective and hypothalamic blood flow showed no significant reduction until the arterial pressure was reduced to 60 mmHg in the vehicle-treated control cats. General opiate receptor blockade by 1 mg kg-1 mL-1 i.v. injected naloxone resulted in a significant reduction of the autoregulatory capacity of the hypothalamic vessels: the blood flow followed passively the arterial pressure fall already from 100 mmHg mean arterial pressure. The effect of opiate receptor blockade on the upper limit of the autoregulation was studied during acute arterial hypertension, induced by angiotensin-II infusion (25 micrograms 0.1 mL-1 min-1 i.v.). Hypothalamic blood flow remained remarkably steady following angiotensin-II infusion in the saline-treated control animals. Naloxone pretreatment (1 mg kg-1 mL-1 i.v.), however, induced a significant downward shift of the upper limit of the autoregulation, and hypothalamic blood flow started to increase in the 125-145 mmHg arterial pressure range. The narrowing of the autoregulatory range following general opiate receptor blockade suggests an important role of endogenous opioid peptides in hypothalamic blood flow autoregulatory mechanisms both in hypotensive and in hypertensive conditions.

Topics: Angiotensin II; Animals; Carbon Dioxide; Cats; Central Venous Pressure; Cerebrovascular Circulation; Female; Hemorrhage; Homeostasis; Hypertension; Hypotension; Hypothalamus; Male; Naloxone; Narcotic Antagonists; Receptors, Opioid

The response of renal sympathetic nerve activity (RNA) to hemorrhage was examined in chronically-instrumented conscious rabbits. Hemorrhage was induced at a rate of 5 ml/kg per min until the mean arterial pressure fell below 40 mmHg. The mean arterial pressure then remained at around 80 mmHg until 10 ml/kg of hemorrhage (normotensive hemorrhage) before falling to below the pre-hemorrhagic control level (hypotensive hemorrhage). The RNA response showed a biphasic pattern, i.e., it increased during normotensive hemorrhage, then fell below the control level during hypotensive hemorrhage. To examine the mechanism involved in this decrease in RNA, naloxone (7.5 mumol/kg), an opioidergic receptor antagonist, was intravenously injected 1 min after the end of hemorrhage. Intravenous injection of naloxone caused an increase in mean arterial pressure and RNA to the level seen during normotensive hemorrhage. These results indicate that the decrease in RNA induced by hypotensive hemorrhage is mediated by opioidergic receptors. To determine whether the effects of naloxone are mediated via central or peripheral opioidergic receptors, naloxone was replaced by an equimolar solution of methylnaloxone, a form unable to cross the blood-brain barrier. Neither the mean arterial pressure nor RNA was significantly altered by administration of methyl naloxone. These results suggest that the effects of naloxone on both the RNA and the mean arterial pressure are mediated via central opioidergic receptors, i.e., the sympathoinhibition induced by hypotensive hemorrhage is mediated via the stimulation of central opioidergic receptors.

Topics: Animals; Blood Pressure; Heart Rate; Hemorrhage; Injections, Intravenous; Kidney; Male; Naloxone; Rabbits; Sympathetic Nervous System; Time Factors

Graded caval occlusion in conscious rabbits caused a biphasic haemodynamic response. Phase I was characterized by a fall in systemic vascular conductance so that arterial pressure was maintained. When cardiac output had fallen to 65 +/- 2% of its baseline level, phase II supervened. During phase II, conductance rose abruptly and arterial pressure fell to a life-threatening level (< or = 40 mm Hg). Fourth ventricular administration of either N-nitro-L-arginine methyl ester or naloxone prevented the occurrence of phase II. Fourth ventricular administration of L-arginine had no effect on the response to graded caval occlusion but was able to reverse the phase II blocking action of N-nitro-L-arginine methyl ester and naloxone. It is concluded that central nitrergic and opioid mechanisms interact to cause the vasodilatation characteristic of the decompensatory phase II of the cardiovascular response to acute hypovolaemia.

Topics: Animals; Arginine; Enkephalin, D-Penicillamine (2,5)-; Enkephalins; Hemodynamics; Hemorrhage; Naloxone; Narcotic Antagonists; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Synthase; Rabbits; Shock, Hemorrhagic

To find out if the opioids that are liberated during bleeding influence the concentrations of glucagon, insulin, somatostatin, corticosterone and glucose in rats, and if naloxone has any regulatory effect.. Laboratory study.. University hospital.. 56 Male Wistar rats.. Removal of blood corresponding to 2% of body weight through a catheter in the internal jugular vein. Before bleeding (n = 8), and at 5, 15 and 30 minutes afterwards (n = 16 at each time point, half of which had received naloxone 0.04 mg/ml, 0.7 ml/hour, for 10 minutes before bleeding and up to 30 minutes afterwards) rats were killed and samples of heart blood taken.. Concentrations of glucose, glucagon, insulin, somatostatin, and corticosterone in heart blood.. In the control group (saline) concentrations of glucose, glucagon and insulin increased significantly after bleeding, and had returned to baseline concentration by 30 minutes. Naloxone blocked the increases in the treated group.. Endogenous opioids, possibly endorphin, may be important in the acute regulation of blood glucose, glucagon and insulin concentrations after haemorrhage.

Topics: Animals; Blood Glucose; Corticosterone; Glucagon; Hemorrhage; Insulin; Male; Naloxone; Rats; Rats, Wistar; Somatostatin

We tested the hypothesis that the pressor effect of naloxone during acute hemorrhagic hypotension is mediated in part at peripheral sites. Experiments were performed in conscious, chronically prepared rabbits. First, we compared the hemodynamic response to peripheral injections of naloxone and naloxone methobromide during acute hemorrhagic hypotension. Naloxone methobromide, which does not enter the central nervous system, produced a lesser pressor effect than naloxone. Second, we looked for peripheral effects of naloxone after close-arterial injection into the hindquarter vasculature. Unlike i.v. injections, close-arterial injection of naloxone did not produce any significant hemodynamic changes during hemorrhagic hypotension. Finally, we compared the capacities of naloxone and naloxone methobromide to block the peripherally mediated cardiovascular response to i.v. methionine-enkephalin in nonhemorrhaged animals. The potency of the two compounds, in terms of their blockade of this peripherally mediated response, was similar. The results of the present study do not support a predominant peripheral role for naloxone during acute hemorrhagic hypotension in conscious rabbits.

Topics: Animals; Blood Pressure; Endorphins; Enkephalin, Methionine; Heart Rate; Hemodynamics; Hemorrhage; Hypotension; Male; Naloxone; Oxymorphone; Rabbits; Vascular Resistance

The present study was undertaken to investigate the changes in renal sympathetic nerve activity (RSNA) and adrenal sympathetic nerve activity (AdSNA) due to acute hemorrhage in anesthetized rabbits. The animals were bled to a mean arterial pressure (MAP) of 5.3 kPa within 10 minutes from the femoral artery. Acute hemorrhage elicited a biphasic responses of RSNA with an initial excitation and a late inhibition during hemorrhage. But hemorrhage only induced a lasting excitation in AdSNA which could be abolished by sino-aortic denervation (SAD). Bilateral vagotomy either before or after hemorrhage could reverse the late inhibition in RSNA, but did not abolish the excitation in AdSNA. Intravenous injection of naloxone or microinjection of naloxone into rostral ventrolateral medulla (RVLM) could reverse the late inhibition in RSNA, but had no significant effect on the initial excitation in RSNA and AdSNA during hemorrhage. Hemorrhage-induced heart (HR) change was similar that in RSNA, but could not be reversed by naloxone. These results indicate that the late inhibition in RSNA is mediated by inputs from vagus nerves and opiate peptide, particularly that in RVLM, and the excitation in AdSNA during hemorrhage is related to arterial baroreceptor reflex.

Topics: Adrenal Glands; Animals; Female; Hemorrhage; Kidney; Male; Medulla Oblongata; Naloxone; Rabbits; Sympathetic Nervous System; Vagus Nerve

During hemorrhagic hypotension, vascular resistance, plasma norepinephrine, and sympathetic nerve activity decrease. Naloxone reverses these effects. We hypothesized that increased sympathetic nerve activity was specific to naloxone and not secondary to the pressor response. Conscious rabbits were hemorrhaged until mean arterial pressure (MAP) was less than 40 mmHg, given naloxone (3 mg/kg) or saline, and monitored for 5 min. In some animals, we attenuated naloxone's pressor response with alpha-adrenergic blockade or mimicked the pressor response by infusion of phenylephrine. During nonhypotensive hemorrhage, heart rate and renal sympathetic nerve activity (RSNA) increased significantly. During hypotensive hemorrhage, RSNA decreased to significantly less than prehemorrhage control values. After saline treatment, RSNA did not increase. Naloxone significantly increased MAP and RSNA. alpha-Blockade reduced the pressor response to naloxone but not the increase in RSNA. Phenylephrine increased MAP to a level similar to naloxone, but RSNA remained suppressed. Reinfusion of hemorrhaged blood reduced RSNA in all groups treated with naloxone. These data suggest that hypotensive hemorrhage is associated with sympathoinhibition that is not transient. In addition, the pressor response to naloxone is not required for its sympathoexcitatory effects.

