beta-endorphin and Hypertension

It is generally accepted that the essential hypertension (EH) is caused by interactions among congenital gene, multiple pathogenetic pressor factors, and disorder of physiologic depressor factors. The central nervous system may play a key role in the development of EH. The underlying mechanisms, however, are not well understood. Studies show that peptidergic transmitters in the limbic forebrain are involved in long-term regulation of arterial pressure and in the pathogenesis of EH. In the limbic forebrain there are peptidergic pressor and depressor circuits. The former includes corticotropin releasing factor-, substance P-, and angiotensin II-circuits; and the latter includes beta-endorphin- and atrial natriuretic peptide-circuits. These circuits extensively interconnect and interact with each other. The altered functions of them may be the pathogenesis of EH. In this review, we focus on the roles of limbic peptidergic circuits in regulation of arterial pressure, relevant to the neurogenetic mechanisms in developing EH.

Topics: Angiotensin II; Animals; Atrial Natriuretic Factor; beta-Endorphin; Blood Pressure; Corticotropin-Releasing Hormone; Humans; Hypertension; Limbic System; Neuropeptides; Substance P

Topics: Adrenocorticotropic Hormone; Adult; beta-Endorphin; Blood Pressure; Body Weight; Circadian Rhythm; Female; Humans; Hydrocortisone; Hypertension; Male; Obesity

Essential hypertension is characterised by reduced pain sensitivity. Hypertensive hypoalgesia has been attributed to elevated endogenous opioids and/or increased activation of descending pain modulation systems. A double-blind placebo-controlled design compared the effects of naltrexone and placebo on cold and ischemic pain in unmedicated newly-diagnosed patients with essential hypertension. Patients performed a cold pressor task while resting and while performing a distracting secondary task. They also performed a forearm ischemia task while resting. Although the cold pressor and ischemia tasks elicited significant increases in pain and blood pressure, pain ratings and pressor responses did not differ between naltrexone and placebo. Cold pain was reduced by distraction compared to rest. The finding that opioid blockade with naltrexone did not moderate the pain and pressor responses to cold and ischemia suggests that pain and associated blood pressure responses are not modulated by opioids in hypertension. The finding that the distracting secondary task successfully reduced pain ratings suggests normal supraspinal pain modulation in essential hypertension.

Topics: Adult; Attention; beta-Endorphin; Cold Temperature; Double-Blind Method; Female; Heart Rate; Humans; Hypertension; Male; Myocardial Ischemia; Naltrexone; Narcotic Antagonists; Pain; Pain Measurement; Touch

The opioid system is involved in blood pressure regulation in both normal humans and patients with essential hypertension.. The objective of the study was to investigate the effects of a high-dose infusion of beta-endorphin, an opioid peptide, on blood pressure and on the hormonal profile in healthy subjects and in hypertensive patients and the mediation played by opioid receptor agonism.. According to a randomized double-blind design, 11 healthy subjects (controls) and 12 hypertensive inpatients (mean age, 38.9 and 40.4 yr, respectively) received 1-h iv infusion of beta-endorphin (250 mug/h) and, on another occasion, the same infusion protocol preceded by the opioid antagonist naloxone (8 mg).. Hemodynamic and hormonal measurements were performed at established times during the infusion protocols.. At baseline, circulating beta-endorphin, norepinephrine, and endothelin-1 in hypertensive patients were significantly (P < 0.05) higher than in controls. In controls, beta-endorphin reduced blood pressure (P < 0.01) and circulating norepinephrine (P < 0.02) and increased plasma atrial natriuretic factor (P < 0.003) and GH (P < 0.0001). In hypertensive patients, beta-endorphin decreased systemic vascular resistance (P < 0.0001), blood pressure (P < 0.0001), and plasma norepinephrine (P < 0.0001) and endothelin-1 (P < 0.0001) and raised circulating atrial natriuretic factor (P < 0.0001), GH (P < 0.0001), and IGF-I (P < 0.0001). These hemodynamic and hormonal responses to beta-endorphin in hypertensive patients were significantly (P < 0.0001) greater than in controls but were annulled in all individuals when naloxone preceded beta-endorphin infusion.. High doses of beta-endorphin induce hypotensive and beneficial hormonal effects in humans, which are enhanced in essential hypertension and are mediated by opioid receptors.

Topics: Adult; beta-Endorphin; Blood Pressure; Dose-Response Relationship, Drug; Double-Blind Method; Female; Hemodynamics; Hormones; Humans; Hypertension; Male; Middle Aged; Naloxone; Narcotic Antagonists; Receptors, Opioid

After hyperventilation, systolic and diastolic blood pressure (BP) significantly decreased in 14 hypertensive patients (group 1), did not change in 9 (group 2) and increased in 8 (group 3). Basal BP, norepinephrine and dynorphin B levels were higher in group 1 than in groups 2 and 3. The decrease in BP after hyperventilation was associated with a decrease in plasma norepinephrine, Met-enkephalin and dynorphin B and an increase in beta-endorphin. Naloxone abolished the hyperventilation-induced BP and norepinephrine decreases. Our findings indicate that hyperventilation may select hypertensive patients with different sympatho-adrenergic activity and that the increase in beta-endorphin reduces BP response to hyperventilation in patients with high sympatho-adrenergic tone.

Topics: Aged; beta-Endorphin; Blood Pressure; Cross-Over Studies; Dynorphins; Enkephalin, Methionine; Female; Heart Rate; Humans; Hypertension; Hyperventilation; Male; Middle Aged; Naloxone; Norepinephrine; Time Factors

The present study was designed to investigate the integrated effects of the beta-1-selective blocker with vasodilator properties, nebivolol, on systemic haemodynamics, neurohormones and energy metabolism as well as oxygen uptake and exercise performance in physically active patients with moderate essential hypertension (EH).. Eighteen physically active patients with moderate EH were included: age: 46.9 +/- 2.38 years, weight: 83.9 +/- 2.81 kg, blood pressure (BP): 155.8 +/- 3.90/102.5 +/- 1.86 mm Hg, heart rate: 73.6 +/- 2.98 min(-1). After a 14-day wash-out period a bicycle spiroergometry until exhaustion (WHO) was performed followed by a 45-min submaximal exercise test on the 2.5 mmol/l lactate-level 48 h later. Before, during and directly after exercise testing blood samples were taken. An identical protocol was repeated after a 6-week treatment period with 5 mg nebivolol/day.. Nebivolol treatment resulted in a significant (P < 0.01) decrease in systolic and diastolic BP and heart rate at rest and during maximal and submaximal exercise. Maximal physical work performance, blood lactate and rel. oxygen uptake (rel. VO(2)) before and after nebivolol treatment at rest and during maximal and submaximal exercise remained unaltered. Free fatty acid, free glycerol, plasma catecholamines, beta-endorphines and atrial natriuretic peptide (ANP) increased before and after treatment during maximal and submaximal exercise but remained unaltered by nebivolol treatment. In contrast, plasma ANP levels at rest were significantly higher in the presence of nebivolol, endothelin-1 levels were unchanged.. Nebivolol was effective in the control of BP at rest and during exercise in patients with EH. Furthermore, nebivolol did not negatively affect lipid and carbohydrate metabolism and substrate flow. The explanation for the effects on ANP at rest remain elusive. This pharmacodynamic profile of nebivolol is potentially suitable in physically active patients with EH.

Topics: Adrenergic beta-Antagonists; Adult; Analysis of Variance; Benzopyrans; beta-Endorphin; Blood Glucose; Catecholamines; Chromatography, High Pressure Liquid; Energy Metabolism; Ethanolamines; Exercise Test; Hemodynamics; Human Growth Hormone; Humans; Hydrocortisone; Hypertension; Immunoenzyme Techniques; Insulin; Lactic Acid; Lipids; Middle Aged; Nebivolol; Neurosecretory Systems; Physical Exertion; Physical Fitness; Pilot Projects; Radioimmunoassay; Vasodilator Agents

Dynamic exercise acutely and transiently lowers resting blood pressure in hypertensive men and is termed postexercise hypotension (PEH). We examined 18 premenopausal women (7 hypertensive and 11 normotensive) to determine if PEH occurs in women and to elucidate possible hemodynamic and hormonal mechanisms.. Patients wore an ambulatory blood pressure monitor throughout the day after 40 minutes of a rest sham session and 40 minutes of cycle exercise, of which 30 minutes was performed at 60% of maximal oxygen consumption. Cardiac output and total systemic vascular resistance were determined by Doppler echocardiography before and 15 minutes after sham and exercise. Catecholamines, plasma renin activity, and beta-endorphin were measured over this same period. PEH occurred only in the hypertensive women. Systolic, diastolic, and mean arterial blood pressure decreased in the hypertensive women by a mean of 9.5 +/- 2. 8 mm Hg (P <.01), 6.7 +/- 2.4 mm Hg (P <.05), and 7.7 +/- 2.4 mm Hg (P <.05), respectively, for up to 7 hours after versus before exercise, whereas blood pressure was similar in the normotensive women (P >.05). After exercise, total systemic vascular resistance was lower (P <.01), and cardiac output, catecholamines, and plasma renin activity were greater (P <.01) than before exercise in both groups of women.. PEH was observed for up to 7 hours after exercise in mildly hypertensive women and was not explained by the hemodynamic and hormonal adjustments that occurred after exercise. The magnitude and duration of PEH may be sufficient to normalize the blood pressure of certain hypertensive women throughout most of the day.

