beta-endorphin and Hypotension

Severe blood loss lowers arterial pressure through a central mechanism that is thought to include opioid neurons. In this study, we investigated whether hemorrhage activates proopiomelanocortin (POMC) neurons by measuring Fos immunoreactivity and POMC mRNA levels in the medial basal hypothalamus. Hemorrhage (2.2 ml/100 g body weight over 20 min) increased the number of Fos immunoreactive neurons throughout the rostral-caudal extent of the arcuate nucleus, the retrochiasmatic area and the peri-arcuate region lateral to the arcuate nucleus where POMC neurons are located. Double label immunohistochemistry revealed that hemorrhage increased Fos expression by beta-endorphin immunoreactive neurons significantly. The proportion of beta-endorphin immunoreactive neurons that expressed Fos immunoreactivity increased approximately four-fold, from 11.7+/-1.4% in sham-operated control animals to 42.0+/-5.2% in hemorrhaged animals. Hemorrhage also increased POMC mRNA levels in the medial basal hypothalamus significantly, consistent with the hypothesis that blood loss activates POMC neurons. To test whether activation of arcuate neurons contributes to the fall in arterial pressure evoked by hemorrhage, we inhibited neuronal activity in the caudal arcuate nucleus by microinjecting the local anesthetic lidocaine (2%; 0.1 or 0.3 microl) bilaterally 2 min before hemorrhage was initiated. Lidocaine injection inhibited hemorrhagic hypotension and bradycardia significantly although it did not influence arterial pressure or heart rate in non-hemorrhaged rats. These results demonstrate that hemorrhage activates POMC neurons and provide evidence that activation of neurons in the arcuate nucleus plays an important role in the hemodynamic response to hemorrhage.

Topics: Animals; Arcuate Nucleus of Hypothalamus; beta-Endorphin; Bradycardia; Hemorrhage; Hypotension; Hypothalamus; Hypothalamus, Middle; Immunohistochemistry; Injections; Lidocaine; Male; Neurons; Pro-Opiomelanocortin; Proto-Oncogene Proteins c-fos; Rats; Rats, Sprague-Dawley; RNA, Messenger

Heat stroke is characterized by hyperthermia, arterial hypotension, decreased baroreflex sensitivity, and increased serum levels of beta-endorphin. Whereas naltrexone may have therapeutic potential in heat stroke, the underlying mechanism remains unclear. We tested the hypothesis that naltrexone may attenuate heat stroke by reducing hyperthermia, hypotension, decreased baroreceptor sensitivity, and/or increased serum levels of beta-endorphin. Heat stroke was induced by exposing the anesthetized adult Sprague-Dawley rats in an incubator at 43 degrees C. The moment in which the mean arterial pressure dropped irreversibly from the peak level was taken as the onset of heat stroke. Control rats were exposed to 24 degrees C. Mean arterial pressure, baroreceptor sensitivity, and maximal reflex bradycardia, after the onset of heat stroke, were all significantly lower than in control rats. However, rectal temperature and serum levels of beta-endorphin were all greater after the onset of heat stroke. Intravenous delivery of naltrexone (10 mg/kg) 20 min before the initiation of heat stress, but not immediately at the onset of heat stroke, significantly attenuated the above-mentioned reactions. Accordingly, naltrexone improved survival during heat stroke. These results suggest that naltrexone protects against hypotension and decrement of both baroreceptor sensitivity and maximal reflex bradycardia during heat stroke by reducing both hyperthermia and increment of serum beta-endorphin and thus improves survival.