Topics: Analysis of Variance; Animals; Blood Pressure; Heart Rate; Hemodynamics; Hemorrhage; Kidney; Male; Naloxone; Phentolamine; Phenylephrine; Prazosin; Rabbits; Sympathetic Nervous System; Time Factors

We investigated the influence of endogenous opioids in the caudal ventrolateral medulla (CVLM) on the expression of the baroreflex response induced by the electrical stimulation (50 Hz, 0.2 ms, 11 V, 10 s) of the aortic depressor nerve. We used microinjection of selective opioid antagonists into the functionally identified depressor area of the CVLM in chloralose-anesthetized rabbits. Injection of vehicles or the mu-antagonist beta-funaltrexamine (0.3 nmol) into the CVLM had no effects, while naloxone (20 nmol), ICI 174,864 (delta-antagonist, 0.3 nmol) or nor-binaltorphimine (kappa-antagonist, 1 nmol) abolished the depressor response, but themselves all elicited a tonic depressor effect as well. In contrast, intravenous naloxone (5 mg/kg) induced a small but significant increase in arterial pressure and did not alter the depressor response. Hypotensive hemorrhage induced a decrease in arterial pressure similar to that seen with local injection of naloxone into the CVLM, but did not change the reflex, suggesting that the reflex abolition was not due to the decrease in basal arterial pressure per se. CVLM injection of glutamate (10 nmol) or the GABA-antagonist bicuculline (0.1 nmol), non-opioid agents which activate CVLM and induce a tonic depressor effect, also abolished the depressor response suggesting that the reflex abolition was secondary to general activation or disinhibition of the CVLM. Thus, although the CVLM is tonically inhibited by endogenous opioid inputs acting via delta- and kappa-receptors, our data provide no evidence that opioid neurons which provide input to this region constitute a specific and integral component in mediating the aortic depressor response. However, the more general role that opioids play in tonically influencing the resting level of activity in the CVLM, is nevertheless very important in enabling the normal expression of this baroreflex.

Topics: Animals; Aorta; Bicuculline; Blood Pressure; Electric Stimulation; Endorphins; Glutamates; Glutamic Acid; Hemorrhage; Male; Medulla Oblongata; Microinjections; Naloxone; Nervous System; Nervous System Physiological Phenomena; Rabbits

In the present study, the role of the endogenous opioid peptide systems in the regulation of blood pressure during standardized, stepwise hemorrhagic hypotension was investigated in anesthetized rats. Central as well as peripheral administration of naloxone resulted in an increase in the bleeding volumes required to reduce blood pressure. Bleeding volumes also increased after the peripheral injection of naloxone methobromide, an analog of naloxone that does not readily cross the blood-brain barrier. Following central administration of antisera against beta- and alpha-endorphin and dynorphin A(1-13), the amount of blood that had to be withdrawn to induce hypotension was elevated. In rats treated with an antiserum against [Met5] enkephalin or gamma-endorphin, bleeding volumes did not differ from those of rats treated with control serum. These data indicate that activation of central and possibly also of peripheral opiate receptors plays a role in the control of blood pressure during blood loss. Dynorphin A(1-13), beta- and alpha-endorphin, or closely related peptides might be the endogenous ligands for the receptors that are blocked by naloxone.

Topics: alpha-Endorphin; Animals; beta-Endorphin; Blood Pressure; Dynorphins; Endorphins; Enkephalin, Methionine; gamma-Endorphin; Hemorrhage; Hypotension; Immunization, Passive; Male; Naloxone; Oxymorphone; Peptide Fragments; Rats; Rats, Inbred Strains

We investigated possible interactions between arginine vasopressin (AVP) and endogenous opioid peptides during rapid hypotensive hemorrhage and subsequent opioid receptor blockade in conscious rabbits. Plasma AVP concentration did not change after normotensive hemorrhage but increased after hypotensive hemorrhage. Blockade of V1-AVP receptors (AVPX) did not affect prehemorrhage arterial pressure, heart rate, or hindquarter blood flow and vascular resistance. AVPX did not alter the hemodynamic response to hemorrhage or the blood loss required to reduce mean arterial pressure to less than 40 mmHg. However, hindquarter blood flow was higher and mean arterial pressure and hindquarter resistance lower after hypotensive hemorrhage in AVPX-treated animals. These differences were maintained after naloxone or saline injection. Naloxone increased mean arterial pressure and hindquarter resistance and decreased heart rate with or without AVPX. At 2 min postinjection, plasma AVP values were greater after saline than after naloxone. When naloxone's pressor response was reduced by alpha-adrenergic blockade, plasma AVP values were higher after naloxone than after saline. Thus AVP was not vital to maintenance of blood pressure during rapid normotensive hemorrhage or to the abrupt decrease in arterial blood pressure and resistance after rapid hypotensive hemorrhage. AVP release was important to spontaneous recovery from acute hypotensive hemorrhage but only of minor importance to naloxone's pressor response. Finally, AVP release appeared to be inhibited by endogenous opioids during acute hemorrhagic hypotension.

Topics: Animals; Arginine Vasopressin; Drug Interactions; Endorphins; Hemodynamics; Hemorrhage; Hypotension; Naloxone; Narcotic Antagonists; Rabbits; Rest

The interaction between opioid and prostanoid mechanisms in the control of cerebral hemodynamics was investigated in the conscious hypotensive piglet. Radiomicrospheres were used to determine regional cerebral blood flow (rCBF) in piglets pretreated with the opioid receptor antagonist, naloxone, or its vehicle, saline, during normotension, hypotension, and after the administration of indomethacin, a cyclooxygenase inhibitor, during hypotension. Hemorrhage (30 ml/kg) decreased systemic arterial pressure from 68 +/- 12 to 40 +/- 10 mm Hg but did not decrease blood flow to any brain region. Indomethacin treatment (5 mg/kg) of hypotensive piglets decreased blood flow to all brain regions within 20 min; this decrease in CBF resulted from increases in cerebral vascular resistance of 65 and 281% at 20 and 40 min after treatment, respectively. In hypotensive piglets, cerebral oxygen consumption was reduced from 2.62 +/- 0.71 to 0.53 +/- 0.27 ml 100 g-1 min-1 and to 0.11 +/- 0.04 ml 100 g-1 min-1 at 20 and 40 min following indomethacin, respectively. Treatment with naloxone (1 mg/kg) had no effect on rCBF, calculated cerebral vascular resistance, or cerebral oxygen consumption of normotensive or hypotensive piglets. However, decreases in CBF and oxygen consumption and increases in cerebral vascular resistance upon treatment of hypotensive piglets with indomethacin were attenuated in animals pretreated with naloxone. These data indicate that the removal of prostanoid modulation of an opioid-mediated constrictor influence on the cerebral circulation is a potential mechanism for the increase in cerebral vascular resistance that follows indomethacin treatment of hypotensive piglets.

Topics: Animals; Arteries; Blood Flow Velocity; Blood Pressure; Carbon Dioxide; Cardiac Output; Cerebrovascular Circulation; Cyclooxygenase Inhibitors; Endorphins; Hemorrhage; Hydrogen-Ion Concentration; Hypotension; Indomethacin; Microspheres; Naloxone; Oxygen; Prostaglandins; Swine; Vascular Resistance; Vasoconstriction

We have examined the influence of endogenous opioids on the basal and reflex control of arterial blood pressure in the pressor region of the rostral ventrolateral medulla (RVLM) of chloralose-anesthetized rabbits. We tested basal effects both in intact animals and after hypotensive hemorrhage. Bilateral administration of the opiod antagonist naloxone (20 nmol, 100 nl) directly into the RVLM induced a gradual and prolonged increase in mean arterial pressure (MAP) (+17 +/- 2 mmHg). This was preceded by a brief and mild depressor effect (-9 +/- 3 mmHg), which was attributable to a transient reduction in excitability immediately after naloxone injection. When naloxone was administered into the RVLM after hemorrhage (20 ml/kg), it improved recovery of MAP relative to saline controls, again producing a gradual, prolonged pressor response (+29 +/- 5 mmHg). The effect of naloxone on a baroreflex in intact animals was only transient, with a brief, nonsignificant attenuation of the reflex depressor response to aortic nerve stimulation. We conclude that endogenous opioids exert a tonic inhibitory influence on RVLM pressor neurons and that this input remains active after hemorrhage. The RVLM may thus be one site for the beneficial effects of naloxone in preventing circulatory decompensation after hemorrhage. In contrast, opioid neurons are not an essential component of baroreflex-mediated sympathoinhibition in the RVLM.

Topics: Animals; Aorta; Blood Pressure; Cardiovascular System; Endorphins; Glutamates; Glutamic Acid; Heart Rate; Hemorrhage; Male; Medulla Oblongata; Microinjections; Naloxone; Nervous System; Nervous System Physiological Phenomena; Rabbits

We measured changes in plasma renin activity (PRA) and used angiotensin-converting enzyme blockade with captopril to evaluate the role of the renin-angiotensin system during hemorrhage and after opioid receptor blockade in conscious rabbits. The increase in PRA after nonhypotensive hemorrhage was not statistically significant. PRA increased sixfold after a hypotensive hemorrhage to a mean arterial pressure less than 40 mmHg. This increase was statistically significant. Captopril altered the hemodynamic response to hemorrhage. The normal increase in vascular resistance early in hemorrhage was reduced by captopril pretreatment. After a critical blood loss, arterial pressure and heart rate decreased in both groups. The blood loss required to decrease mean arterial pressure to less than 40 mmHg was approximately 25% less in animals pretreated with captopril. The characteristic decrease in vascular resistance coincident with the onset of hypotension was still present after captopril pretreatment. Injection of naloxone or saline during acute hemorrhagic hypotension did not affect PRA. However, recovery of blood pressure after naloxone or saline was attenuated by converting-enzyme blockade. This attenuation was due primarily to a reduction in spontaneous recovery (i.e., recovery after the control saline injection) and not to a reduction in the response to naloxone. We tested whether this effect of captopril might be due to an interaction of ANG II and catecholamines. The plasma norepinephrine (NE) response to naloxone was statistically similar with and without captopril. In contrast, the response to exogenous NE after hypotensive hemorrhage was significantly reduced by captopril pretreatment. Captopril apparently did not alter baroreflex sensitivity but did reset the baroreflex to lower pressure levels during naloxone's pressor response.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Captopril; Endorphins; Hemodynamics; Hemorrhage; Male; Naloxone; Peptidyl-Dipeptidase A; Rabbits; Receptors, Opioid; Renin; Renin-Angiotensin System; Sodium Chloride; Sympathetic Nervous System; Synaptic Transmission