Topics: Adult; beta-Endorphin; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Cardiac Output; Catecholamines; Echocardiography, Doppler; Electrocardiography; Exercise; Exercise Test; Female; Humans; Hypertension; Premenopause; Renin; Rest; Risk Factors; Vascular Resistance

To investigate the effects of the endogenous opioid system on plasma atrial natriuretic factor (ANF) levels during sympathetic hyperactivity.. We studied the young normotensive offspring of parents who both had essential hypertension, who are characterized by a hyperactive sympathetic nervous system.. We assessed plasma beta-endorphin, met-enkephalin, dynorphin B, ANF and noradrenaline levels, blood pressure and heart rate values in eight normotensive offspring and in 10 young normotensive subjects with no family history of hypertension (controls) at rest and during two exercise tests: the first test performed with the infusion of placebo (1.5 ml/min saline) and the second test with the infusion of an opioid antagonist (9.5 micrograms/kg per min naloxone hydrochloride). ANF and opioids were radioimmunoassayed after chromatographic pre-extraction.. At rest plasma met-enkephalin, dynorphin B, ANF and noradrenaline values in the normotensive offspring were significantly higher than in the controls. Exercise with placebo significantly raised all hormonal and haemodynamic parameters in the two groups. This increase was significantly higher in the normotensive offspring than in the controls. Naloxone did not modify any parameter in either group at rest, but it enhanced further the rise in plasma noradrenaline levels induced by exercise in both groups. A similar effect of naloxone during exercise was observed for plasma ANF levels in the normotensive offspring.. Our findings show that plasma met-enkephalin, dynorphin B, ANF and noradrenaline levels at rest and during exercise are higher in normotensive offspring than in controls. The effects of naloxone indicate that in normotensive offspring at rest the opioid system does not affect ANF release, whereas during exercise it attenuates ANF hypersecretion, possibly by reducing noradrenaline release.

Topics: Adult; Atrial Natriuretic Factor; beta-Endorphin; Disease Susceptibility; Dynorphins; Endorphins; Enkephalin, Methionine; Exercise Test; Female; Hemodynamics; Humans; Hypertension; Male; Naloxone; Norepinephrine; Opioid Peptides; Physical Exertion; Radioimmunoassay

The purpose of the present study was to determine if opioid agonism (beta-endorphin) and antagonism (Naloxone) exert rheological and cardiovascular effects in normal humans and in patients with essential hypertension. Eight hypertensive patients were matched for age, sex, and body habitus (body mass index, waist to hip ratio) with eight normotensive healthy subjects. In all subjects, heart rate and blood pressure (continuous automatic recording), blood and plasma viscosity, fibrinogen, hematocrit, and platelet aggregation to ADP were evaluated during an infusion of human synthetic beta-endorphin (0.5 mg/h). On a different day and in randomized order, the subjects were submitted to another beta-endorphin infusion preceded by an i.v. naloxone bolus (5 mg in 5 min). beta-Endorphin and naloxone failed to significantly alter heart rate or blood pressure in both normotensive and hypertensive subjects. In hypertensive patients, beta-endorphin significantly increased blood viscosity and ADP-induced platelet aggregation, but only the former effect was naloxone-sensitive. In normotensive subjects, beta-endorphin caused a transient but significant decrease of platelet aggregation that was reversed by naloxone. These data suggest that beta-endorphin may play some role in the inhibitory control of platelet aggregation in normal subjects. An altered responsiveness of some rheological determinants to beta-endorphin seems to be present in human hypertension.

Topics: Adenosine Diphosphate; Adult; beta-Endorphin; Blood Pressure; Blood Viscosity; Cardiovascular System; Female; Fibrinogen; Heart Rate; Hematocrit; Humans; Hypertension; Male; Middle Aged; Naloxone; Platelet Aggregation; Rheology

The central alpha-2-adrenergic receptor agonist, clonidine (300 micrograms daily) significantly increased the plasma beta-endorphin-like immunoreactivity (beta ELI) in 12 patients with mild to moderate essential hypertension in a randomized, crossover study. A significant linear correlation between the increase in plasma beta ELI and the decrease in blood pressure (both systolic and diastolic) was found after clonidine administration. The role of the reduced central sympathetic tone, induced by alpha-2-adrenoceptor stimulation, in the elevation of circulating beta ELI can be suggested. The plasma beta ELI increased also significantly after the dopaminergic D-2 receptor agonist, bromocryptine treatment, (5 mg, daily) in 13 patients with borderline and mild essential hypertension in a randomized, crossover study. A significant drop in circulating noradrenaline and in arterial blood pressure and a significant linear correlation between the changes of plasma noradrenaline level and blood pressure was found after bromocryptine administration. There was no correlation between the rise in plasma beta ELI and the decrease in blood pressure after bromocryptine. The importance of the central sympathetic activity and not only a direct pituitary dopaminergic agonist effect on the beta-endorphin secretion can be stressed in the effect of bromocryptine on the immunoreactive beta-endorphin level.

Topics: Adult; beta-Endorphin; Blood Pressure; Bromocriptine; Clonidine; Dopamine; Heart Rate; Humans; Hypertension; Middle Aged; Norepinephrine; Prolactin; Sympathetic Nervous System

The effects of fish oil and naloxone on blood pressure, catecholamines, and endorphins during the cold pressor test were evaluated in a randomized, double-blind, placebo-controlled, two-way crossover trial of normotensive and medication-free hypertensive men (n = 13 each). Subjects were given 5 gm omega-3 fatty acids per day or placebo for 30 days with a 1-month washout between interventions. The cold pressor test (hand in ice water for 5 minutes) was done at the end of the treatment periods. Intravenous naloxone (10 mg) or placebo was given before the cold pressor test. Fish oil-treated, normotensive, or hypertensive groups had similar changes in blood pressure, plasma catecholamine levels, and beta-endorphins during the cold pressor test, but naloxone treatment was associated with fivefold and tenfold increases in plasma epinephrine and cortisol levels, respectively. Naloxone may modulate sympathomedullary discharge through blockade of endorphin activity. It is unlikely that endorphins are involved in the blood pressure increase during the cold pressor test or that fish oil alters this response.

Topics: Adult; beta-Endorphin; Blood Pressure; Chromatography, High Pressure Liquid; Cold Temperature; Double-Blind Method; Epinephrine; Fatty Acids, Omega-3; Fish Oils; Humans; Hydrocortisone; Hypertension; Infusions, Intravenous; Naloxone; Norepinephrine; Pain Measurement; Random Allocation

An evaluation of the effect of mental relaxation treatment on endogenous opioid activity and vascular reactivity in 20 patients with labile essential hypertension has demonstrated that mental relaxation treatment results in a significantly greater drop in arterial BP, as compared to pharmacologic placebo, and is associated with the improvement of the patients' psychological status, lesser psychophysiologic and vascular reactivity, and a smaller beta-endorphin increment under emotional stress.

Topics: Adult; beta-Endorphin; Biofeedback, Psychology; Blood Pressure; Humans; Hypertension; Male; Middle Aged; Relaxation Therapy

The role of alpha 2-adrenoceptor stimulation by clonidine on the secretion of beta-endorphin, ACTH, and cortisol in essential hypertension and obesity was studied in 45 subjects: 15 non-obese hypertensives, 10 obese hypertensives, 11 obese normotensives, and 9 healthy subjects. The circadian rhythm of plasma beta-endorphin, ACTH, and cortisol was determined after placebo and after three days on clonidine 0.45 mg daily. Clonidine lowered the blood pressure and blood ACTH and cortisol levels in all the subjects. A significant decrease in beta-endorphin after clonidine occurred in the healthy subjects. In obese normotensives basal beta-endorphin concentrations were significantly higher than in healthy subjects and did not change after clonidine. In about 50% of non-obese and obese hypertensives a significant increase in beta-endorphin secretion after clonidine was noted (responders). In the subgroup of non-obese hypertensive responders no circadian rhythm of beta-endorphin was observed. The results suggest that adrenergic regulation of beta-endorphin secretion is altered in obesity and in certain patients with essential hypertension.

Topics: Adrenocorticotropic Hormone; Adult; beta-Endorphin; Circadian Rhythm; Clonidine; Female; Humans; Hydrocortisone; Hypertension; Male; Obesity; Time Factors

In a randomized, double-blind crossover study 13 untreated patients with mild essential hypertension were exposed to submaximal bicycle exercise. Sixty minutes before ergometry 10 mg metoclopramide or placebo, and 10 min before exercise 0.4 mg naloxone or placebo, were given intravenously. Plasma adrenocorticotrophic hormone, beta-endorphin and cortisol levels increased significantly after ergometry, whether performed after placebo, naloxone, metoclopramide or metoclopramide + naloxone treatment. However, only naloxone administration potentiated plasma adrenocorticotrophic hormone, beta-endorphin and cortisol responses to workload. Plasma levels of adrenocorticotrophic hormone, beta-endorphin and cortisol were 45 +/- 14 pg/ml, 6.2 +/- 1.2 pmol/l and 141 +/- ng/ml, respectively, after ergometry, when performed after placebo, but these values were increased to 61 +/- 10 pg/ml, 11.4 +/- 2.8 pmol/l and 207 +/- 22 ng/ml, respectively, after naloxone treatment. This naloxone-induced potentiation of hormonal release was blocked by metoclopramide pretreatment, suggesting a close interaction between dopaminergic and opioidergic mechanisms, regulating hormonal responses to physical exercise.

Topics: beta-Endorphin; Dopamine; Female; Humans; Hypertension; Male; Metoclopramide; Naloxone; Physical Exertion; Stress, Physiological

Successful prevention and treatment of hypertension depend on the appropriate combination of antihypertensive drug therapy and nondrug lifestyle modification. While most hypertension guidelines recommend moderate- to high-intensity exercise, we decided to explore a mild yet effective type of exercise to add to hypertension management, especially in populations with complications or frailty. After comparing the short-term cardiovascular effects of low-speed walking versus high-speed walking for 3 kilometers (km) (3 km/h versus 6 km/h) in young, healthy volunteers, we delivered low-speed walking (low-intensity walking, 2.5 metabolic equivalents of task, METs) as exercise therapy in 42 prehypertensive and 43 hypertensive subjects. We found that one session of 3 km low-intensity walking exerted a transient pressure-lowering effect as well as a mild negative chronotropic effect on heart rate in both the prehypertensive and hypertensive subjects; these short-term benefits on blood pressure and heart rate were accompanied by a brief increase in urine β-endorphin output. Then we prescribed regular low-intensity walking with a target exercise dose (exercise volume) of 500-1000 METs·min/week (50-60 min/day and 5-7 times/week) in hypertensive subjects in addition to their daily activities. Regular low-intensity walking also showed mild but significant blood pressure-lowering and heart rate-reducing effects in 7 hypertensive subjects within two months. It is hypothesized that regular low-intensity exercise of the necessary dose could be taken as a pragmatic and supplementary medication for hypertension management.