Topics: Animals; beta-Endorphin; Blood Pressure; Fever; Heart Rate; Heat Stroke; Hypotension; Male; Naltrexone; Narcotic Antagonists; Pressoreceptors; Rats; Rats, Sprague-Dawley

This study was conducted to more clearly delineate the possible role of endogenous opioid receptors and opioid peptides in general anesthesia-associated hypotension in rats. Exposure to 2% isoflurane in oxygen produced a triphasic change in mean arterial pressure (MAP), including an early phase in which MAP fell by -28.4 +/- 2.2%. The magnitude of this early-phase hypotension was attenuated in rats pretreated with intravenous (i.v.) mu-subtype-selective doses of either naloxone or methylnaloxone but not central doses of the selective mu-opioid antagonist beta-funaltrexamine. This early hypotensive phase was also reduced following i.v. pretreatment with antiserum against methionine-enkephalin but not beta-endorphin. These findings suggest that early-phase isoflurane-induced hypotension may be due to activation of peripheral mu-opioid receptors by an endogenous opioid peptide, possibly related to methionine-enkephalin.

Topics: Anesthetics, Inhalation; Anesthetics, Intravenous; Animals; Antibodies, Blocking; beta-Endorphin; Blood Pressure; Endorphins; Enkephalin, Methionine; Hot Temperature; Hypotension; Injections, Intraventricular; Isoflurane; Male; Naloxone; Naltrexone; Narcotic Antagonists; Pain Measurement; Rats; Rats, Sprague-Dawley; Reaction Time; Receptors, Opioid; Urethane

The early stress responses to hemorrhagic shock, trauma and endotoxicosis are associated with an early proinflammatory response characterized by increased gene expression of proinflammatory cytokines, PMN influx and accumulation in the lung and apoptosis. The central role of the neuroendocrine system in modulating these proinflammatory responses has been strongly suggested by recent studies.. To examine the role of noradrenergic innervation in modulating the early increase in lung and spleen content of TNF-alpha in response to fixed-pressure (40 mm Hg) hemorrhage in vivo.. Conscious unrestrained nonheparinized male Sprague-Dawley rats (n = 42) were randomized to receive intraperitoneally either 6-hydroxy-dopamine (6-OHDA; chemical sympathectomy, SNSx) or saline (0.3 ml) prior to undergoing hemorrhage followed by fluid resuscitation with lactated Ringer's solution. Animals were sacrificed at completion of the resuscitation period and tissue samples (lung and spleen) excised for determination of TNF-alpha content, myeloperoxidase activity and apoptosis.. Hemorrhage resulted in an immediate marked elevation in circulating epinephrine and norepinephrine levels (10- and 2-fold, respectively), increasing their plasma ratio to 6:1. SNSx depleted tissue stores of norepinephrine (80%), did not alter basal plasma levels of epi- or norepinephrine or the hemorrhage-induced rise in epinephrine, but completely prevented the rise in circulating norepinephrine. Hemorrhage increased lung and spleen contents of TNF-alpha (55 and 72%, respectively). SNSx significantly enhanced the hemorrhage-induced rise in lung TNF in response to hemorrhage.. These results show a suppressive role for noradrenergic innervation on the hemorrhage-induced increase in tissue TNF-alpha content in vivo. We speculate that the effects of norepinephrine are protective from tissue injury but are likely to contribute to the generalized immunosuppression following trauma.

Topics: Animals; Apoptosis; beta-Endorphin; Catecholamines; Corticosterone; Hypotension; Lung; Male; Neuroimmunomodulation; Neurosecretory Systems; Neutrophil Activation; Norepinephrine; Oxidopamine; Peroxidase; Rats; Rats, Sprague-Dawley; Shock, Hemorrhagic; Spleen; Sympathectomy, Chemical; Sympathetic Fibers, Postganglionic; Tumor Necrosis Factor-alpha; Up-Regulation; Wounds and Injuries

beta-endorphin and cortisol were measured in cerebrospinal fluid (CSF) and plasma by radioimmunological method (RIA) in two groups of rabbits with spinal cord traumatic injuries at cervical and lumbar levels, respectively with and without concomitant spinal shock and arterial hypotension, and in a group of sham operated animals as controls. The two groups with spinal lesions displayed a significant beta-endorphin increase in CSF, whereas the cortisol level remained unchanged both in the spinal traumatized rabbits and in controls. Both the opioid and the cortisol concentration rose significantly in plasma in all three groups and in particular resulted significantly higher in the cervical traumatized group where spinal trauma was associated with spinal shock and hypotension. However, no significant difference was found when beta-endorphin concentrations in plasma were compared between the sham operated animals and the spinal lumbar traumatized animals without concomitant spinal shock. The results seem to suggest that the beta-endorphin increase in CSF is related to the nervous tissue lesion, while its increase in plasma, like that of cortisol, is due to surgery or other stress factors inherent in the experiment. This independent behaviour of beta-endorphin in plasma and in CSF suggests its different origin in these two compartments.