1. Cardiac output, arterial pressure, heart rate, systemic vascular conductance, respiratory rate and arterial blood PO2 and PCO2 were measured in unanaesthetized rabbits. Haemorrhage was simulated by inflating a cuff placed around the inferior vena cava so that cardiac output fell at a constant rate of about 8% of its resting value per min. 2. The effects of drug treatments on resting haemodynamic and respiratory variables, and on the haemodynamic response to simulated haemorrhage, were tested. The treatments were; 4th ventricular (-)-naloxone HCl (10-100 nmol), 4th ventricular H-Tyr-D-Ala-Gly-MePhe-NH(CH2)2OH (DAMGO; 30-300 pmol), and i.v. morphine sulphate (0.5-5.0 mumol kg-1). The interactions of graded 4th ventricular doses of naloxone (3-100 nmol) with the actions of DAMGO (100-300 pmol) on these responses were also assessed. 3. After sham treatments, the circulatory response to simulated haemorrhage had two phases. During the first compensatory phase, systemic vascular conductance fell, heart rate rose, and mean arterial pressure fell by only about 7 mmHg. A second decompensatory phase supervened when cardiac output had fallen by about 50%. At this point systemic vascular conductance rose abruptly and arterial pressure fell to less than or equal to 40 mmHg. 4. Low 4th ventricular doses of naloxone (10-30 nmol) and DAMGO (30-100 pmol) had no discernible effect on the circulatory response to simulated haemorrhage. Higher doses of naloxone (30-100 nmol) and DAMGO (100-300 pmol) prevented the decompensatory phase. These high doses of naloxone and DAMGO lowered resting heart rate without affecting the other haemodynamic or respiratory variables. 5. Low doses of i.v. morphine (0.5-1.Spumolkg-1) also had no discernible effect on the circulatory response to simulated haemorrhage. Higher doses of morphine (1.5-5.Opmol kg 1) abolished the decompensatory phase. These high doses caused respiratory depression without affecting the resting haemodynamic variables. 6. The prevention of circulatory decompensation by high doses of DAMGO was reversed by 3-10nmol of naloxone in 3 out of 4 rabbits and by 10-30 nmol of naloxone in all 4 rabbits. The decompensatory phase was, however, prevented by the combined high doses of DAMGO (100-300pmol) and naloxone (30-100 nmol). 7. These findings provide strong evidence that activation of mu-opioid receptors in the central nervous system abolishes circulatory decompensation during acute reduction of central blood volume in consc

Topics: Animals; Blood Gas Analysis; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Enkephalins; Hematocrit; Hemodynamics; Hemorrhage; Injections, Intraventricular; Morphine; Naloxone; Narcotics; Rabbits; Receptors, Opioid; Receptors, Opioid, mu; Respiration

Evidence that sympathetic outflow to organs with different functions reacts nonuniformly to various stimuli has accumulated. To clarify the difference in outflow characteristics of adrenal and renal nerves, the neural and neurochemical mechanisms involved in the response to hemorrhage were examined in anesthetized rats. Hemorrhage (2, 5, and 10 ml/kg) increased adrenal nerve activity (ANA) and decreased renal nerve activity (RNA) in a bleeding volume-dependent manner, accompanied with a decrease in mean arterial blood pressure and heart rate. Bilateral vagotomy attenuated the response in ANA and completely abolished the response in RNA. Sinoaortic denervation (SAD) and vagotomy combined with SAD inversely decreased ANA during hemorrhage. However, SAD appears to have no effect on the response in RNA, which was completely abolished by combined denervation. Our results suggest that the differential effects of hemorrhage on ANA and RNA may be due to different contributions via the afferent neural pathways from the baro- and cardiopulmonary receptors. Because naloxone attenuated the dissociated response to hemorrhage, the endogenous opioid system may be involved.

Topics: Acute Disease; Adrenal Glands; Adrenal Medulla; Anesthesia; Animals; Cardiovascular System; Denervation; Hemorrhage; Kidney; Male; Naloxone; Nervous System Physiological Phenomena; Rats; Rats, Inbred Strains; Sinus of Valsalva; Sympathetic Nervous System; Vagotomy

Experiments were conducted to determine (i) how naloxone administration alone could modify the inotropic (in electrically stimulated (ES) rat atria) and both the inotropic and chronotropic responses (in spontaneously beating (SB) rat atria) isolated from normotensive and hypotensive (hemorrhaged) rats, and (ii) how naloxone administration would modify the inotropic and chronotropic responses of isolated rat atria previously administered an opiate agonist (morphine), a muscarinic agonist (carbachol), or an alpha- and beta-adrenergic agonist (noradrenaline). Naloxone (51-340 microM) added to ES atria caused a delayed but dose-related decrease in atrial tension (AT), whereas in SB atria, naloxone caused atrial heart rate (AHR) to fall and atrial tension (AT) to increase. Naloxone (68-340 microM), given to SB atria from acutely hypotensive rats, caused a similar increase in atrial tension as seen in the "normotensive" isolated (SB) atria and a similar decrease in atrial heart rate. Morphine sulphate (MS), 37-375 microM, administered to ES atria caused a delayed fall in AT; which was further decreased when naloxone (340 microM) was also added. In the SB atria, morphine caused a dose-related decrease in atrial heart rate whereas atrial tension increased. In SB preparations, atrial heart rate fell even further when naloxone was added to morphine compared with when morphine sulphate was given alone, whereas atrial tension was increased. Noradrenaline (3 or 12 microM) caused a positive, dose-related inotropic response in the ES atria, effects not influenced by the addition of naloxone. In the SB atria, naloxone caused no change in the dose-related increases in atrial tension and heart rate when combined with the lower dose of noradrenaline but decreased AT when combined with 12 microM noradrenaline, compared with when this dose of noradrenaline was given alone. Carbachol (683 nM-1.37 microM) caused a dose-related decrease in atrial tension in ES atria, which was reversed completely by the addition of naloxone. In SB atria, carbachol decreased both atrial tension and heart rate, and with the addition of naloxone (340 microM), a further slight drop in atrial heart rate occurred, but concurrently, a marked rise in atrial tension was observed. The results indicate that naloxone can act with receptors directly within atrial tissue to cause changes in atrial tension and heart rate. The comparable delayed responses of morphine and naloxone suggest their effects are media

Topics: Animals; Carbachol; Electric Stimulation; Heart; Heart Rate; Hemorrhage; In Vitro Techniques; Male; Morphine; Myocardial Contraction; Naloxone; Norepinephrine; Rats; Rats, Inbred Strains

Topics: Animals; Blood Pressure; Brain Death; Dogs; Female; Hemorrhage; Kidney; Kidney Transplantation; Male; Naloxone

1. In unanaesthetized rabbits, haemorrhage was simulated by inflating a cuff placed round the inferior vena cava so that cardiac output fell at a constant rate of approximately 8% of its resting value per minute. The circulatory responses were measured after injections into the fourth ventricle of saline vehicle, selective opioid antagonists, selective opioid agonists, and agonist-antagonist mixtures. Three sets of experiments were done to determine if a specific subtype of opiate receptor within the central nervous system is responsible for the circulatory decompensation that occurs during simulated haemorrhage. 2. In six rabbits the effects of ascending doses of the antagonists naloxone (mu-selective), Mr 2266 (kappa- and mu-selective), ICI 174864 (delta-selective) and nor-binaltorphimine (kappa-selective) were tested. In three rabbits the effects of the antagonist naloxone, the agonists HTyr-D-Ala-Gly-MePhe-NH(CH2)2OH (DAGO, mu-selective), U 50488H (kappa-selective), and [D-Pen2,D-Pen5]-enkephalin (DPDPE, delta-selective), and combinations of these agonists with naloxone were tested. In four rabbits the dose-related effects of DAGO on respiratory, as well as circulatory, functions were examined. 3. After injecting saline vehicle, the circulatory response to simulated haemorrhage had two phases. During the first phase, systemic vascular conductance fell, heart rate rose, and mean arterial pressure fell by only approximately 10 mmHg. A second, decompensatory, phase began when cardiac output had fallen to approximately 50% of its resting level. At this point, there was an abrupt rise in systemic vascular conductance and a fall in mean arterial pressure to less than or equal to 40 mmHg. 4. The lower range of doses of naloxone (3-30 nmol), Mr 2266 (10-100 nmol), ICI 174864 (10-30 nmol), and all doses of nor-binaltorphimine (1-100 nmol), were without effect on the circulatory response to stimulated haemorrhage. Higher doses of naloxone (30-100 nmol), Mr 2266 (100-300 nmol) and ICI 174864 (30-100 nmol) abolished the decompensatory phase. The relative order of antagonist potency was ICI 174864 greater than or equal to naloxone greater than Mr 2266 greater than or equal to nor-binaltorphimine. 5. In the second set of experiments, the critical dose of naloxone necessary to prevent circulatory decompensation during simulated haemorrhage was 30-150 nmol. The delta-agonist DPDPE (50 nmol) did not affect the haemodynamic response to simulated haemorrhage, but it did

Topics: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Animals; Benzomorphans; Blood Circulation; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Enkephalin, D-Penicillamine (2,5)-; Enkephalin, Leucine; Enkephalins; Hemodynamics; Hemorrhage; Naloxone; Naltrexone; Narcotic Antagonists; Pyrrolidines; Rabbits; Receptors, Opioid; Vena Cava, Inferior

The present study investigated the question of whether peripheral or central opiate receptors are activated during controlled haemorrhagic hypotension. In anaesthetized Wistar rats, blood pressure was reduced by steps, by bleeding, to 80, 60 and 40 mmHg. Subcutaneous administration of 1 mg/kg of naloxone and of methyl naloxone-Br, an analogue of naloxone, which does not readily cross the blood-brain barrier, significantly elevated the bleeding volume at the 40-mmHg blood pressure level. A dose of 10 mg/kg of methyl naloxone-Br had no effect on the bleeding volume. We therefore conclude that during haemorrhage, endogenous opioid peptides activate both central and peripheral opiate receptors, thereby exerting a hypotensive influence.