Topics: Adult; Aged; beta-Endorphin; Blood Pressure; Exercise Therapy; Female; Heart Rate; Humans; Hypertension; Male; Middle Aged; Prehypertension; Walking

Opioids/opiates are commonly administered to alleviate pain, unload the heart, or decrease breathlessness in patients with advanced heart failure. As such, it is important to evaluate whether the myocardial opioidergic system is altered in cardiac disease. A hamster model of spontaneous hypertension was investigated before the development of hypertension (1 mo of age) and in the hypertensive state (10 mo of age) to evaluate the effect of prolonged hypertension on myocardial opioidergic activity. Plasma beta-endorphin was decreased before the development of hypertension and in the hypertensive state (P < 0.05). There was no change in cardiac beta-endorphin content at either time point. No differences were detected in cardiac or plasma dynorphin A, Met-enkephalin, or Leu-enkephalin, or in cardiac peptide expression of kappa- or delta-opioid receptors. mu-Opioid receptor was not detected in either model. To determine how hypertension affects myocardial opioid signaling, the ex vivo work-performing heart was used to assess the cardiac response to opioid administration in healthy hearts and those subjected to chronic hypertension. Agonists selective for the kappa- and delta-opioid receptors, but not mu-opioid receptors, induced a concentration-dependent decrease in cardiac function. The decrease in left ventricular systolic pressure on administration of the kappa-opioid receptor-selective agonist, U50488H, was attenuated in hearts from hamsters subjected to chronic, untreated hypertension (P < 0.05) compared with control. These results show that peripheral and myocardial opioid expression and signaling are altered in hypertension.

Topics: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Animals; Antihypertensive Agents; Benzamides; beta-Endorphin; Blood Pressure; Cricetinae; Cyclic AMP; Disease Models, Animal; Dynorphins; Enkephalin, Leucine; Enkephalin, Methionine; Hypertension; Hypertrophy, Left Ventricular; Myocardial Contraction; Myocardium; Piperazines; Receptors, Opioid, delta; Receptors, Opioid, kappa; Systole; Ventricular Remodeling

We and others have demonstrated that impaired arterial baroreceptor reflex (ABR) function is one of the major causes of hypertension-associated end organ damage. The goal of this study was to clarify the potential neuro-humoral mechanisms responsible for impaired ABR-induced end organ damage. The sino-aortic denervated (SAD) rat was used as an animal model of ABR dysfunction. One-week SAD rats were characterized by hypertension, tachycardia, increased norepinephrine content, and decreased beta-endorphin and leu-enkephalin content in hypothalamus and medulla oblongata, and increased plasma levels of arginine-vasopressin. In 18-week SAD rats, the 24-hour average arterial pressure, heart rate, beta-endorphin, and leu-enkephalin content in hypothalamus and medulla oblongata and plasma levels of arginine-vasopressin and angiotensin II were not different from those measured in ABR-intact rats. However, blood pressure variability and angiotensin II content in kidney and left ventricle increased. When exposed to chronic stress, exaggerated changes in arterial pressure, blood pressure variability, the levels of central norepinephrine, beta-endorphin and leu-enkephalin, plasma arginine-vasopressin and angiotensin II, and tissue angiotensin II were found in 18-week SAD rats. These data indicate that a long-term impairment of ABR leads to chronic activation of central noradrenergic neurons and tissue renin-angiotensin system, and that stress induces exaggerated responses of neuro-humoral factors and hemodynamics in SAD rats. Thus, if the present results hold true for humans, one can expect abnormal neurotransmitter/neuromodulator responses to environmental insults in patients with impaired ABR function.

Topics: Angiotensin II; Animals; Arginine Vasopressin; Baroreflex; beta-Endorphin; Blood Pressure; Brain; Chronic Disease; Denervation; Enkephalin, Leucine; Heart Rate; Hypertension; Male; Norepinephrine; Radioimmunoassay; Rats; Rats, Sprague-Dawley; Sinoatrial Node

Obesity and high fat diets are associated with an increased prevalence of diabetes, cardiovascular disease, and hypertension. However, the mechanism(s) linking obesity and high fat diet to these metabolic and cardiovascular disorders are not fully elucidated. Leptin stimulates the formation of pro-opiomelanocortin and its products. The stimulation of the central nervous system (CNS) opioids and their receptors is associated with an increase in cardiovascular dynamics. In this study we hypothesized that obesity changed the CNS opioids and their receptors that could play a role in altered cardiovascular and autonomic nervous regulation in obesity. Male Wistar rats were fed either a high fat (HF) or regular chow (control) diet. After 12 weeks, rats were anesthetized and instrumented to record mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA). A blood sample was collected and plasma glucose, insulin, leptin, beta-endorphins were measured. The brains were subsequently processed for immunohistochemistry and in situ hybridization. The HF rats were larger and had a greater percentage of body fat. Leptin and insulin levels were also higher in the HF animals. Basal MAP and RSNA were significantly higher in HF rats. Additionally, immunohistochemistry and in situ hybridization demonstrated that HF rats had increased hypothalamus mu opioid receptors compared to controls. These studies suggest that HF feeding is associated with increased body fat, plasma leptin, insulin, and hypothalamic mu opioid receptors. The increased mu opioid receptors may contribute to the higher MAP and RSNA observed in HF animals.

Topics: Animals; Arteries; beta-Endorphin; Dietary Fats; Food, Formulated; Hypertension; Hypothalamus; Immunohistochemistry; Insulin; Kidney; Leptin; Male; Obesity; Opioid Peptides; Rats; Rats, Wistar; Receptors, Opioid, mu; Sympathetic Nervous System; Vasoconstriction

It has been reported that neuropeptides may play a role in the control of appetite and in the mechanism of hormone release. Neuropeptides such as beta-endorphin, neuropeptide Y (NPY), galanin and leptin may affect hormones release, on the other hand the hormonal status may modulate neuropeptide activity.. The material consisted of 90 obese women, 30 women with Anorexia Nervosa, and 30 healthy, lean women of control group. Plasma beta-endorphin, NPY, leptin, somatostatin and serum pituitary and gonadal hormones concentrations were measured with RIA methods.. We observed the highest plasma NPY levels in obese hypertensive and diabetic patients. After carbohydrate administration (OGTT) a marked increase of insulin, beta-endorphin and NPY was found. The blunted response of GH to GH-RH may be connected with increased somatostatin activity and hyperinsulinemia. The abnormal response of LH to opioid blockade may be a result of disturbed opioid and NPY activities in obese patients. However in patients with anorexia nervosa, plasma leptin and NPY concentrations were low. The disturbances in beta-endorphin release are also observed.. The neuroendocrine disturbances in obesity and in anorexia nervosa are opposite. The feedback mechanism between leptin and NPY is disturbed in both in obesity and in anorexia nervosa. An abnormal activity of neuropeptides may lead to disturbed control of appetite and hormonal dysregulation in eating disorders.

Topics: Adult; Anorexia Nervosa; Appetite; beta-Endorphin; Diabetes Mellitus; Feedback, Physiological; Female; Glucose Tolerance Test; Human Growth Hormone; Humans; Hypertension; Leptin; Luteinizing Hormone; Neuropeptide Y; Neuropeptides; Obesity; Somatostatin

Recent studies have suggested an involvement of the endogenous opioid system in blood pressure control. The purpose of the present study was to determine the role of beta-endorphin in the regulation of sympathetic nervous activity in the central nervous system of hypertension. The effects of beta-endorphin on the electrically evoked release of [3H]norepinephrine (NE) were investigated in superfused slices of rat medulla oblongata. Beta-endorphin inhibited the stimulation-evoked NE release in a dose-dependent manner in rat medulla oblongata. In the medulla oblongata of spontaneously hypertensive rats (SHR), the inhibitory effect of beta-endorphin on the stimulation-evoked NE release was significantly smaller than in the medulla oblongata of Wistar-Kyoto rats. These results showed that beta-endorphin might reduce NE release in rat medulla oblongata. Furthermore, the lesser inhibitory effect of beta-endorphin on NE release in SHR might suggest that the opioid peptide could be involved in the regulation of central sympathetic nervous activity in hypertension.

Topics: Animals; beta-Endorphin; Electric Stimulation; Hypertension; Male; Medulla Oblongata; Norepinephrine; Rats; Rats, Sprague-Dawley

To investigate the involvement of endogenous opioids in acute increases in blood pressure and their functional relationship with atrial natriuretic factor and endothelin-1, we assessed plasma levels of beta-endorphin, met-enkephalin, dynorphin B, catecholamines, atrial natriuretic factor, and endothelin-1 before and after administration of the opioid antagonist naloxone hydrochloride (8 mg i.v.) in 28 hypertensive patients with a stress-induced acute increase in blood pressure. Ten patients with established mild or moderate essential hypertension and 10 normotensive subjects served as control groups. Opioids, atrial natriuretic factor, and endothelin-I were radioimmunoassayed after chromatographic preextraction; catecholamines were determined by high-performance liquid chromatography with electrochemical detection. Patients with an acute increase in blood pressure (systolic, 203.2 +/- 2.2 mm Hg; diastolic, 108.4 +/- 1.3) had plasma opioid, catecholamine, and atrial natriuretic factor levels significantly (P < .01) higher than hypertensive control patients (systolic pressure, 176.4 +/- 1.0 mm Hg; diastolic, 100.0 +/- 1.4), who had a hormonal pattern similar to that of normotensive subjects (systolic pressure, 123.2 +/- 1.5 mm Hg; diastolic, 75.0 +/- 2.0). Endothelin-1 did not differ in any group. In patients with an acute increase in blood pressure, naloxone significantly (P < .01) reduced blood pressure, heart rate, opioids, catecholamines, and atrial natriuretic factor 10 minutes after administration. Naloxone effects on blood pressure, heart rate, opioids, and catecholamines wore off within 20 minutes. In control groups, naloxone failed to modify any of the considered parameters. Our findings suggest that pressor effects of opioid peptides mediated by the autonomic nervous system during stress-induced acute episodes of blood pressure increase in hypertensive patients.