Topics: Animals; Arousal; beta-Endorphin; Female; Hydrocortisone; Hypotension; Male; Rabbits; Radioimmunoassay; Shock; Spinal Cord; Spinal Cord Injuries

We studied the course of plasma levels of the stress markers adrenocorticotropic hormone (ACTH), cortisol, human growth hormone (h-GH), beta-endorphin, and prolactin during retrieval surgery in eleven brain-dead organ donors scheduled for multiple organ explantation. Donors were divided into two groups according to hemodynamic stability. Hormones demonstrated a great variability in plasma levels and in the pattern of reaction, revealing a different degree of remaining pituitary function. Beta-Endorphin was the only stress hormone that showed a response to surgical stimuli in six patients. Only three of them developed a concomitant rise in ACTH. Cortisol, prolactin, and h-GH plasma levels did not change during the observation period. In the three cases with a slight elevation in ACTH, no subsequent change in cortisol was detectable. Beta-Endorphin showed greater variability and a tendency to higher levels in the group presenting with a higher arterial pressure, which resulted in a significant difference (P < 0.005) when distributions were compared using the Mann-Whitney U-test. No correlation was found between hypotensive episodes and deficiencies of other stress hormones. We conclude that pituitary function varies considerably in brain-dead organ donors without demonstrating a correlation to the onset of hypotension. Thus, we feel no need for a substitution treatment with any of the hormones investigated prior to organ explanation.

Topics: Adrenocorticotropic Hormone; Adult; beta-Endorphin; Brain Death; Endocrine Glands; Female; Growth Hormone; Humans; Hydrocortisone; Hypotension; Male; Middle Aged; Prolactin; Stress, Physiological; Tissue and Organ Procurement

Treatment of rats for 4 days with alpha-methyldopa, 200 mg/kg/day i.p., increases steady state levels of proopiomelanocortin (POMC) mRNA in the mediobasal hypothalamus, as measured by DNA excess solution hybridization. The increase is prevented by parallel treatment with yohimbine, 2 mg/kg/day i.p., but not by naltrexone, 2 mg/kg/day i.p. Treatment with the peripheral vasodilator hydralazine, 2 mg/kg/day, does not affect POMC mRNA levels. In situ hybridization histochemistry with a cRNA probe for POMC indicates that POMC-containing cells are located within the confines of the arcuate nucleus both in control and in alpha-methyldopa-treated rats, and confirms the increase in POMC mRNA in the latter. Microinjection of 2 micrograms of alpha-methylnorepinephrine unilaterally into the arcuate nucleus of urethane-anesthetized rats causes hypotension and bradycardia, which can be inhibited by 200 ng of yohimbine microinjected into the same site, or by 100 ng l-naloxone microinjected into the ipsilateral nucleus tractus solitarii, but not into the arcuate nucleus. These findings are interpreted to indicate that activation of alpha 2-adrenergic receptors located on POMC-containing neurons in the arcuate nucleus causes beta-endorphin release and stimulation of opiate receptors in the NTS, which results in hypotension and bradycardia, and that this mechanism contributes to the hypotensive action of alpha-methyldopa.