Topics: Animals; Central Nervous System; Hemorrhage; Hypotension; Male; Naloxone; Oxymorphone; Peripheral Nerves; Rats; Rats, Inbred Strains; Receptors, Opioid

1. Acute haemorrhage was simulated in five unanaesthetized rabbits, by inflating a cuff on the inferior vena cava so that cardiac output fell by 8.3% of its resting level per minute. Simulated haemorrhage was performed after sham treatment, after graded doses of intravenous and intracisternal naloxone, and after cardiac nerve blockade with intrapericardial procaine. 2. After sham treatment, the haemodynamic response to simulated haemorrhage was biphasic. During the first phase, systemic vascular conductance fell steadily, heart rate rose steadily, and arterial pressure fell only slightly. A second decompensatory phase began abruptly when cardiac output had fallen to approximately 55% of its resting level. Vascular conductance rose steeply, heart rate fell slowly, and arterial pressure fell precipitately. 3. Treatment with naloxone (intravenous, 0.04-0.4 mg kg-1; intracisternal, 0.2-2 micrograms kg-1) did not affect either phase of the haemodynamic response to simulated haemorrhage. 4. After treatment with larger doses of naloxone (intravenous, 4-8 mg kg-1; intracisternal, 4-69 micrograms kg-1), the first phase was unaffected, but the second phase no longer occurred. Throughout simulated haemorrhage, systemic vascular conductance fell steadily, heart rate rose, and arterial pressure was well maintained. The dose of intracisternal naloxone which prevented the second phase was 90-900 times less than the corresponding intravenous dose. The second phase was also prevented by cardiac nerve blockade. 5. We conclude that an endogenous opiate mechanism is responsible for the haemodynamic decompensation that occurs when cardiac output falls to a critical level. The mechanism is located within the central nervous system. It is triggered by a signal from the heart.

Topics: Acute Disease; Animals; Atenolol; Central Nervous System; Cisterna Magna; Heart; Hemodynamics; Hemorrhage; Injections; Injections, Intraventricular; Naloxone; Nerve Block; Parasympatholytics; Pericardium; Procaine; Rabbits

Using the method of contact luminescent biomicroscopy of the liver and the intestine coupled with the ultrasonic measurement of systemic blood pressure, blood flow velocity in the portal vein and hepatic artery it has been established that in rats with acute decompensatory hemorrhage naloxone increases blood pressure and improves the state of protal macro and microcirculation only after i. v. injection of large dose (5 mg/kg). Naloxone does not influence the dynamics of acute compensatory hemorrhage and the development of the posthemorrhagic microcirculatory disturbances (local microstases, microthromboses, erythrocyte aggregation).

Topics: Acute Disease; Animals; Blood Circulation; Blood Pressure; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Hemorrhage; Male; Naloxone; Portal System; Rats; Rats, Inbred Strains

Effects of hemorrhage on renal nerve activity and of subsequent opiate receptor blockade with naloxone were studied in conscious rabbits. Mean arterial pressure remained constant at 77 +/- 2 mm Hg through 17 +/- 2 ml/kg hemorrhage, while renal nerve activity increased by 159 +/- 16%. After 25 +/- 1 ml/kg hemorrhage, mean arterial pressure fell by 42 +/- 3 mm Hg, and renal nerve activity decreased below the prehemorrhagic control level by 41 +/- 15%. Bolus injection of naloxone (3 mg/kg i.v.) increased mean arterial pressure to 79 +/- 2 mm Hg, not significantly different from the prehemorrhagic control level. Renal nerve activity increased by 171 +/- 28%, comparable to the peak increase during nonhypotensive hemorrhage. On a different day, hemorrhage was repeated, and phenylephrine was infused during the subsequent hypotension. Phenylephrine increased mean arterial pressure to the prehemorrhagic control level. With increasing mean arterial pressure, renal nerve activity increased from its level during hypotensive hemorrhage and recovered toward the prehemorrhagic control level (-26 +/- 11%), but it did not return to the peak value reached during nonhypotensive hemorrhage. To further examine the blocking effects of naloxone on changes in mean arterial pressure and renal nerve activity induced by exogenous opiate peptides, methionine-enkephalin was injected both in the control state and after treatment with naloxone. A bolus injection of methionine-enkephalin (10 micrograms/kg) decreased mean arterial pressure (-8.1 +/- 2.0 mm Hg) and renal nerve activity (-95 +/- 1%). Pretreatment with naloxone (0.5 mg/kg) effectively blocked this depressor effect and reduction in renal nerve activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Consciousness; Enkephalins; Hemorrhage; Hypotension; Kidney; Naloxone; Rabbits; Receptors, Opioid; Sympathetic Nervous System

The effects of enkephalin derivates with different opioid receptor subtype specificity and naloxone on cardiovascular responses and kallikrein-kinin system (KKS) were studied in anesthetized rats exposed to 30% hemorrhage. Administration of a mu-receptor agonist (DAGO) in early hemorrhage improved mean arterial blood pressure (MAP) responses to hemorrhage. This effect could be abolished by naloxone pretreatment. Moreover, a delayed MAP recovery after hemorrhage could be observed. Treatment with a delta-agonist (DADL) resulted in transient depression of MAP and heart rate (HR). Hemorrhage by itself caused only a slight activation of KKS as indicated by decreased plasma kallikreinogen concentration and reduced kallikrein inhibitor capacity after 20% blood loss. Enkephalin administration did not exert significant effects on KKS. Naloxone pretreatment, in contrast, induced prehemorrhagic activation of KKS, which was potentiated by subsequent hemorrhage. Naloxone-induced activation of KKS could be confirmed by an in vitro study. Taken together these results suggest that the KKS is not involved in MAP and HR responses to enkephalin administration during hemorrhage, whereas it might be implicated in naloxone-induced delayed posthemorrhagic MAP recovery.

Topics: Animals; Blood Pressure; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Enkephalin, Leucine; Enkephalin, Leucine-2-Alanine; Enkephalins; Hemorrhage; Injections, Intravenous; Kallikreins; Kinins; Male; Naloxone; Rats; Rats, Inbred Strains; Shock, Hemorrhagic

1. We investigated the effects of the opiate antagonist naloxone on changes in renal nerve activity and the renal sympathetic baroreflex during haemorrhage and whether they could be mimicked by blocking afferent input from cardiac receptors. 2. Renal nerve activity, arterial pressure and heart rate were recorded in conscious rabbits during blood loss of either 18 or 34-40% of the blood volume. The renal sympathetic baroreflex was elicited by perivascular balloon-induced changes in arterial pressure, before and at the end of haemorrhage. The experiment was repeated during intravenous naloxone infusion (4 mg kg-1, then 0.12 mg kg-1 min-1), and after blocking afferent input from cardiac receptors (5% intra-pericardial procaine). 3. Moderate haemorrhage elicited a rise in renal nerve activity and modest inhibition of the range of the renal sympathetic baroreflex. Severe haemorrhage triggered an abrupt fall in nerve activity and arterial pressure which was accompanied by strong inhibition of the baroreflex range and other curve parameters. There were minimal changes in the baroreceptor-heart rate reflex. 4. Intravenous naloxone and pericardial procaine prevented the falls in renal nerve activity and pressure triggered by severe blood loss but did not affect the increase in activity elicited by moderate haemorrhage. Both drugs produced similar enhancement of the normovolaemic renal sympathetic baroreflex. Naloxone prevented the baroreflex inhibition elicited by both levels of haemorrhage while pericardial procaine prevented most (but not all) of the baroreflex inhibition seen during severe haemorrhage without affecting that found during moderate haemorrhage. 5. We conclude that cardiac receptors (probably ventricular baroreceptors) but not arterial baroreceptors have an opiate synapse on their reflex pathways to the renal nerve. A major part of the action of naloxone during haemorrhage can be explained by blockade of this type of synapse on baroreflex pathways to renal and probably other sympathetic vasoconstrictors. The presence of procaine-resistant but naloxone-sensitive effects during haemorrhage suggests a role for extra-cardiac baroreceptors with opioid central nervous connections.

Topics: Action Potentials; Animals; Blood Pressure; Blood Volume; Heart Rate; Hemorrhage; Kidney; Naloxone; Pressoreceptors; Procaine; Rabbits; Reflex; Sympathetic Nervous System

We tested the hypothesis that enkephalins or some other compound(s) released by the adrenal medulla during hemorrhage were responsible for the resultant hypotension. We compared the hemodynamic and plasma catecholamine responses to hemorrhage and subsequent opioid receptor blockade with naloxone in intact, adrenal-denervated (ADD), and adrenalectomized (ADX) rabbits. The studies were done in conscious, chronically prepared, male New Zealand White rabbits. The hemodynamic response to hemorrhage was not different among the three groups. Plasma norepinephrine (NE) increased early in hemorrhage in all groups. In the ADD and ADX animals, NE decreased significantly at the transition to hypotension, suggesting decreased release of NE by peripheral sympathetic nerves as a possible cause of the decrease in pressure. In the intact group, NE did not decrease but reached a plateau possibly due to the release of some NE by the adrenal medulla, which obscured the decreased release by sympathetic nerves. The pressor response to naloxone, though present in all groups, was attenuated by adrenalectomy or adrenal denervation. The plasma NE response to naloxone was similar in all groups and involved a two- to threefold increase after naloxone. We conclude that enkephalins or any other compounds released by the adrenal gland are not responsible for the acute hemodynamic changes during hemorrhage in the conscious rabbit. However, some substance(s) released by the adrenal medulla, perhaps epinephrine, does play a role in naloxone's pressor effect, since this is reduced by adrenalectomy or adrenal denervation.