Topics: Atrial Natriuretic Factor; beta-Endorphin; Blood Pressure; Dynorphins; Endorphins; Endothelin-1; Enkephalin, Methionine; Female; Heart Rate; Humans; Hypertension; Infusions, Intravenous; Male; Middle Aged; Naloxone; Narcotic Antagonists; Norepinephrine; Opioid Peptides; Stress, Physiological; Stress, Psychological

Alterations in central dopaminergic mechanisms in the Spontaneously Hypertensive Rat (SHR) have been previously implicated in the development of the hypertensive phenotype in this rat strain. We have examined the expression and regulation of the dopamine-responsive gene proopiomelanocortin (POMC) in the neurointermediate lobe (NIL) of the pituitary in both SHR and normotensive Wista Kyoto (WKY) rats. Solution hybridization/nuclease protection analysis showed that adult SHR express POMC mRNA in the NIL at approximately 2-4 times the level seen in normotensive WKY controls, associated with a concomitant 2-fold increase in dopamine D2-receptor (D2-R) mRNA expression. Despite the obvious difference in D2-R gene expression, NIL POMC mRNA in both rat strains was regulated in an identical manner following 4 d in vivo bromocriptine or haloperidol treatment. In contrast, though D2-R mRNA expression in the WKY NIL was significantly up-regulated by D2-R blockade with haloperidol, the elevated levels of D2-R mRNA in the NIL of the hypertensive strain were not altered by D2-R antagonism. Following isolation from all hypothalamic input by 5 d in vitro culture, SHR melanotrophs exhibited a 2-3 fold higher rate of beta EP secretion and POMC mRNA expression than melanotrophs derived from normotensive WKY rats, though beta EP secretion was inhibited in a similar fashion by the D2-R agonist quinpirole in both cultures. The current data demonstrate changes in expression of both POMC and D2-R mRNA in the SHR NIL which may be a consequence of altered dopaminergic input and/or alterations in D2-R regulation in this tissue, possibly enabling other factors in addition to dopamine to maintain the NIL of the SHR in a relatively hyperactive state. Whether or not POMC-derived peptides or other factors secreted from the melanotroph cell play any role in the development or maintenance of hypertension in this strain is yet to be established.

Topics: Alternative Splicing; Animals; beta-Endorphin; Bromocriptine; Cells, Cultured; Dopamine Agonists; Dopamine Antagonists; Gene Expression Regulation; Haloperidol; Hypertension; Male; Melanocyte-Stimulating Hormones; Pituitary Gland; Pro-Opiomelanocortin; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Receptors, Dopamine D2; RNA, Messenger

Brief (7-14 days) social deprivation stress has been found to increase blood pressure in Wistar rats, an effect dependent on activation of opioid function. The role of central opioids in this and other responses to stress has been repeatedly determined, but the possible involvement of modifications of peripheral opioid mechanisms is poorly understood. To further increase this knowledge, we have examined the opioid sensitivity of tail arteries taken from social deprived Wistar rats by studying the effect of beta-endorphin and DADLE "in vitro". Both opioids inhibited the electrically-induced constriction of the preparations in a dose-dependent manner, but these actions were significantly attenuated after 7-14 days of social deprivation. When the rats were isolated for 30-35 days, the hypertensive response was still present but the arteries from group-housed and isolated animals no longer showed differential sensitivity to opioids. This difference with respect to 7-14 days of isolation could be related to age-dependent changes of opioid function, which were observed among group-housed animals. The results suggest that social deprivation stress induces an adaptation of the tail arteries to the opioid effects on contractility. It is suggested that this endogenous adaptation could be contributing to the hypertensive response observed after social deprivation.

Topics: Adaptation, Physiological; Animals; beta-Endorphin; Dose-Response Relationship, Drug; Enkephalin, Leucine-2-Alanine; Hypertension; Male; Naloxone; Narcotic Antagonists; Narcotics; Rats; Rats, Wistar; Receptors, Opioid; Social Isolation; Stress, Physiological; Tail; Vasoconstriction

Indications for treatment at the Misasa Hot Spring, a radon producing radioactive spring, include hypertension, diabetes mellitus and pain. To clarify its mechanisms of action on these conditions, we evaluated dynamic changes in blood components such as vasoactive substances after radon inhalation. Vasodilation, alleviation of diabetic symptoms and morphine-like analgesic effects were observed, suggesting that these changes constitute part of the mechanisms of the radon spring therapy on the above conditions.

Topics: Administration, Inhalation; Animals; beta-Endorphin; Brachytherapy; Diabetes Mellitus, Experimental; Enkephalin, Methionine; Glucosephosphate Dehydrogenase; Hypertension; Neuropeptides; Pain Management; Rabbits; Radon; Vasodilation

The aims of this study were to determine whether hypertensive patients showed increased endogenous opioid tone and to find a possible correlation between beta-endorphin levels and 24-h ambulatory blood pressure. We also investigated whether circulating beta-endorphin levels were associated with pain perception at rest.. Experimental studies suggest an involvement of the endogenous opioid system in cardiovascular control mechanisms.. We determined baseline beta-endorphin plasma levels by radioimmunoassay in 81 consecutive subjects (48 hypertensive, 33 normotensive) after a 30-min rest and before 24-h ambulatory blood pressure monitoring. In 72 of 81 subjects with a dental formula suitable for the pulpar test (graded increase of test current -0 to 0.03 mA applied to three healthy teeth), pain perception was also investigated.. Hypertensive patients showed higher beta-endorphin plasma levels than normotensive subjects (p < 0.002). Circulating endogenous opioid levels correlated with 24-h diastolic blood pressure (p < 0.01), whereas the relation with systolic pressure did not reach statistical significance. When 24-h blood pressure recordings were divided into daytime and nighttime values, and blood pressure loads (percent of measurements > or = 140 mm Hg for systolic blood pressure and > or = 90 mm Hg for diastolic pressure) were calculated, a significant correlation was found between beta-endorphin levels and diastolic pressures and load. Similarly, presampling diastolic blood pressure was significantly correlated with beta-endorphin levels. Of the 72 subjects tested, hypertensive patients showed a lower pain sensitivity than normotensive subjects. A positive correlation was found between pain threshold and circulating beta-endorphin levels (p < 0.05).. Sustained arterial pressure is probably involved in the tonic activation of cardiovascular mechanisms linked to endogenous opioid tone. Circulating plasma endorphins may account, at least in part, for the pain perception pattern relating to blood pressure levels at rest.

Topics: Adult; beta-Endorphin; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Dental Pulp; Diastole; Electric Stimulation; Humans; Hypertension; Male; Middle Aged; Pain Threshold; Radioimmunoassay; Reference Values

Alcohol acutely causes vasodilation and hypotension in Orientals. To study the mechanisms responsible for the alcohol-induced blood pressure (BP) reduction, we examined levels of various vasoactive hormones after a single intake of alcohol in twelve Japanese men with mild hypertension. On the alcohol intake day, they consumed 1 ml/kg of alcohol with an evening meal, while on the control day they took an isocaloric control drink. BP and vasoactive hormone levels were determined before and 2 h after intake of the alcohol or the control drink. BP after alcohol ingestion was significantly lower than that before drinking or on the control day. This alcohol-induced hypotension was associated with significant increases in heart rate, plasma catecholamines and plasma renin activity (PRA). The changes in heart rate and plasma noradrenaline were inversely related to the changes in BP. Plasma levels of vasopressin and insulin were lower in the alcohol period than in the control period, but these changes were not correlated with the changes in BP. Levels of aldosterone, cortisol, atrial natriuretic peptide, prostaglandin (PG) E2, 6-keto-PGF1 alpha, beta-endorphin, and cyclic GMP were not significantly different between the alcohol and the control periods. These results suggest that changes in pressor hormones may not contribute to the acute hypotensive effect of alcohol, and that the sympathetic nervous system is activated by the BP reduction. The levels of the depressor hormones measured also appear to play no role in alcohol-induced hypotension.

Topics: Adult; Aged; Atrial Natriuretic Factor; beta-Endorphin; Blood Pressure; Ethanol; Hormones; Humans; Hypertension; Male; Middle Aged; Norepinephrine; Potassium; Renin

In order to investigate the changes of endogenous opiate systems in hypertension and their possible role in the pathogenesis in hypertension, we measured plasma concentrations of beta-endorphin, leucine-enkephalin, neurotension, arginine vasopressin, plasma renin activity and angiotensin II by radioimmunoassay in 60 normal persons and 120 patients with essential hypertension. The results showed that the patient group had lower levels of beta-endorphin and leucine enkephalin (P < 0.001), higher levels of arginine vasopressin, plasma renin activity and angiotensin II (P < 0.01, P < 0.05 and P < 0.05, respectively), and normal level of neurotensin, as compared with those in normal group. Plasma levels of leucine-enkephalin was correlated negatively to the mean artery pressure (r = -0.196, P < 0.05). Plasma level of arginine vasopressin was correlated to the duration of the hypertension (r = 0.216, P < 0.05). After 150 min and 14 days of treatment with clonidine, plasma levels of beta-endorphin, leucine-enkephalin increased significantly (< 0.01) and correlated negatively with the decrease of the mean artery pressure (r = -0.340 and r = -0.436 at 150 min, r = -0.369 and r = -0.441 on the 14th day, respectively, P < 0.01). Plasma renin activity and angiotensin II decreased significantly (P < 0.05 and P < 0.01). Arginine vasopressin and neurotensin did not change significantly. After intravenous administration of opiate antagonist-naloxone, the blood pressure and heart rate increased significantly (P < 0.01). The results suggested that the changes of endogenous opioids may be involved in the pathogenesis of hypertension and in the antihypertensive action of clonidine.