Topics: Adrenergic alpha-Agonists; Animals; Arcuate Nucleus of Hypothalamus; beta-Endorphin; Bradycardia; Hypotension; In Situ Hybridization; Male; Methyldopa; Microinjections; Neurons; Nordefrin; Pro-Opiomelanocortin; Rats; Rats, Sprague-Dawley; Receptors, Adrenergic, alpha; RNA, Messenger; Yohimbine

Topics: Angiotensin-Converting Enzyme Inhibitors; beta-Endorphin; Humans; Hypotension; Syncope

Endogenous opioids have a tonic inhibitory effect on sympathetic tone and have been implicated in the pathophysiology of vasodepressor syncope. Plasma beta endorphin concentrations increase after vasodepressor syncope induced by exercise or by fasting.. To take frequent samples for plasma beta endorphin estimation during tilt testing, and to determine whether plasma beta endorphin increased before the start of syncope.. 24 patients undergoing tilt testing for investigation of unexplained syncope.. Tertiary referral centre.. Blood samples were obtained during 70 degrees head up tilt testing. Plasma beta endorphin concentrations were estimated by radioimmunoassay (mean(SD) pmol/l).. Patients with a positive test showed a rise in beta endorphin concentrations before syncope (baseline 4.4(1.5) v start of syncope 8.5(3.1), p < 0.002). In contrast, patients with a negative test showed no change in beta endorphin concentrations (baseline 3.4(1.0) v end of test 4.5(2.3), NS). After syncope all patients showed a large secondary increase in beta endorphins (32.3(18.6)).. An increase in plasma beta endorphins precedes vasodepressor syncope. This finding supports a pathophysiological role for endogenous opioids.

Topics: Adolescent; Adult; Aged; beta-Endorphin; Female; Humans; Hypotension; Male; Middle Aged; Posture; Radioimmunoassay; Reproducibility of Results; Syncope; Vascular Resistance

During bicarbonate hemodialysis, there is an increase in peripheral vascular resistance of nonadrenergic origin, counteracting the hypotensive effect of fluid removal during the course of the dialysis. In this study, the plasma levels of vasoactive regulatory peptides, noradrenaline and renin, were investigated in 11 patients with chronic renal failure during standard bicarbonate hemodialysis (STHD) for 270 min. As regards vasoconstrictors, an increase in gamma 2-melanocyte-stimulating hormone (gamma 2-MSH), neuropeptide Y (NPY) and plasma renin activity (PRA) occurred. However, arginine vasopressin and noradrenaline were unchanged. With respect to vasodilators, calcitonin gene-related peptide was not changed. An initial increase in beta-endorphin (beta-END) occurred, followed by a decrease during the remaining part of the treatment. Motilin decreased during the first part of the treatment but increased to the baseline level during the latter part. An increase in substance P was observed while vasoactive intestinal peptide decreased. We conclude that an increase in vasoconstricting substances (gamma 2-MSH, NPY, PRA) occurs during STHD, probably owing to the decrease in plasma volume. With the exception of beta-END, the changes in vasodilators were fairly small. The data suggest that vasoactive substances might participate in the hemodynamic response to hemodialysis.

Topics: Adult; Aged; Aged, 80 and over; Arginine Vasopressin; beta-Endorphin; Bicarbonates; Calcitonin Gene-Related Peptide; Female; Hemodynamics; Humans; Hypotension; Kidney Failure, Chronic; Male; Melanocyte-Stimulating Hormones; Middle Aged; Neuropeptide Y; Neuropeptides; Norepinephrine; Renal Dialysis; Renin