Topics: Adrenal Medulla; Adrenalectomy; Animals; Epinephrine; Hemodynamics; Hemorrhage; Male; Naloxone; Norepinephrine; Rabbits; Sodium Chloride; Time Factors

1. We have tested the hypothesis that the pressor action of (-) naloxone HC1 after haemorrhage is due to antagonism of endogenous opiate mechanisms that are activated by haemorrhage, rather than to some more direct vasoconstrictor action of the drug. 2. Six conscious rabbits were treated intravenously with either naloxone (4 mg kg-1, then 0.1 mg kg-1 min-1) or equivalent volumes of saline. In unbled rabbits the naloxone regimen had no effect except to cause a transient bradycardia. After each treatment the rabbits were bled at a rate of 2.45 ml kg-1 min-1 until blood pressure fell to 40 mmHg or 28 ml kg-1 of blood had been withdrawn (17-24 ml kg-1 after saline, 21-28 ml kg-1 after naloxone). 3. Throughout both episodes of bleeding there was a progressive fall of cardiac output and rise of heart rate, at rates that were constant and independent of the prior treatment. 4. After saline treatment, bleeding at first resulted in a steep and progressive fall of systemic vascular conductance and a small fall in blood pressure. However, when blood loss exceeded 12.7 ml kg-1 (approximately 28% of blood volume) there was an abrupt rise in systemic vascular conductance and an abrupt fall in blood pressure. 5. After naloxone treatment, during the entire period of bleeding systemic vascular conductance fell steeply and blood pressure fell slowly. 6. The different effects of saline and naloxone on the haemodynamic responses to acute blood loss were not explicable by differences in haematocrit or net blood volume. 7. We conclude that endogenous opiate mechanisms are responsible for the abrupt vasodilation that occurs when more than 28% of blood volume is withdrawn rapidly from conscious rabbits. We suggest that these mechanisms reside in the central nervous system.

Topics: Acute Disease; Animals; Blood Pressure; Blood Volume; Body Weight; Heart Rate; Hematocrit; Hemodynamics; Hemorrhage; Naloxone; Rabbits; Sodium Chloride; Vascular Resistance

Naloxone reverses hemorrhagic hypotension in the conscious guinea-pig. Captopril and saralasin impede this naloxone effect, suggesting that angiotensin II is involved in naloxone action. This is compatible with previous work which has shown that B-endorphin inhibits the centrally mediated pressor action of angiotensin II, and that naloxone blocks this effect. Naloxone may be interacting with the postulated brain renin-angiotension II system or may be blocking the action of shock-induced circulating angiotensin II on a centrally located area such as the hypothalamus.

Topics: Animals; Blood Pressure; Captopril; Guinea Pigs; Hemorrhage; Hypotension; Hypothalamus; Naloxone; Neural Inhibition; Receptors, Opioid; Renin-Angiotensin System; Saralasin

There is new evidence from experiments in conscious animals that when acute blood loss exceeds about 30% of blood volume, reflex vasoconstriction is abruptly replaced by widespread vasodilatation, and there is a precipitous fall in arterial blood pressure. This vasodilatation is associated with a decline in sympathetic vasoconstrictor drive. It is likely that the signal which causes the switch from vasoconstriction to vasodilatation reaches the brain via afferent nerves from the heart. There is also circumstantial evidence that endogenous opiate mechanisms are involved in the translation of the cardiac afferent signal into failure of reflex sympathetic vasoconstrictor drive. These mechanisms may explain the 'vaso-vagal' reaction that can occur in man during or following acute, severe, blood loss.

Topics: Animals; Hemorrhage; Humans; Naloxone; Receptors, Cell Surface; Reflex; Vascular Resistance; Vasoconstriction; Vasodilation

We have analyzed the efferent mechanisms responsible for the bradycardia that occurs when naloxone (6 mg/kg) is given i.v. to conscious rabbits after acute blood loss of 17-20 ml/kg. Atenolol and hyoscine methyl bromide were given intrapericardially (i.p.c.), singly and in combination, to allow factorial analysis of the contributions of sympathoadrenal beta-adrenergic and vagal cholinergic mechanisms. In addition, the effects of ganglion blockade with mecamylamine on the heart rate response to naloxone, and of i.p.c. naloxone on the cardiac pacemaker, were tested. The treatments had little effect on the pressor response to naloxone. Central nervous mechanisms were responsible for most of the bradycardia of approximately 160 beats/min evoked by naloxone in sham-treated, bled, rabbits. Increased vagal drive accounted for one-half the response, withdrawal of sympathoadrenal drive for 20%, and there was no significant interaction. These effects appeared to be due to evocation of a baroreceptor-heart rate reflex by the concomitant rise in blood pressure. Non-cholinergic, non-adrenergic mechanisms were responsible for a fall in heart rate of approximately 35 beats/min, part of which was due to a direct action of naloxone on the cardiac pacemaker.

Topics: Animals; Atenolol; Blood Pressure; Bradycardia; Ganglionic Blockers; Heart Rate; Hemorrhage; N-Methylscopolamine; Naloxone; Pericardium; Pressoreceptors; Rabbits; Scopolamine Derivatives; Sympathectomy, Chemical

The role of the brain opioid system in the control of hypothalamic-pituitary-adrenal activity was studied in 10 conscious sheep with an indwelling cannula in a cerebral lateral ventricle. On separate days, sheep received infusions of artificial CSF (control) and the opiate antagonist, naloxone (100 micrograms/hr) before and during acute moderate hemorrhage (15 ml/kg over 10 min). Infusion of naloxone before hemorrhage raised plasma ACTH and resulted in a significant increase in cortisol compared to the control infusion. In contrast, ACTH and cortisol responses to hemorrhage tended to be blunted by central naloxone infusion. The responses of vasopressin, aldosterone and the catecholamines remained unaffected by naloxone. The fall in blood pressure and the rise in heart rate accompanying hemorrhage were likewise unaltered. These results suggest that brain opioid peptides have an inhibitory effect on basal ACTH secretion but do not play a major role in modulating the hemodynamic or pituitary-adrenal responses to acute moderate hemorrhage in conscious sheep.

Topics: Adrenocorticotropic Hormone; Aldosterone; Animals; Arginine Vasopressin; Blood Pressure; Cerebral Ventricles; Epinephrine; Female; Heart Rate; Hemorrhage; Hydrocortisone; Injections, Intraventricular; Kinetics; Naloxone; Norepinephrine; Sheep

Concurrent levels of methionine-enkephalin and catecholamines in adrenal vein, femoral vein and femoral artery were measured under baseline conditions and during graded hemorrhage in halothane anesthetized dogs and compared to a non-bled control group. Naloxone was administered in both groups at the end of the experiment. Normotensive hypovolemia with a remaining blood volume of 76% led to a moderate decrease in mean arterial blood pressure from baseline and a 15- to 20-fold increase in norepinephrine, epinephrine and dopamine, and a 5-fold increase in enkephalin in the adrenal vein. Subsequent induction of hypotensive hypovolemia with a remaining blood volume of 51% resulted in a profound drop in blood pressure and evoked a further increase in the level of catecholamines (40- to 50-fold from baseline) and enkephalin (8-fold from baseline) in the adrenal vein. In the control group only a 3- to 4-fold increase from baseline in adrenal vein hormone levels was observed over time. Naloxone administration at the end of the experiment, led to a 2- to 6-fold further increase in hormones at the 3 collection sites in both groups of dogs. Joint calculation of the partial correlation coefficients for the influence of preceding blood volume and blood pressure, and concurrent blood volume and blood pressure on hormone secretion in the adrenal vein revealed that these variables explained the variation in hormone levels between 56 and 92% during normotensive hypovolemia and 62-83% during hypotensive hypovolemia. In one dog with bilateral adrenalectomy, hemorrhage was poorly tolerated, and naloxone administration did not lead to increased systemic plasma levels of catecholamines and enkephalin or improved hemodynamics. In the hemorrhage group, molar ratios of norepinephrine/epinephrine in the adrenal vein showed a significant increasing trend during the experiment. Findings in these experiments support the idea of differential monoaminergic and enkephalinergic regulation in adrenal medullary cells.

Topics: Adrenal Glands; Animals; Blood Pressure; Catecholamines; Dogs; Dopamine; Enkephalin, Methionine; Epinephrine; Female; Halothane; Heart Rate; Hemorrhage; Kinetics; Male; Naloxone; Norepinephrine; Reference Values

The purpose of the study was to examine the effects of naloxone on signs of cerebral ischaemia during hypotensive haemorrhage in unanaesthetized spontaneously hypertensive rats. Mean arterial blood pressure (MAP), heart rate (HR) and somatosensory evoked potentials (SEP) were recorded. Arousal tests were also performed and the behavioural responses quantified. The SEP alone were a poor indicator of cerebral function in these unanaesthetized rats, because they were markedly influenced by changes in activity and arousal of the animals. Hypotensive haemorrhage resulted in a biphasic tachycardia response, an attenuation of the first SEP component and a reduction of the behavioural response score. Naloxone, 5 mg kg-1 i.v., induced transient bradycardia and a dramatic improvement in arousal test responses, while SEP were not clearly altered. The MAP was kept constant after naloxone injection by adjustments of bleeding and transfusion. Injection of naloxone in unbled control SHR also induced bradycardia but without any changes in SEP and the behavioural responses. The results indicate that naloxone can have beneficial effects in cerebral ischaemia. Possible mechanisms are discussed.