Topics: Angiotensin II; Antihypertensive Agents; Arginine Vasopressin; beta-Endorphin; Blood Pressure; Clonidine; Enkephalin, Leucine; Female; Heart Rate; Humans; Hypertension; Injections, Intravenous; Male; Middle Aged; Naloxone; Narcotic Antagonists; Neurotensin; Renin; Time Factors

A comprehensive study of young patients with early hypertensive disease (HD) has revealed their constitutional personality traits which result at long-term traumatization (in addition to exogenous stresses, there is an intrapersonal conflict) in the autonomic nervous disintegration syndrome, lowered parasympathetic effects in the presence of hypersympathicotonia. There is markedly impaired secretion in the dopaminergic link of the sympathoadrenal system along with a steady-state increase in norepinephrine:dopamine ratio, which may be regarded as a possible marker (a risk factor) of HD progression. The decreased secretion of the antistressors dopamine and beta-endorphin can also make a contribution to the progression of HD and its evolution.

Topics: Adult; beta-Endorphin; Blood Pressure; Diet; Dopamine; Electroencephalography; Hemodynamics; Humans; Hypertension; Male; Norepinephrine; Time Factors

Plasma concentrations of beta-endorphin (beta-EP), leucine enkephalin (LEK), arginine vasopressin (AVP), neurotensin (NT), renin activity (PRA) and angiotensin II (AT-II) were determined before and after the treatment with clonidine in 117 patients with essential hypertension. Before the treatment, the patient group had lower levels of beta-EP and LEK (P < 0.001), higher levels of AVP, PRA and AT-II (P < 0.05-0.01), as compared with those in control group. After 14 days of the treatment, plasma levels of beta-EP, LEK increased significantly (P < 0.001), and correlated negatively with the decrease of the mean artery pressure (r = -0.369 and r = -0.441, respectively, P < 0.01). PRA and AT-II decreased significantly (P < 0.05, P < 0.01). Decrease of AVP level was also observed, but did not reach the statistical significance. NT did not change both before and after the treatment. These data suggest that beta-EP and LEK may be involved in pathogenesis of hypertension and in hypotensive action of clonidine.

Topics: Adult; Aged; beta-Endorphin; Blood Pressure; Clonidine; Enkephalin, Leucine; Female; Humans; Hypertension; Male; Middle Aged; Neuropeptides; Renin

The changes of regulatory peptides in 100 patients with essential hypertension at different stages were studied. Four kinds of peptides in serum were measured by RIA method. The results showed that: (1) neurotensin, P-substances, beta-endorphin and leucine-enkephalin decreased significantly in the group (P < 0.01). (2) the levels of those parameters at different stages of hypertension were decreased in parallel with its severity and the difference between different stages is significant (P < 0.01). (3) norepinephrine showed negative correlation with four kinds of neuropeptides. (4) neurotensin, Beta-endorphin and leucine-enkephalin increased significantly after capton (P < 0.01). The possible mechanism and its clinical significance of the changes of those regulatory peptides in hypertension patients were discussed.

Topics: beta-Endorphin; Captopril; Enkephalin, Leucine; Humans; Hypertension; Neuropeptides; Neurotensin; Norepinephrine

The relationship of age-dependent changes in concentrations of various opioid peptides in the brain and pituitary to the development of hypertension was studied in the spontaneously hypertensive rat (SHR). Normotensive Wistar-Kyoto (WKY) and Sprague-Dawley rats served as controls. Opioids determined were dynorphin A (1-8) [DN-A(1-8)], beta-endorphin (BE) and Met-enkephalin (ME). Three approaches were used: (1) temporal correlations of opioid concentrations with the onset of hypertension in 4-, 8-, 12- and 16-week-old rats; (2) study of opioid changes when hypertension development was prevented with antihypertensive drugs and (3) determination of possible opioid peptide changes in another rat model of hypertension, the deoxycorticosterone acetate (DOCA) + salt model. Opioid peptide concentration differences (SHR/WKY) found were as follows. There were much lower DN-A(1-8) levels in the SHR hippocampus and hypothalamus at all ages studied. At 12 and 16 weeks, coincidently with the onset of hypertension, lower levels of BE were found in the anterior lobe of the pituitary, but there were higher BE and ME levels found in the neurointermediate lobe (NIL). Prevention of hypertension in SHR by 8 weeks of oral therapy with guanethidine and hydralazine reversed the BE and ME changes in the NIL but not in the anterior lobe. There were no brain or pituitary changes in opioid peptide concentrations associated with DOCA-salt hypertension. The results are interpreted as supporting a role for altered concentrations of brain and pituitary opioids in the genesis of SHR hypertension.

Topics: Aging; Animals; beta-Endorphin; Brain; Desoxycorticosterone; Dynorphins; Endorphins; Enkephalin, Methionine; Guanethidine; Hydralazine; Hypertension; Male; Pituitary Gland; Rats; Rats, Inbred SHR; Rats, Inbred Strains; Rats, Inbred WKY

To test the hypothesis that hypertension diminishes pain perception, a study was made that evaluated the relation between arterial blood pressure and thermal pain perception in human subjects. The average mean arterial pressure in all 20 men studied (10 hypertensive, 10 normotensive) proved to be significantly related to both thermal pain threshold (p = 0.05) and tolerance (p = 0.003). The difference between normotensive and hypertensive groups in baseline and posttest plasma levels of beta endorphin was also significant (p = 0.02) and indicated an interaction between endogenous opioids and blood pressure. Other recent studies of hypertension in relation to hypalgesia were also reviewed. An increased pain threshold was found in hypertensive versus normotensive rats. In cats, electrical stimulation of vagal afferent nerves (cardiopulmonary baroreceptors) suppresses nociceptive responses, and both pharmacologic elevation of blood pressure and vascular volume expansion produce antinociception. Together with preliminary findings in human studies, these results indicate an interaction between pain-controlling and cardiovascular regulatory functions that is probably mediated by the baroreceptor system.

Topics: Adult; beta-Endorphin; Blood Pressure; Humans; Hypertension; Male; Nociceptors; Pain; Pain Measurement; Pain Threshold

Hypertension was induced by chronic foot-shock and noise stress in adult male Sprague-Dawley rats. Microinjection of 0.3 microliters (150 mmol) sodium glutamate (Glu) into the nucleus arcuatus (ARC) elicited a significant depressor effect in rats with chronic stress-induced hypertension. The depressor effect induced by excitation of ARC neurons was attenuated significantly by microinjection of 0.3 microliters beta-endorphin antiserum (beta-EPAS) into the dorso-medial periaqueductal gray (PAG) or 0.1 microliters into the area of locus coeruleus (LC) due to blockage of beta-endorphinergic fibres from ARC to PAG or LC.

Topics: Animals; Arcuate Nucleus of Hypothalamus; beta-Endorphin; Hypertension; Immune Sera; Locus Coeruleus; Male; Microinjections; Periaqueductal Gray; Rats; Rats, Inbred Strains; Sodium Glutamate; Stress, Physiological

The aim of this study was to determine the significance of the "coronary factor" in patients with essential hypertension (EH). Electrocardiogram Holter monitoring was performed in 61 patients with EH stage II (according to the World Health Organization criteria). Silent, ie, painless ST-segment depression, was found in 34 patients on whom echocardiography, a treadmill test, and transesophageal pacing were performed. In 21 patients with EH and silent ischemia, the examination included 201Tl stress scintigraphy, coronary angiography, and a platelet aggregation test. In 15 patients, catecholamines and beta-endorphins were obtained in blood samples during silent ischemia. 201Tl scintigraphy showed transient defects of perfusion without clearance abnormalities (group I) and with clearance abnormalities (group II). The patients in group I had more severe left ventricular hypertrophy (LVH) and a significantly higher platelet aggregation response to 0.5 mumol/L adenosine diphosphate; one patient in this group had coronary atherosclerosis. LVH and the platelet aggregation response was less pronounced in the patients in group II, but atherosclerotic lesions of a coronary artery were observed in four patients. In both groups, norepinephrine and beta-endorphin levels were increased during silent episodes of ischemia. The results suggest that there are different pathogenetic mechanisms of coronary insufficiency in patients with EH, a hypertensive heart, and silent ischemia.

Topics: Adult; beta-Endorphin; Cardiac Pacing, Artificial; Catecholamines; Coronary Angiography; Coronary Disease; Echocardiography; Esophagus; Exercise Test; Humans; Hypertension; Male; Middle Aged; Platelet Aggregation; Radionuclide Imaging

The paraventricular hypothalamus regulates autonomic nerve outflow and is innervated with beta-endorphin-immunoreactive nerve terminals. This study examined the effects of beta-endorphin microinjected into the paraventricular hypothalamus on blood pressure, heart rate, and plasma catecholamine and glucose concentrations in conscious, unrestrained spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats at the age of about 9 weeks. Thirty minutes after paraventricular hypothalamic injection of [125I] beta-endorphin (3.5 micrograms), most of the recovered radioactivity was detectable within +/- 0.5 mm from the injection site in the coronal, sagittal, and horizontal planes. Unilateral paraventricular hypothalamic injections of beta-endorphin (1 and 0.1 microgram/0.1 microliter) increased blood pressure and heart rate in both strains in a dose-independent manner with significantly greater increases in SHR. Plasma catecholamine and glucose concentrations were measured 15, 30, and 60 minutes after beta-endorphin injection. Norepinephrine concentrations were not significantly altered in WKY rats but increased in SHR. Epinephrine concentrations increased in both strains with significantly greater increases in SHR. Increases in catecholamine concentrations were not dose-related. Glucose concentrations also increased in both strains with significantly greater increases in SHR only at the lower dose. Ganglionic blockade with pentolinium significantly reduced beta-endorphin-induced pressor and tachycardiac responses in SHR. Pretreatment of the paraventricular hypothalamus with naltrexone (1.1 micrograms) in SHR blocked the initial pressor and tachycardiac responses to beta-endorphin (0.1 microgram) and blunted increases in epinephrine and glucose levels. When the animals were anesthetized with alpha-chloralose 2-5 days after the study in conscious animals, there were no differences in blood pressure or heart rate between strains after beta-endorphin (0.1 microgram) injection. The results indicate that conscious SHR show enhanced cardiovascular and sympathoadrenal responses to beta-endorphin injected into the paraventricular hypothalamus, suggesting that alterations in the activity of the paraventricular hypothalamic beta-endorphin system can modulate the development of hypertension in SHR.