This study was designed to determine if opioids were detectable in cerebrospinal fluid (CSF) and if these concentrations were altered by hemorrhagic hypotension. This study was further designed to determine the effects of topically administered opioids on pial arteriolar diameter during normotension and hypotension. Closed cranial windows were used to determine pial arteriolar diameter. Periarachnoid cortical and cisterna magna CSF was collected from piglets during normotension and hypotension (systemic arterial pressure decreased from 63 +/- 1 to 33 +/- 1 mm Hg). Opioid profiles were assessed qualitatively by radioreceptor assay, and individual opioids were measured quantitatively by radioimmunoassay. Periarachnoid cortical and cisterna magna CSF methionine enkephalin-, leucine enkephalin-, dynorphin-, and beta-endorphin-like receptor active values all were increased by hypotension. When quantified by radioimmunoassay, periarachnoid cortical CSF values for methionine enkephalin-like immunoreactivity were 1,167 +/- 58 and 2,975 +/- 139 pg/ml for normotension and hypotension, respectively. Periarachnoid cortical CSF radioimmunoassay values for dynorphin-like immunoreactivity were 15 +/- 2 and 28 +/- 2 pg/ml for normotension and hypotension, respectively. When applied topically to the cortical surface, synthetic methionine enkephalin increased pial arteriolar diameter (134 +/- 4, 158 +/- 4, and 163 +/- 4 microns for control, 574 pg/ml [10(-10) M], and 5,740 pg/ml [10(-9) M], respectively). Similarly, topical synthetic leucine enkephalin and dynorphin elicited pial arteriolar dilation. However, beta-endorphin produced arteriolar constriction. Hypotension attenuated methionine and leucine enkephalin-induced dilation and reversed dynorphin-induced dilation to concentration-dependent constriction. beta-Endorphin-induced constriction was not changed by hypotension. Therefore, opioids could contribute to the control of the cerebral circulation during hypotension.

Topics: Animals; Animals, Newborn; beta-Endorphin; Cerebral Arteries; Dynorphins; Endorphins; Enkephalin, Leucine; Enkephalin, Methionine; Hemorrhage; Hypotension; Muscle, Smooth, Vascular; Radioimmunoassay; Radioligand Assay; Reference Values; Swine; Vasodilation

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

The possible role of the endogenous opioid system in the central hypotensive mechanism of action of alpha-methyldopa was investigated. Conscious normotensive Wistar rats were used in this study and all treatments were given intracisternally. Pretreatment with the opiate receptor antagonist naltrexone resulted in a parallel shift to the right of the dose-response curve for alpha-methyldopa, both for blood pressure and heart rate. In addition, when increasing doses of naltrexone and a constant dose of alpha-methyldopa were used the opiate receptor antagonist inhibited dose-dependently alpha-methyldopa-induced hypotension but not the bradycardia. Administration of naltrexone after the injection of alpha-methyldopa failed to reverse or inhibit alpha-methyldopa-induced hypotension, indicating that the interaction between alpha-methyldopa and the endogenous opioid system occurs at the start of the action of alpha-methyldopa. An antiserum against endorphins also inhibited the fall in blood pressure after alpha-methyldopa. These findings indicate that stimulation of opiate receptors, probably by an endorphin, is involved in the mechanism of action of alpha-methyldopa and that this stimulation seems to occur at the start of the action of alpha-methyldopa.

Topics: Animals; beta-Endorphin; Bradycardia; Dose-Response Relationship, Drug; Heart Rate; Hypotension; Immune Sera; Male; Methyldopa; Naloxone; Naltrexone; Rats; Rats, Inbred Strains

Twenty-nine premature infants were studied to determine whether neonatal asphyxia, apnea, and low blood pressure in the first day of life are associated with elevated plasma beta-endorphin concentrations. Plasma beta-endorphin levels were determined at 0.5 to 2, 4 to 6, and 18 to 24 hours of life, using radioimmunoassay. Premature infants with moderate or severe asphyxia (n = 19) had higher levels at 0.5 to 2 hours of age (32.1 +/- 6.7 vs 16.4 +/- 7.4 pmol/L) and significantly higher levels at 4 to 6 hours of age (50.4 +/- 10.0 vs 22.9 +/- 9.2 pmol/L) compared with the ten nonasphyxiated premature infants. A significant elevation in levels at age 0.5 to 2 hours (39.4 +/- 9.9 vs 17.7 +/- 4.4 pmol/L) and age 4 to 6 hours (59.3 +/- 13.8 vs 27.1 +/- 17.1 pmol/L) was observed in premature infants with low blood pressure or impaired perfusion (n = 12) who required the administration of volume expanders. No differences were observed in premature infants with and without apnea. It may be speculated that the increased endogenous release of beta-endorphins in response to perinatal asphyxia may play a role in the pathogenesis of shock observed in the first day of life.