Topics: Animals; Arousal; Behavior, Animal; Brain Ischemia; Depression; Evoked Potentials, Somatosensory; Hemodynamics; Hemorrhage; Hypotension; Male; Naloxone; Rats; Rats, Inbred SHR

Overhydration inhibits release of vasopressin (VP) and oxytocin (OT) from the hypothalamo-neurohypophysial system during hypovolemia. We investigated whether opioid peptides mediate the inhibitory effect of water on secretion of these hormones. Conscious male rats were made hypovolemic by hemorrhage (HEM, 0.51 ml/min) of 20 and 35% of the blood volume or by injection of either subcutaneous polyethylene glycol (PEG, 20,000 mol wt, 35 ml/kg) or intraperitoneal histamine (HIS, 15 mg/kg, 1 ml/kg). Animals were intubated orally 1-4 min (HEM, HIS) or 6.75 h (PEG) later with or without administration of water (40 ml/kg). Four to seven min after intubation rats were injected with saline (1 ml/kg) or naloxone (2 or 5 mg/kg) and then decapitated 6-10 min later. Control animals were treated similarly but were not stimulated by hypovolemia. VP and OT were extracted from plasma and quantified by radioimmunoassay. Data were analyzed by analysis of variance. In HEM animals blood pressure fell and plasma osmolality increased, both of which correlated positively with the rise in plasma [VP] and [OT]. Overhydration lowered the plasma osmolality, attenuated the fall in blood pressure, and reduced [VP] and [OT] in plasma of HEM animals. The opiate receptor antagonist, naloxone, did not alter these changes in blood pressure or plasma osmolality, or the plasma [VP] after HEM in rats treated with or without water. Plasma [OT] was, however, increased by naloxone in both normally hydrated and overhydrated rats. Thus, regardless of the hydrational state of the animal, opioid peptides inhibited release of OT but not VP during hemorrhage. Data consistent with this interpretation were also obtained from rats made hypovolemic with PEG or HIS.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Blood Volume; Cardiovascular System; Endorphins; Hemorrhage; Histamine; Male; Naloxone; Osmolar Concentration; Oxytocin; Polyethylene Glycols; Rats; Rats, Inbred Strains; Vasopressins; Water

Five rabbits were allotted to each of six treatments on a matched-individual basis. Treatments were none, sham, total adrenalectomy with adrenocorticoid replacement, intravenous guanethidine (15 mg X kg-1 X day-1), adrenalectomy + guanethidine, and adrenal medullectomy. The conscious rabbits were bled 20 ml/kg over 5 min. Naloxone (6 mg/kg) was injected intravenously. The responses of arterial pressure and of plasma epinephrine (E) and norepinephrine (NE) concentrations were measured. Factorial analysis was used to calculate the effects of sympathetic noradrenergic nerves (SYM) and the adrenal medulla (ADR) on the responses. In combination, SYM + ADR fully accounted for the pressor response observed in normal and sham-treated rabbits. SYM and ADR each made independent and approximately equal contributions to the response, but the SYM X ADR interaction was strongly antagonistic. The responses of plasma E and NE were fully accounted for by the adrenal glands and sympathetic nerves, respectively. The pressor responses after total adrenalectomy and adrenal medullectomy were similar. Thus hemorrhage-stimulated adrenal corticosteroid release was not essential to naloxone's action, and adrenal enkephalins were not responsible for naloxone's action on sympathetic pathways.

Topics: Adrenal Medulla; Adrenalectomy; Animals; Blood Pressure; Cardiovascular Physiological Phenomena; Cardiovascular System; Epinephrine; Guanethidine; Heart Rate; Hemorrhage; Hydrocortisone; Naloxone; Norepinephrine; Rabbits

The effects of continuous intravenous infusion of naloxone or vehicle on the blood pressure and vasopressin responses to step-wise hemorrhage were examined in conscious, age-matched spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto rats (WKY). Step-wise hemorrhage progressively lowered blood pressure and increased plasma vasopressin levels in both SHR and WKY. The WKY were relatively resistant to the hypotensive effect of hemorrhage. No significant differences were noted in blood pressure responses between naloxone-treated and vehicle-treated SHR while naloxone treatment attenuated hypotension only slightly in WKY. Plasma vasopressin levels were also elevated by naloxone treatment in SHR following a nonhypotensive hemorrhage equivalent to 0.5% of body weight. However, no differences were observed between plasma vasopressin levels in naloxone-treated and vehicle-treated SHR at greater degrees of hemorrhage. In addition, plasma vasopressin levels were similar at all times in hemorrhaged WKY, regardless of treatment. Plasma vasopressin levels were increased by naloxone in both time-control SHR and WKY. The data demonstrate that naloxone-sensitive systems exert only minimal effects on the immediate cardiovascular responses to hypovolemia in normotensive rats and no measurable effects in SHR. It does appear that naloxone-sensitive mechanisms contribute a small, but significant, tonic inhibitory influence over vasopressin secretion in both normotensive and hypertensive rats under basal conditions and in SHR in response to a small reduction in blood volume.

Topics: Animals; Blood; Blood Pressure; Heart Rate; Hemorrhage; Hypertension; Male; Naloxone; Osmolar Concentration; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Receptors, Opioid; Vasopressins

It has been reported that naloxone may be useful in the treatment of hypovolemic shock. However, the effects of naloxone on cardiac energy metabolism in acute hemorrhage have not been investigated. The effects of naloxone on myocardial metabolism were evaluated in the rat during acute hemorrhage with crystalloid resuscitation. Intramyocardial high energy phosphates, pyruvate, lactate and glycogen were measured. There was no significant difference in high energy phosphates, energy charge, lactate and glycogen contents between control, 1 mg naloxone and 10 mg naloxone groups. However, pyruvate level in hearts in the 10 mg naloxone group was significantly higher than that in control group. Therefore, naloxone reduced the lactate/pyruvate (L/P) ratio. Although naloxone did not improve the mitochondrial function, it improved the oxidation-reduction state in cardiac energy metabolism.

Topics: Animals; Energy Metabolism; Heart; Hemorrhage; Lactates; Lactic Acid; Male; Myocardium; Naloxone; Pyruvates; Rats; Rats, Inbred Strains

We investigated the mechanism for the pressor effect of intravenous administration of naloxone in pentobarbital-anesthetized cats. Comparisons were made between groups of hemorrhaged animals that received either naloxone or an equivalent volume of saline after 1 h of hemorrhage. Two other groups of hemorrhaged animals were depleted of serotonin by pretreatment with para-chlorophenylalanine 40-48 h before the experiment. One group of serotonin-depleted animals received naloxone after 60 min of hemorrhage and the other group received saline. Animals with normal brain serotonin content showed a significant pressor effect following naloxone when compared with animals given saline. Animals with reduced brain serotonin content also had a pressor response following naloxone administration. Serotonin-depleted animals showed an increase in maximum left ventricular dP/dt following naloxone administration when compared to serotonin-depleted animals given saline. Our data are consistent with the hypothesis that naloxone can exert a pressor effect in hemorrhaged cats by actions at central and at peripheral sites. In cats with normal serotonin values, the peripheral action of naloxone is predominant. In serotonin-depleted animals given naloxone, central and peripheral sites contribute to the pressor effect.

Topics: Animals; Blood Pressure; Brain Chemistry; Cats; Drug Interactions; Female; Hemodynamics; Hemorrhage; Intracranial Pressure; Naloxone; Neurons; Serotonin; Sympathetic Nervous System; Time Factors

The effect of trauma on human thermoregulation has been studied using a behavioural test and the vascular response to cold exposure. It was confirmed, in controls, that a pleasurable temperature for the hand (Thand) depended on core temperature (Tc) to which it was negatively related. Shortly after moderately severe fractures in a leg this relationship was lost and in the patients the slope of this regression line was not significantly different from zero and they usually chose a Thand towards the upper end of the normal range irrespective of Tc. This effect was not imitated in controls by removing 500 ml blood but Thand was increased by occluding the circulation to one leg. Naloxone did not alter Thand in controls but when given in a suitable dose it reduced the rise in Thand during a short period of limb ischaemia. Immersing one hand and forearm in water at 17 degrees C reduced the blood flow through the contralateral forearm and hand. The reduction in flow was positively related to the initial rate of flow in both controls and injured but the slope of the regression line was significantly less after injury. It is concluded that thermoregulation is affected by trauma in man.

Topics: Adolescent; Adult; Aged; Blood Vessels; Body Temperature; Body Temperature Regulation; Extremities; Female; Hand Injuries; Hemorrhage; Humans; Ischemia; Male; Middle Aged; Naloxone; Pleasure-Pain Principle; Wounds and Injuries

The effect of opiate antagonist therapy with naloxone on hemorrhagic shock was examined. An equivalent intravenous bolus of naloxone or normal saline had the same pressor effect in conscious, unrestrained, hypovolemic hypotensive rats. The proposal that opiate antagonists are of therapeutic value in the treatment of hemorrhage is questioned.

Topics: Animals; Blood Pressure; Hemorrhage; Hypotension; Male; Naloxone; Rats; Rats, Inbred Strains; Sodium Chloride

The circulatory responses to different intravenous doses of naloxone were studied in conscious rabbits before and after haemorrhage, under different conditions including prior ganglion blockade. Unless there had been blood loss, naloxone elicited no pressor response, even in high dose. After bleeding so that arterial pressure fell to 40 mmHg, the dose-response relationship for naloxone had two components. Over a low-dose range (threshold 0.3 mg/kg) naloxone had a modest pressor effect but did not affect heart rate. Over a much higher dose range (threshold 0.6 mg/kg) naloxone caused a marked rise in arterial pressure and a profound bradycardia. The highest dose of naloxone examined (25 mg/kg) caused a rise in arterial pressure of 70 mmHg and a reduction in heart rate of 160 beats/min. The pressor and bradycardic effects of naloxone were the same whether post-haemorrhagic hypotension lasted 5, 10, 20 or 30 min. The responses to naloxone in low or high dose depended much more closely on the volume of blood removed than on the level to which arterial pressure fell. Even after non-hypotensive haemorrhage a high dose of naloxone had marked pressor and bradycardic effects. Ganglion blockade prior to haemorrhage abolished the pressor response to a low, but not to a high, dose of naloxone. It was concluded that prolonged and severe hypotension are not necessary to 'prime' the cardiovascular system to respond to naloxone after haemorrhage. In a high dose its pressor effects appear to be mediated post-ganglionically, but in a low dose it may act within the central nervous system.