Topics: Animals; Behavior, Animal; beta-Endorphin; Blood Glucose; Blood Pressure; Catecholamines; Diffusion; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Enkephalins; Heart Rate; Hypertension; Male; Naltrexone; Paraventricular Hypothalamic Nucleus; Rats; Rats, Inbred SHR; Rats, Inbred WKY

Among 436 patients with hypertension unrelated to any renal lesion, renovascular damage, pheochromocytoma, Cushing's syndrome or hyperthyroidism, 15 patients had low plasma renin activity (PRA) and elevated plasma aldosterone concentrations in the upright position and resultant high aldosterone/PRA ratios: 8 with aldosterone-producing adenoma (APA; group 1) and 7 with idiopathic hyperaldosteronism (IHA; group 2). Thirty-nine patients had suppressed PRA in the presence of normal plasma aldosterone levels and moderately elevated aldosterone/PRA ratios (group 3). Thirty of them had elevated plasma 11-deoxycorticosterone (DOC) and 18-hydroxy-11-deoxycorticosterone (18-OH-DOC) concentrations (group 3a) and 9 of them had normal levels of those mineralocorticoids (group 3b). The rest of them (382 patients) had low aldosterone/PRA ratios (group 4). Adrenal scintigraphy with dexamethasone pretreatment revealed [13I]-cholesterol accumulation not only in patients with APA (unilateral) or IHA (bilateral), but also in patients of group 3a (bilateral). In patients in groups 3a and 3b adrenal size (especially thickness), as measured by computed tomography (CT scan), was enlarged, as in patients with IHA (group 2), and was significantly greater than in patients of group 4 (p less than 0.001). Spironolactone reduced blood pressure in all tested patients of group 3a, and the removal of adrenal tumor or hyperplastic tissue normalized blood pressure in patients of groups 1, 2 and 3a. Excised adrenal glands exhibited cortical hyperplasia with or without nodular hyperplasia in patients of group 3a. Good agreement was found between the actual size of the excised tissue and the measurement obtained by CT scan. Since beta-endorphin and beta-lipotropin were depressed in patients of group 3a, it is suggested that an unknown pituitary substance stimulates the adrenal cortex to release too large amounts of DOC and 18-OH-DOC and inappropriate secretion of aldosterone.

Topics: 18-Hydroxydesoxycorticosterone; Adrenal Glands; Adrenocortical Hyperfunction; Adult; Aged; Aldosterone; beta-Endorphin; beta-Lipotropin; Blood Pressure; Desoxycorticosterone; Female; Humans; Hyperplasia; Hypertension; Male; Middle Aged; Renin; Tomography, X-Ray Computed; Zona Glomerulosa

The role of a high CRH level in normal pregnancy remains unknown. Therefore we evaluated the concentrations of CRH and the related hormones in patients with pregnancy-induced hypertension. Fourteen women with pregnancy-induced hypertension, aged 20-39, at 30-39 gestational week, were investigated. The control group consisted of 20 healthy pregnant women matched according to gestational age. Plasma CRH beta-endorphin-like immunoreactivity, cortisol, and human placental lactogen were measured by radioimmunoassay, ACTH by an immunoradiometric method. It was found that in hypertensive patients the mean CRH concentration was significantly higher (4257 +/- 840 (SEM) ng/l) than that in healthy pregnant women (1083 +/- 227 ng/l, p less than 0.001). The concentration of ACTH, however, was only slightly higher 65.0 +/- 6.0 vs 50.7 +/- 2.5 ng/l p less than 0.025, whereas the differences in beta-endorphin, cortisol and human placental lactogen were not significant. In both groups there was no correlation between the CRH level and those of the related hormones. In healthy pregnant women the CRH level closely correlated with gestational age (r = 0.76, p less than 0.001), whereas in patients with hypertension no such correlation was present (r = 0.29). We assume that the marked enhancement of plasma CRH in pregnancy-induced hypertension is probably caused by its decreased breakdown in ischemic placental tissue, but its increased synthesis in the placenta and its indirect counterregulatory hypotensive role must also be considered.

Topics: Adult; beta-Endorphin; Corticotropin-Releasing Hormone; Female; Gestational Age; Humans; Hydrocortisone; Hypertension; Immunoradiometric Assay; Placental Lactogen; Pregnancy; Pregnancy Complications, Cardiovascular; Radioimmunoassay

Topics: Animals; beta-Endorphin; Cardiovascular System; Hypertension; Injections, Intraventricular; Male; Oligopeptides; Opioid Peptides; Rats; Respiratory System; Synaptic Transmission

Beta-endorphin (B-Ep), ACTH plasma levels and cortisol serum levels have been evaluated by RIA, in 27 patients suffering from essential blood hypertension and in 20 healthy control subjects. The study was repeated in the hypertensive group after clonidine treatment for 15 days. B-Ep plasma levels were normal in the I stage of hypertension and did not show any significant difference in relation to the severity and duration of hypertension. ACTH and cortisol circulating levels in the hypertensive patients were in normal range. The increase of B-Ep plasma levels in the II and III stage of the hypertension is not modified by the reduction of blood pressure values; therefore it is unlikely linked to the elevated blood pressure, but probably to the vascular complications. Moreover, the results obtained after clonidine treatment seem to exclude that the hypotensive action of the drug is mediated by increment of B-Ep circulating levels.

Topics: Adrenocorticotropic Hormone; Adult; Aged; beta-Endorphin; Blood Pressure; Chronic Disease; Clonidine; Drug Evaluation; Female; Humans; Hydrocortisone; Hypertension; Male; Middle Aged

To further study the relationship between endogenous opioid peptides and essential hypertension, we measured the concentrations of plasma leucine-enkephalin (LEK) and beta-endorphin (beta-EP) in 50 patients with essential hypertension by radioimmunoassay and investigated the effects of captopril on them. It was shown that the concentrations of plasma LEK and beta-EP in patients with essential hypertension were lower than those in normotensive subjects. No effects of age and sex were found on the concentrations of plasma LEK and beta-EP, and there was no difference in plasma LEK and beta-EP levels between patients with Stage I essential hypertension and those with Stage II essential hypertension. After a single dose of captopril, blood pressure and plasma angiotensin II decreased, plasma renin activity increased; and plasma LEK and beta-EP levels increased. Plasma LEK and beta-EP levels in patients with essential hypertension increased after one month of captopril treatment. In conclusion, the lower plasma LEK and beta-EP levels in patients with essential hypertension indicate that LEK and beta-EP may play a role in the pathogenesis of essential hypertension, and the depressor effects of captopril may act through LEK and beta-EP, besides blocking formation of angiotension II.

Topics: Adult; Aged; beta-Endorphin; Captopril; Enkephalin, Leucine; Female; Humans; Hypertension; Male; Middle Aged

Research suggests that heightened cardiovascular and neuroendocrine (typically catecholamine) responses to stressors may lead to the development of hypertension and that there may be race differences in patterns of reactivity that are potentially pathogenic. Certain neuropeptides exert profound effects on blood pressure (BP) and heart rate (HR), yet no published studies have examined relationships between these peptides, hypertensive status, race, and reactivity. Seventeen Black and 20 White normotensive and borderline-hypertensive male 19- to 50-year-olds underwent intravenous catheterization while cardiovascular and neuropeptide responses to the stress of being catheterized were examined. Results indicate that, in response to the stressor, Black hypertensives, showed significantly lower endorphin levels compared to Black normotensives, and White hypertensives showed significantly higher levels of beta-endorphin compared to White normotensives. Groups were not significantly different in endorphin levels at recovery. Black hypertensives also showed significantly higher stressor-induced HR and systolic and diastolic BP compared to White hypertensives and normotensives. Lower levels of beta-endorphin and lower urine sodium excretion were associated with higher BP and HR.

Topics: Adult; Arousal; beta-Endorphin; Black People; Blood Pressure; Catheters, Indwelling; Heart Rate; Humans; Hypertension; Male; Middle Aged; Stress, Psychological

Endogenous opioid regulation of blood pressure is altered during stress in young adults at risk for hypertension. We studied the effects of the opioid antagonist naloxone on the secretion of corticotropin and beta-endorphin during psychological stress in young adults with mildly elevated casual arterial pressures. Naloxone-induced secretion of both corticotropin and beta-endorphin was significantly diminished in persons at enhanced risk for hypertension compared with the low blood pressure control group. Results suggest that opioidergic inhibition of anterior pituitary function is altered in hypertension development.

Topics: Adolescent; Adrenocorticotropic Hormone; Adult; beta-Endorphin; Blood Pressure; Epinephrine; Humans; Hydrocortisone; Hypertension; Male; Naloxone; Stress, Psychological

In order to evaluate the role of beta-endorphin in the pathogenesis of obesity and essential hypertension 44 subjects were investigated: 12 nonobese hypertensives, 11 obese hypertensives, 11 obese normotensives and 10 normal subjects. Plasma concentrations of beta-endorphin and cortisol were measured by radioimmunological and ACTH by immunoradiometric methods. The plasma concentrations and the circadian rhythms of ACTH and cortisol secretion were normal in all groups investigated. A circadian rhythm of beta-endorphin secretion was demonstrated in nonobese hypertensives and in normal subjects. The plasma concentrations of beta-endorphin were twice higher than those in nonobese subjects. Also, in all obese patients the circadian rhythm of beta-endorphin secretion was blunted. The increased concentrations and the altered circadian rhythm of beta-endorphin in all obese subjects may point to a role of beta-endorphin in the pathogenesis of obesity rather than in that of essential hypertension.