Topics: Apnea; Asphyxia Neonatorum; beta-Endorphin; Endorphins; Humans; Hypotension; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature, Diseases; Radioimmunoassay

The role which beta-endorphin plays in the pathogenesis of hemorrhagic hypotension is controversial. In the present experiment, 20 ml/kg of blood was bled from ten healthy male baboons (Papio anubis) over 60 min and then retransfused over the next 30 min. We found that the mean plasma beta-endorphin level increased 109% above baseline (p less than .05) within 15 min after starting hemorrhage, and rapidly returned to a baseline concentration with retransfusion. We conclude that in a primate species, circulating endogenous opioid peptide concentrations increase rapidly in response to sublethal hemorrhagic hypotension and normalize with restoration of the baseline intravascular volume. These findings support the concept that endogenous opioid peptides may mediate the hypotension of shock states.

Topics: Animals; beta-Endorphin; Blood Transfusion, Autologous; Blood Volume; Endorphins; Hemorrhage; Hypotension; Male; Papio

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

In an attempt to determine whether plasma beta-endorphin (beta-ED) concentrations correlate with occurrence of apnea in preterm infants, measurements were made in three groups of infants. The control group consisted of 11 infants with a mean (+/- SEM) gestational age of 30.5 +/- 0.8 weeks, a mean (+/- SEM) birthweight of 1650 +/- 180 g, and a mean (+/- SEM) postnatal age of 1.3 +/- 0.5 days. Eight infants with apnea, bradycardia, and associated hypotension had a mean (+/- SEM) gestational age, birthweight and postnatal age of 30 +/- 0.9 weeks, 1165 +/- 90 g, and 7.8 +/- 1.9 days, respectively. The third group consisted of eight infants experiencing apnea alone without bradycardia and had a mean (+/- SEM) gestational age, birthweight, and postnatal age of 31 +/- 0.8 weeks, 1380 +/- 125 g, and 2.6 +/- 0.9 days, respectively. The last two groups of infants suffered varying degrees of apnea, but differed in their severity. The plasma endorphin concentrations (+/- SEM) were 26.9 +/- 2, 68.0 +/- 9.0, and 39.6 +/- 2.0 pg/ml, respectively, for the previously described three groups. Significant elevation in beta-ED concentration was observed in the severely apneic infants with bradycardia when compared to the other two groups. The association of increased plasma beta-ED release with severe apneic spells may suggest that these endogenous opiates play a role in the pathophysiology of apnea of prematurity.

Topics: Apnea; beta-Endorphin; Bradycardia; Endorphins; Humans; Hypotension; Infant, Newborn; Infant, Premature, Diseases; Radioimmunoassay; Recurrence

Previous studies established that naloxone reverses hypotension in endotoxin, hemorrhagic, and spinal shock. We studied endotoxin shock in hypophysectomized (Hx) rats, which have little circulating beta-endorphin. Hx or intact rats received surgically implanted jugular catheters for drug injection and aortic catheters for arterial blood pressure (MAP) recording. On the second day after implantation, rats were pretreated with either naloxone or saline. Two minutes later each rat received endotoxin. Following endotoxin, all rats showed a brief biphasic hypertensive-hypotensive response followed by stabilization of MAP near baseline. Within 20 min, all Hx rats, regardless of pretreatment, and the saline-treated intact rats, showed progressive hypotension (P less than 0.005). Only the naloxone-pretreated intact rats maintained a stable MAP. Plasma endorphin measured at 20 min was undetectable in Hx rats in contrast to intact rats (P less than 0.001); plasma corticosterone levels were likewise suppressed in the Hx rats (P less than 0.01). Thus (1) naloxone protected only the rats with an intact pituitary-adrenal-sympathetic system, and (2) pituitary endorphin is not required to generate endotoxin shock in hypophysectomized rats.

Topics: Animals; beta-Endorphin; Blood Pressure; Corticosterone; Endorphins; Hypophysectomy; Hypotension; Male; Naloxone; Pituitary Gland; Rats; Rats, Inbred Strains; Shock, Septic

Topics: Adrenal Glands; Animals; beta-Endorphin; Endorphins; Hypotension; Male; Rats