Topics: Animals; Blood Pressure; Dose-Response Relationship, Drug; Epinephrine; Heart Rate; Hemorrhage; Mecamylamine; Naloxone; Norepinephrine; Rabbits

The hemodynamic and plasma catecholamine response to hypotensive hemorrhage and subsequent opioid receptor blockade with naloxone were evaluated before and after complete sinoaortic denervation (SAD). This study was done to test the general hypothesis that opioid-mediated failure of the baroreflex accounts for the hypotension of hemorrhage. The specific hypothesis we tested was that SAD would abolish the pressor effect of opioid receptor blockade with naloxone. The studies were done in conscious chronically prepared rabbits. Hemorrhage of 12 ml/kg did not change mean arterial blood pressure in intact animals due to a compensatory increase in heart rate and vascular resistance. When blood loss exceeded 12 ml/kg, pressure decreased abruptly due to a decrease in vascular resistance. Plasma norepinephrine (NE) and epinephrine (E) were higher after hemorrhage than before. Plasma E levels increased almost 70 times. After SAD, mean blood pressure began to decrease at the beginning of hemorrhage, the heart rate increase was abolished, and vascular resistance decreased throughout the blood loss. Plasma NE was no different after hemorrhage than before. Plasma E increased, but the increase was only fivefold. Naloxone increased mean arterial blood pressure, vascular resistance, cardiac index, and plasma NE before and after SAD. The increases in blood pressure and plasma norepinephrine were significantly greater after SAD. Therefore the pressor effect of naloxone in this model is not due to increased baroreflex sensitivity. Rather, intact baroreflexes buffer naloxone's effects.

Topics: Animals; Aorta; Cardiovascular System; Carotid Sinus; Consciousness; Denervation; Hemorrhage; Male; Naloxone; Pressoreceptors; Rabbits

The purpose of this study was to examine the effects of naloxone on signs of relative cerebral ischaemia induced by hypotensive haemorrhage. Mean arterial blood pressure (MAP), heart rate (HR), renal sympathetic nerve activity (rSNA) and somatosensory evoked potentials (SEP) were recorded in chloralose-anaesthetized spontaneously hypertensive rats exposed to graded bleeding. Hypotensive haemorrhage resulted, after a very brief sympathetic excitation, in marked sympathetic inhibition and bradycardia and a considerable reduction of SEP, indicating relative cerebral ischaemia. However, after 25-30 min this sympatho-inhibitory response was reversed to pronounced sympathetic excitation and tachycardia, which was accompanied by a further attenuation of SEP. A single bolus of naloxone (10 mg kg-1) caused transient sympathetic inhibition and bradycardia, which was accompanied by an improvement of SEP. A bolus injection (5-10 mg kg-1) followed by a 30 min infusion of naloxone (25-35 mg kg-1 h-1) caused a sustained SEP improvement despite the fact that MAP was kept constant during naloxone administration. We conclude that naloxone can have beneficial effects on brain function during cerebral ischaemia, effects that are probably due to blockade of opioid receptors. Our model of relative cerebral ischaemia might be useful for evaluating the mechanisms behind the naloxone effects during this condition.

Topics: Animals; Blood Pressure; Brain; Brain Ischemia; Evoked Potentials, Somatosensory; Heart Rate; Hemorrhage; Hypotension; Male; Naloxone; Rats; Rats, Inbred SHR; Sympathetic Nervous System

The involvement of the sympathetic nervous system in the cardiovascular response to hemorrhage and subsequent opiate receptor blockade was studied in conscious rabbits. Plasma catecholamines were measured by high-pressure liquid chromatography to indirectly assess sympathetic activity. Arterial blood samples were drawn at four times during the experiment: 1) before hemorrhage; 2) after a 15% blood loss; 3) after mean arterial blood pressure decreased to less than 40 mm Hg; and 4) 2 min after an i.v. injection of naloxone (3 mg/kg) or saline. Rapid removal of 15% of the total blood volume (approximately equal to 8 ml/kg) increased heart rate and plasma norepinephrine. Plasma epinephrine and blood pressure remained at control levels. Further hemorrhage (approximately equal to 16 ml/kg) produced a sudden decrease in blood pressure and a large increase in plasma epinephrine. Plasma norepinephrine was not significantly different from the previous sample. Subsequent injection of naloxone significantly increased plasma norepinephrine and blood pressure compared to the saline-treated group. Plasma epinephrine was similar in the two groups. These studies suggest that naloxone may exert its pressor effect during hemorrhagic hypotension in the conscious rabbit by blocking a naturally occurring, opiate peptide-mediated inhibition of norepinephrine release. The results are consistent with a peptidergic limit on sympathetic activity being responsible for the decrease in blood pressure seen during acute hemorrhage.

Topics: Adrenal Medulla; Animals; Blood Pressure; Endorphins; Epinephrine; Heart Rate; Hemodynamics; Hemorrhage; Male; Naloxone; Norepinephrine; Rabbits; Vascular Resistance

Naloxone increases arterial pressure in hemorrhaged animals, but its effects on organ blood flows are not well established. We measured central and regional hemodynamics immediately before and 25 min or 55 min after hemorrhage in 33 anesthetized rats. Fifteen minutes after the beginning of hemorrhage, animals received either vehicle (n = 17) or naloxone (n = 16), 10 mg/kg, intravenously. At 25 min, animals treated with naloxone had a greater blood flow to the left cerebral hemisphere than those receiving vehicle, but all other measurements were similar. At 55 min, the mean arterial pressure and heart rate were greater in animals treated with naloxone, but blood flow was increased to the spleen only. Vascular resistance values were greater in the gastrointestinal tract and less in the spleen in animals receiving naloxone. The data confirmed that, in anesthetized rats, naloxone increased mean arterial pressure and splenic blood flow and transiently increased cerebral blood flow, but other regional flows and cardiac output were similar to those in rats receiving vehicle only.

Topics: Analysis of Variance; Animals; Blood Pressure; Cardiac Output; Cerebrovascular Circulation; Heart Rate; Hemodynamics; Hemorrhage; Male; Microspheres; Naloxone; Rats; Rats, Inbred Strains; Regional Blood Flow; Spleen; Time Factors; Vascular Resistance

Naloxone, an opiate antagonist, is reported to reverse hypotension and to improve survival in hemorrhaged and septic animals. We have found recently that naloxone also blunts the hyperglycemic response to hemorrhage. This could result from a naloxone-induced diminution of the hypotensive stimulus to hyperglycemia, from a naloxone-induced diminution of hormonal secretion or action, from a naloxone-mediated decrease in glucose production, or from a direct action of naloxone on glucose uptake in skeletal muscle and other peripheral tissues. In order to examine the direct effect of naloxone on glucose uptake in skeletal muscle, male Sprague-Dawley rats were perfused in a standardized isolated perfused hindlimb system with or without naloxone (0.5 microgram/ml of perfusate). No insulin was added to the perfusate. Glucose uptake in animals treated with naloxone was 30.2% greater than that of control animals (p less than 0.05). This increase was not dependent on insulin. Although no significant differences were noted in the individual products of glucose utilization, the total tissue glucose that could be accounted for by these intermediates was increased in naloxone-treated hindlimbs (p less than 0.05). Thus the increase in glucose uptake by skeletal muscle noted in these experiments may explain, in part, the blunted hyperglycemic response to hemorrhage that occurs after naloxone administration. These results also suggest the possibility that endogenous opiates may be important in regulating glucose metabolism after hemorrhage.

Topics: Animals; Glucose; Hemorrhage; Hindlimb; Hyperglycemia; Hypotension; Male; Naloxone; Perfusion; Rats; Rats, Inbred Strains

Sixteen anesthetized foxhounds were instrumented for hemodynamic measurements. The adrenolumbar vein was cannulated, and hemorrhagic hypotension (MAP = 40 mmHg for 3h) was induced by bleeding. The plasma levels of beta-endorphin (beta-END), methionine-enkephalin (M-ENK), and leucine-enkephalin (L-ENK) were determined in systemic and adrenal venous blood by specific RIA. Five dogs received an i.v. bolus of naloxone (2 mg/kg) and a subsequent naloxone infusion of 2 mg/kg per hour 1 h after onset of hypovolemia. Eleven dogs served as controls and received equivalent volumes (1 ml/kg per hour) of saline. Hemorrhage resulted in a sharp increase in plasma concentrations of all measured opioid peptides, particularly of M-ENK (26-fold) and L-ENK (24-fold) in the adrenal effluent. Systemic beta-END levels remained 3-fold increased, whereas the ENK release decreased spontaneously. Naloxone treatment inhibited the spontaneous fall of adrenal ENK release during the hypotensive phase; the ENK values remained elevated 20- to 35-fold. Reinfusion of the autologous blood resulted in a normalization of the concentrations of all peptides in both groups. These data demonstrate that hemorrhagic hypotension will cause stimulation of release of endogenous opioid peptides. The high levels of ENK in the adrenal effluent indicate that the adrenal gland is the main source of these peptides in the circulation. In addition to beta-END, the ENK have therefore to be considered as possible factors perpetuating circulatory shock.