Topics: Adrenocorticotropic Hormone; Adult; beta-Endorphin; Circadian Rhythm; Humans; Hydrocortisone; Hypertension; Obesity

To investigate the possible release of beta-endorphins (beta EN) from tumors and to investigate their possible involvement in the hypotensive mechanism of clonidine (CLO) in pheochromocytoma (PHEO), as compared with essential hypertension (EH), we studied 12 patients with PHEO, 17 patients with uncomplicated stable EH (SEH), nine patients with borderline EH (BEH), and seven healthy volunteers (N). All subjects were hospitalized and excreted normal amounts of sodium. Mean blood pressure (MAP) and plasma beta EN, norepinephrine (NE), epinephrine (E), and dopamine (DA) were measured before and 180 min after an oral dose of 0.3 mg CLO. Following CLO, a significant (p less than 0.01) decrease in MAP was present in all groups. Plasma NE and E decreased (p less than 0.02 to p less than 0.01) in N, BEH, and SEH, but not in PHEO. DA did not change in any group. Pretreatment beta EN did not differ significantly between the groups, and following CLO it did not change in N or PHEO, while it increased significantly in BEH (p less than 0.01) and in SEH (p less than 0.02). Absolute changes in MAP correlated with those of beta EN only in the SEH group. Changes in NE or E did not correlate with changes in MAP in either group. Likewise, changes in NE or E were not correlated with those of beta EN, in N or EH, but a correlation between resting plasma E and resting beta EN concentrations was demonstrated in PHEO. These results support a role of beta EN in the hypotensive action of CLO in EH, but not in N or PHEO.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adrenal Gland Neoplasms; Adult; beta-Endorphin; Blood Pressure; Catecholamines; Clonidine; Dopamine; Female; Humans; Hypertension; Male; Middle Aged; Neurotransmitter Agents; Pheochromocytoma; Time Factors

Opioid peptides are thought to be involved in blood pressure regulation, possibly via an interaction with the sympathetic nervous system (CNS). To further elucidate this hypothesis the plasma concentrations of beta-endorphin, leucine-enkephalin and noradrenaline were determined overnight (9 p.m. to 8 a.m.) in young patients with mild essential hypertension and then compared to normotensive controls. The mean concentrations of beta-endorphin during the early night (9 p.m. to 2 a.m.) and leucine-enkephalin were lower (p less than 0.05, p less than 0.01, respectively) than in the normotensive subjects, but the noradrenaline concentration was higher. After 14 days of treatment with clonidine, which decreases sympathetic activity via a central action, beta-endorphin, leucine-enkephalin, and noradrenaline concentrations did not differ between both groups. It is concluded that the lower plasma concentrations of beta-endorphin and leucine-enkephalin in the hypertensive group could reflect reduced opioidergic activity in the CNS and in the peripheral sympathetic neurons and also could be involved in the increased sympathetic activity of these patients. Besides via sympathetic inhibition, clonidine also may reduce the increased blood pressure further by normalizing central beta-endorphin release.

Topics: Adult; beta-Endorphin; Blood Pressure; Clonidine; Enkephalin, Leucine; Humans; Hydrocortisone; Hypertension; Male; Norepinephrine; Radioimmunoassay; Renin

The purpose of this study was to evaluate the effect of clonidine--an alpha 2-adrenergic agonist--and naloxone--an opiate antagonist--on pituitary hormone release. The study involved 43 women: 20 menopausal women, 9 untreated women with ACTH-dependent Cushing's disease, and 14 healthy women. Serum GH, ACTH, LH, FSH, TSH, cortisol, and plasma beta-endorphin concentrations were measured with RIA methods. A significant increase in GH and a significant decrease in ACTH and in cortisol was observed after clonidine injection in healthy women. Clonidine caused a significant decrease in LH concentration in the luteal phase of the menstrual cycle. However, naloxone induced the opposite effect on pituitary hormone release. In Cushing's disease, ACTH significantly decreased in response to clonidine. In postmenopausal women with hypertension a decrease in blood pressure, a marked decrease in the number of hot flashes, as well as a diminution in amplitude and frequency of LH pulsatility was found. Conclusions are as follows: (1) Clonidine may be useful in the treatment of hypertensive menopausal women; and (2) a diminution in ACTH, beta-endorphin, and cortisol release in response to clonidine was observed in Cushing's disease.

Topics: Adrenocorticotropic Hormone; Adult; beta-Endorphin; Clonidine; Cushing Syndrome; Female; Growth Hormone; Humans; Hydrocortisone; Hypertension; Luteinizing Hormone; Menopause; Middle Aged; Naloxone; Pituitary Gland, Anterior; Pituitary Hormones, Anterior

The cardiovascular effects of beta-endorphin [beta-LPH-(61-91)] were investigated after systemic (i.v.) and central (third ventricle and right lateral ventricle) administration in urethane-anesthetized rats. beta-Endorphin (10 and 100 micrograms/kg i.v. or 40 micrograms into the third ventricle or into the lateral ventricle) in normotensive animals induced a decrease in blood pressure and bradycardia. The same dose of beta-endorphin by systemic and central administration induced much more pronounced cardiovascular effects in spontaneously hypertensive rats and in rats rendered hypertensive by DOCA administration than in normotensive rats. Naloxone i.v. pretreatment reduced the cardiovascular effects induced by beta-endorphin.

Topics: Animals; beta-Endorphin; Blood Pressure; Desoxycorticosterone; Endorphins; Heart Rate; Hemodynamics; Hypertension; Injections, Intravenous; Injections, Intraventricular; Male; Rats; Rats, Inbred SHR

The relationship between the centrally mediated hypotensive and bradycardic effects of clonidine to central alpha-2 adrenergic receptor activation, brain beta-endorphin (BE) release and opiate receptor activation was studied in chloralose-anesthetized spontaneously hypertensive rats (SHRs) and Wistar-Kyoto rats, using a cerebroventricular perfusion system. Prior treatment of SHRs with i.v. naloxone (2 or 4 mg/kg) or i.c.v. yohimbine (10 or 20 micrograms/kg) reduced the hypotension and bradycardia induced by i.c.v. clonidine, but in Wistar-Kyoto rats naloxone had no similar blocking effects. Prazosin (20 micrograms/kg i.c.v.) reduced the clonidine bradycardia but not the hypotension in SHRs. Hypotension in the SHRs due to i.c.v. alpha-methylnorepinephrine (20 micrograms/kg) was reduced by both naloxone and yohimbine whereas alpha-methylnorepinephrine bradycardia was reduced by yohimbine but not by naloxone. Prior hypothalamic lesions in the SHRs reduced clonidine hypotension, but not bradycardia, and interfered with naloxone blockade of the residual clonidine hypotensive effect. Clonidine lowered immunoreactive BE levels in SHR hypothalamus, medulla and pituitary but did not change BE levels in the i.c.v. perfusate. The findings support the idea that in the SHRs, clonidine hypotension results from alpha-2 adrenergic stimulation of brain, causing BE release and central opiate receptor activation, and they suggest that the hypothalamus is involved in these interactions. Also, clonidine hypotension and bradycardia appear to involve different mechanisms in brain.

Topics: Animals; beta-Endorphin; Blood Pressure; Brain; Clonidine; Endorphins; Heart Rate; Hypertension; Hypothalamus; Male; Naloxone; Prazosin; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Receptors, Adrenergic, alpha; Receptors, Opioid; Yohimbine

The interaction between clonidine and opiate receptor antagonists on arterial blood pressure (BP) and heart rate were examined in normotensive Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR). In conscious SHR, the hypotension and bradycardia caused by clonidine, 5 micrograms/kg iv, were significantly attenuated by naltrexone, 2 mg/kg ip. In urethane-anesthetized SHR, the reduction in mean BP and heart rate in response to 5 nmol clonidine microinjected into the nucleus of the solitary tract (NTS), were similarly inhibited after intra-NTS microinjection of 100 ng DL-naloxone but not after the same dose of D-naloxone. Neonatal treatment of SHR by monosodium glutamate (MSG) markedly reduced the beta-endorphin (BE) but not the leucin-enkephalin content of the arcuate nucleus and the NTS. MSG treatment did not affect the basal BP of these animals, but significantly reduced the hypotensive effect of clonidine and eliminated its susceptibility to opiate antagonists in both conscious and anesthetized SHR. In conscious and anesthetized WKY, the cardiovascular effects of clonidine were smaller than in SHR and were unaffected by naloxone or naltrexone. Neonatal treatment of WKY with MSG reduced the BE content of the arcuate nucleus but not of the NTS. MSG treatment of WKY did not influence either basal BP or the cardiovascular effects of clonidine, and the latter remained unaffected by opiate antagonists. These findings support the hypothesis that in SHR, but not in WKY, the centrally mediated cardiovascular effects of clonidine are partially mediated by the release of a BE-like opioid. They also strongly suggest that the site of both the release and the action of this opioid is in the NTS.

Topics: Animals; Animals, Newborn; Arcuate Nucleus of Hypothalamus; beta-Endorphin; Blood Pressure; Clonidine; Endorphins; Enkephalin, Leucine; Glutamates; Heart Rate; Hemodynamics; Hypertension; Medulla Oblongata; Naloxone; Naltrexone; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Sodium Glutamate

The involvement of endogenous opioid peptides in the antihypertensive action of acutely administered clonidine, a centrally acting adrenergic agonist, was studied in humans. Eight hypertensive subjects received clonidine 0.2 mg orally, naloxone 8 mg i.v. followed by a 0.13 mg/min infusion, and both drugs together on separate days. Clonidine resulted in a significant decrease in mean blood pressure, which was not affected by concomitant treatment with naloxone. Naloxone alone or with clonidine caused significant elevations in plasma aldosterone, not mediated by increased plasma renin activity. Plasma beta-endorphin was not increased after clonidine administration. In humans, the antihypertensive effects of acute clonidine administration do not appear to be mediated by the release or action of endogenous opioids.