Topics: Adrenal Glands; Animals; beta-Endorphin; Dogs; Endorphins; Enkephalin, Leucine; Enkephalin, Methionine; Female; Hemorrhage; Hypotension; Male; Naloxone

The central and peripheral hemodynamic effects of rapid hemorrhage and subsequent opiate receptor blockade were studied in conscious rabbits. With hemorrhage of less than 12 ml/kg, mean arterial blood pressure (BP) was maintained by an increase in total peripheral resistance (TPR). Cardiac output (CO) declined in spite of an increase in heart rate (HR). Blood loss greater than 13 ml/kg resulted in an abrupt decrease in BP that was largely due to a decline in TPR. CO continued to decline gradually as it did early in hemorrhage. HR also decreased at the transition to hypotension. Subsequent opiate receptor blockade with naloxone (3 mg/kg) produced a prompt increase in BP and a decrease in HR. An increase in TPR accounted for the rise in BP. CO did not change significantly after naloxone. Therefore the hypotension associated with hemorrhage results from a decline in peripheral vascular resistance that is reversible by opiate receptor blockade with naloxone. These results are consistent with the involvement of opiate receptors and endogenous opiate peptides centrally and/or peripherally in control of vascular resistance during acute hemorrhagic hypotension.

Topics: Animals; Consciousness; Hemodynamics; Hemorrhage; Hypotension; Male; Naloxone; Rabbits; Receptors, Opioid; Time Factors; Vascular Resistance

Experiments on 48 adult rats anesthetized with urethane were made to study the effects of naloxone and thyrotropin-releasing hormone on respiration after acute hemorrhage. The drugs were injected intravenously in doses 0.25-0.30 mg/kg. The changes found in the electromyogram of the diaphragm, blood pressure and ECG demonstrated naloxone and thyrotropin-releasing hormone to stimulate the respiratory center at different stages of respiratory disorders (dyspnea, apnea, gasping) induced by hemorrhage.

Topics: Acute Disease; Animals; Blood Pressure; Drug Evaluation, Preclinical; Electrocardiography; Electromyography; Hemorrhage; Hypoxia; Naloxone; Rats; Respiration; Stimulation, Chemical; Thyrotropin-Releasing Hormone

Awake rats were bled 2.5 per cent of their body weight during 15 min. This caused a 50-fold increase of plasma adrenaline and a 15-fold increase of plasma noradrenaline after 90 min. Treatment with naloxone or morphine did not significantly affect blood pressure or plasma catecholamine levels. The results suggest that the action of naloxone in hemorrhagic hypotension is not mediated via the sympatho-adrenal system.

Topics: Animals; Blood Pressure; Catecholamines; Dopamine; Epinephrine; Hemorrhage; Male; Morphine; Naloxone; Norepinephrine; Rats; Rats, Inbred Strains

To assess the role of endogenous opiates on the hormonal and cardiovascular responses to moderate hemorrhage (H) and/or nociceptor activation, naloxone (Nx; 100 micrograms/kg, iv) was given coincident with H (10 ml/kg), tooth pulp nerve stimulation (TP), or H plus TP in anesthetized cats. We have previously reported that TP potentiated the ACTH response to H. Nx treatment did not affect this TP potentiation of ACTH after H, nor did Nx affect the ACTH response to H alone. This suggested that the interaction between nociceptor and baroreceptor afferent nerves, which may underlie the observed TP potentiation of ACTH release after H in the anesthetized cat, was not dependent upon naloxone-sensitive opiate pathways. In contrast, Nx attenuated the fall in arterial pressure during H or H plus TP and completely blocked the normally observed hyperglycemia. Catecholamines showed a prompt rise during H or H plus TP in Nx-treated animals. Thus, altered adrenomedullary hormone release cannot account for the attenuated fall in blood pressure or the inhibition of hyperglycemia during H or H plus TP. Nx presented alone or in combination with TP did not significantly affect any measured variable. To determine if Nx acted directly at the level of the liver to block H-induced hyperglycemia, a second group of animals received intraportal injections of Nx (20, 50, or 100 micrograms/kg) before H. Nx did not block the rise in glucose after H, although each of the three doses of Nx significantly attenuated the early (at +1 min) fall in blood pressure. Portal venous samples of glucagon and insulin during H were not significantly affected by Nx. These results suggest that 1) naloxone-sensitive endogenous opiate receptors are not necessary for the rise in ACTH during H or for the TP potentiation of H-induced increases in ACTH; 2) the fall in mean arterial pressure and the rise in glucose during H are selectively attenuated by Nx independent of significant changes in peripheral catecholamine levels when compared to Nx untreated animals; and 3) finally, Nx does not act directly at the liver to block the H-induced rise in glucose, but, rather, is effectively cleared from the circulation by the liver.

Topics: Adrenocorticotropic Hormone; Animals; Blood Glucose; Blood Pressure; Catecholamines; Cats; Dental Pulp; Electric Stimulation; Female; Heart Rate; Hemorrhage; Male; Naloxone; Portal Vein

Naloxone or physiological solution were injected in different doses to 11 baboons (Papio hamadryas) weighing 7-8 kg after bloodletting in a volume of 40% of the total amount of the blood. Naloxone effectively raised (in all the doses) the arterial blood pressure which dropped after bloodletting. The action of naloxone injected in small doses was more pronounced and had unique time parameters. Besides, the respiratory rate was also increased. Injection of nalorphine in a dose of 1 mg/kg produced a similar but a more demonstrable action as compared with naloxone in a dose of 1 mg/kg. A conclusion is made about the possibility of using the antagonists of opioid peptides on a clinical basis for the treatment of shock conditions. An assumption of an inconclusive role played by the subtypes of opiate receptors in the formation of shock conditions is also confirmed.

Topics: Acute Disease; Animals; Blood Pressure; Hemorrhage; Hypotension; Male; Nalorphine; Naloxone; Papio; Respiration

1. The effects of naloxone on blood pressure recovery after either rapid arterial haemorrhage or prolonged venous haemorrhage were studied in rats lacking vasopressin (Brattleboro strain) and in control (Long Evans) rats. 2. To produce similar reductions in blood pressure, less blood had to be taken from the Brattleboro rats than from the Long Evans rats. 3. After rapid arterial haemorrhage in the absence of naloxone, blood pressure recovery was slower in Brattleboro rats than in Long Evans rats. Naloxone did not affect the response to rapid arterial haemorrhage in Long Evans rats, but improved blood pressure recovery in Brattleboro rats; despite this improvement, the Brattleboro rats remained hypotensive at a time when the Long Evans rats were normotensive. These findings suggest that both the absence of vasopressin and a depressor action of beta-endorphins may contribute to the poor ability of Brattleboro rats to cope with rapid haemorrhage. 4. After prolonged venous haemorrhage in the absence of naloxone, there was no difference between the recovery of blood pressure in Brattleboro rats and Long Evans rats. Naloxone improved blood pressure recovery to a similar extent in both strains of rat. These findings suggest that the absence of vasopressin does not impair blood pressure recovery after prolonged haemorrhage.

Topics: Animals; Blood Pressure; Heart Rate; Hemorrhage; Male; Naloxone; Rats; Rats, Brattleboro; Sodium Chloride; Vasopressins

Opiate receptor blockade with naloxone reverses the hypotension associated with severe hemorrhage in a variety of animal models. In the present study, we examined the mechanisms of naloxone's actions in conscious rabbits made hypotensive by hemorrhage. This was accomplished through pharmacological blockade of the efferent limbs of the sympathetic or parasympathetic nervous systems prior to naloxone injection. In addition, we examined the effects of naltrexone in the same model. Naloxone treatment in hypotensive-hypovolemic, conscious rabbits results in an increase in mean arterial blood pressure (BP) and a decrease in heart rate (HR). The bradycardia appears to be due to a reduction in beta-adrenergic and an increase in muscarinic-cholinergic activity. The pressor effect is apparently due to increased alpha-adrenergic receptor activation, and is accompanied by an increase in cardiac output, stroke volume, and total peripheral resistance. Naltrexone did not significantly affect BP but it did reduce HR. The results from the present study suggest that naloxone's effects are mediated by an integrated response of the sympathetic and parasympathetic nervous systems. The actions of naloxone may be mediated through antagonism of endogenous opiates.

Topics: Adrenergic Fibers; Animals; Atropine; Blood Pressure; Efferent Pathways; Heart Rate; Hemodynamics; Hemorrhage; Hypotension; Male; Naloxone; Naltrexone; Parasympathetic Nervous System; Phentolamine; Propranolol; Rats; Receptors, Adrenergic; Receptors, Cholinergic; Receptors, Opioid

Topics: Adult; Anesthesia; Anesthesia, General; Anesthesia, Inhalation; Endorphins; Female; Fentanyl; Genital Diseases, Female; Hemorrhage; Humans; Menstruation; Naloxone; Narcotics; Nociceptors; Pain, Postoperative; Pituitary Hormones, Anterior; Prospective Studies; Receptors, Opioid

The effects of naloxone on blood pressure and heart rate were studied in conscious, chronically prepared rabbits. In addition, the effects of barbiturate anesthesia on the response to naloxone were investigated. Initial surgery to implant arterial and venous catheters was performed under halothane anesthesia. Experiments were begun 10 days to 2 weeks later. The rabbits were divided into two groups: a normotensive group and a group made hypotensive by hemorrhage. In the normotensive rabbits, naloxone (2 mg/kg i.v.) did not alter mean arterial blood pressure (BP), pulse pressure, (PP), or heart rate (HR). However, a 5 mg/kg dose increased BP and PP, and decreased HR. In the hypotensive group, naloxone in a dose of 2, 3, or 5 mg/kg i.v. significantly increased BP and PP while decreasing HR in a dose-related manner. A dose of 0.2 mg/kg did not significantly alter any of the measured parameters. Pentobarbital anesthesia significantly reduced the effects of the 3 mg/kg naloxone dose in the hypotensive group. These actions of naloxone may be mediated through antagonism of endogenous opiates.

Topics: Animals; Blood Pressure; Dose-Response Relationship, Drug; Heart Rate; Hemorrhage; Hypotension; Male; Naloxone; Pentobarbital; Rabbits

Topics: Animals; Body Temperature; Bombesin; Cold Temperature; Hemorrhage; Humans; Injections, Intraventricular; Male; Naloxone; Oligopeptides; Peptides; Rats; Restraint, Physical; Stress, Psychological; Time Factors