Topics: Adult; Aged; Aldosterone; beta-Endorphin; Blood Pressure; Clonidine; Endorphins; Humans; Hypertension; Male; Middle Aged; Naloxone; Renin

Topics: Behavior; beta-Endorphin; Cardiovascular System; Endorphins; Humans; Hypertension; Memory, Short-Term; Nervous System; Pituitary-Adrenal System; Stress, Physiological

In young men with mild essential hypertension and age-matched normotensive volunteers, plasma concentrations of the endogenous opioid beta-endorphin were determined hourly from 9:00 p.m. to 2:00 a.m. The hypertensive patients' mean plasma beta-endorphin concentration was significantly lower in comparison with normotensive controls. After 14 days of treatment with clonidine, systolic and diastolic blood pressure was significantly reduced in both groups. Plasma beta-endorphin concentration increased in the hypertensive patients, but remained unchanged in the normotensive volunteers. The present findings point to a possible involvement of reduced beta-endorphinergic activity in blood pressure regulation of young men with essential hypertension.

Topics: Adult; beta-Endorphin; Blood Pressure; Clonidine; Endorphins; Humans; Hypertension; Male; Radioimmunoassay

To evaluate the role of endogenous opioid peptides in regulating the blood pressure of hypertensive individuals, we administered the opiate antagonist, naloxone. One individual developed a severe hypertensive response, mean arterial pressure rising from a baseline of 107 mmHg to 147 mmHg 145 min after naloxone injection and infusion. After stopping naloxone, his blood pressure rapidly returned to baseline. Re-challenge with naloxone and clonidine resulted in a modest reduction of blood pressure in contrast to the profound hypotension induced by clonidine alone during a third session. Thus, endogenous opioids appear to regulate blood pressure in some hypertensive patients and opiate antagonists must be administered with caution to these individuals.

Topics: beta-Endorphin; Blood Pressure; Clonidine; Endorphins; Humans; Hypertension; Male; Middle Aged; Naloxone

Excessive production of an as yet unidentified aldosterone-stimulating factor may cause idiopathic hyperaldosteronism (IHA). This putative factor may be related to proopiomelanocortin-derived peptides, some of which have aldosterone-stimulating properties. The present study evaluated plasma beta-endorphin, ACTH, cortisol, and aldosterone levels in patients with IHA (n = 10), aldosterone-producing adenomas (n = 4), essential hypertension (n = 11), and normal subjects (n = 10). Plasma and urinary hormone measurements were obtained at timed intervals during an isocaloric, fixed electrolyte intake (Na+, 128 meq/day; K+, 80 meq/day) in a metabolic unit. Plasma for beta-endorphin assay was preincubated with sepharose-bound anti-beta-lipotropin to remove beta-lipotropin that cross-reacted with the beta-endorphin RIA. Mean +/- SE plasma beta-endorphin levels at 0800 h were elevated in IHA patients (47 +/- 13 fmol/ml) compared to those in aldosterone-producing adenoma (25 +/- 9), essential hypertension (16 +/- 1), and normal control (20 +/- 2; P less than 0.05) subjects. Plasma ACTH, plasma cortisol, and urinary cortisol levels were not different in these four groups. These data support the hypothesis that excess production of either beta-endorphin or related proopiomelanocortin-derived peptides may function as aldosterone secretogogue(s) in IHA.

Topics: 18-Hydroxycorticosterone; Adenoma; Adrenal Cortex Neoplasms; Adrenocorticotropic Hormone; Adult; Aged; Aldosterone; beta-Endorphin; Endorphins; Female; Humans; Hyperaldosteronism; Hypertension; Male; Middle Aged; Posture; Renin

Whether peripheral beta-endorphin contributes to the antihypertensive action of clonidine was examined by measuring plasma levels of beta-endorphin-like immunoreactivity (beta EpLI) after acute administration of clonidine in patients with essential hypertension. Administration of clonidine (0.225 mg) in one dose significantly lowered blood pressure, decreased heart rate and reduced the plasma level of beta EpLI and ACTH, while the placebo had no effect on blood pressure, heart rate or plasma level of beta EpLI suggesting that peripheral beta-endorphin does not play a major role in the antihypertensive action of acute clonidine administration.

Topics: Adrenocorticotropic Hormone; Adult; Aged; beta-Endorphin; Blood Pressure; Clonidine; Endorphins; Female; Heart Rate; Humans; Hypertension; Male; Middle Aged; Receptors, Adrenergic, alpha; Time Factors

Changes in brain neuropeptide content in spontaneously hypertensive rats may be primarily related to the development of hypertension or may be secondary consequences of it. We have measured brain concentrations of beta-endorphin, Leu-enkephalin, arginine vasopressin (AVP) and oxytocin (OXT) in stroke-prone spontaneously hypertensive rats (SHRSP) and in age-matched normotensive Wistar Kyoto (WKY) controls, as well as in SHRSP with normalized blood pressure by chronic treatment with clonidine. Opioid peptide contents were measured in 12-, 18- and 24-week-old rats. beta-Endorphin was measured in the neuro-intermediate and anterior lobes of the pituitary, the hypothalamus, mid-brain and brain stem; Leu-enkephalin in the neuro-intermediate lobe of the pituitary, hypothalamus, mid-brain, brain stem, as well as in the spinal cord and adrenal glands. AVP and OXT were measured in the neuro-intermediate lobe of the pituitary, hypothalamus, brain stem and spinal cord. beta-Endorphin in the neuro-intermediate lobe of the pituitary was significantly higher in 12- and 18-week-old SHRSP. Adrenal gland Leu-enkephalin was lower in SHRSP as compared with the WKY. OXT and AVP contents were markedly reduced in all brain regions of SHRSP except the neuro-intermediate lobe of the pituitary, where no significant changes were found. In no case did long-term antihypertensive treatment with clonidine reverse the altered peptide content in the SHRSP. We conclude that alterations in brain neuropeptide content in SHRSP are not secondary to hypertension. The blood pressure lowering activity of clonidine appears not to depend on major alterations of peptide concentrations. A genetic defect in the synthesis of adrenal enkephalins and hypothalamic OXT and AVP seems likely from these studies.

Topics: Animals; Arginine Vasopressin; beta-Endorphin; Brain; Clonidine; Endorphins; Enkephalin, Leucine; Hypertension; Male; Nerve Tissue Proteins; Oxytocin; Rats; Rats, Inbred SHR; Rats, Inbred WKY

Recent observations suggest that there may be two pools of beta-endorphin-like immunoreactivity in mammalian circulation. One of these pools is present in plasma and the other is detected in association with erythrocytes. Elucidation of an erythrocyte-associated pool may explain some of the wide variability of plasma beta-endorphin levels reported in the literature. We measured beta-endorphin immunoreactivity levels in 85 normal and 33 complicated pregnancies to delineate a possible correlation between gestational age and beta-endorphin immunoreactivity levels in plasma and in erythrocytes. Our results indicate that beta-endorphin immunoreactivity levels in both plasma and erythrocytes vary systematically throughout the gestational period, reaching a peak at 31 to 32 weeks of gestation. Amniotic fluids at midgestation were also analyzed and no correlation was observed between the levels of beta-endorphin immunoreactivity and fetal sex. Compared to normal patients, diabetic patients had significantly lower levels of beta-endorphin immunoreactivity in plasma and higher levels in erythrocytes although the total beta-endorphin immunoreactivity was not statistically different from that in normal subjects. We conclude that (1) the total beta-endorphin immunoreactivity level in whole blood is much higher than that reported in plasma, (2) both plasma- and erythrocyte-associated beta-endorphin immunoreactivity levels vary with gestational age, with a peak level at 24 to 32 weeks of gestation, (3) amniotic fluid beta-endorphin immunoreactivity levels are unrelated to fetal sex, and (4) diabetic patients may have a different distribution of beta-endorphin immunoreactivity pools than normal individuals.

Topics: Amniotic Fluid; beta-Endorphin; Endorphins; Erythrocytes; Female; Gestational Age; Humans; Hypertension; Labor Onset; Plasma; Pregnancy; Pregnancy Complications; Pregnancy in Diabetics; Radioimmunoassay; Sex Determination Analysis

Analysis of the effect of naloxone (0.4 mg iv.) on clonidine hypotension in 80 patients with essential hypertension revealed that two groups could be separated. In the responding group (43 pts) naloxone increased blood pressure and heart rate in clonidine-treated patients while in the non-responding group (37 pts) it has no such effect. Patients in the responding group had higher cardiac output, stroke volume, plasma renin activity, plasma adrenaline and beta-endorphin levels and lower total peripheral resistance, shorter history of hypertension and lesser body weight than those in the non-responding group. The pressor effect of naloxone in four responding patients treated with clonidine for 29 months tended to be smaller compared to the response obtained after a 3-day clonidine therapy. Results favour the hypothesis of the existence of two (responding, non-responding) groups of patients with essential hypertension. Further work will clarify whether these groups represent different pathogenesis or they indicate only a different stage of hypertension.

Topics: Adult; beta-Endorphin; Blood Pressure; Clonidine; Endorphins; Female; Hemodynamics; Humans; Hypertension; Male; Middle Aged; Naloxone; Random Allocation

The hypotensive action of two novel imidazolinic alpha-adrenergic agonists (ICI-106270 and UK-14304) with similar pharmacological properties to clonidine was shown in spontaneously hypertensive (SH) rats. The antihypertensive effect of the clonidine-type agents was prevented by either peripheral administration of the opiate antagonist naloxone or by intracerebroventricular (i.c.v.) injection with a specific antibody against human beta-endorphin (BEN). A dose-response relationship was found for the hypotensive effect of i.c.v. given BEN in SH rats, the low blood pressure being significantly reversed by further treatment with either naloxone or anti-beta h-endorphin. These data confirm and extend the notion of a BEN mediation in the antihypertensive action of clonidine-type alpha-adrenergic agonists in SH rats.

Topics: Animals; Antihypertensive Agents; beta-Endorphin; Blood Pressure; Brimonidine Tartrate; Clonidine; Dose-Response Relationship, Drug; Endorphins; Hypertension; Imidazoles; Injections, Intraventricular; Male; Quinoxalines; Rats

Topics: Adult; beta-Endorphin; Blood Pressure; Clonidine; Endorphins; Female; Heart Rate; Humans; Hypertension; Male; Middle Aged

Naloxone [0.4 mg iv.] increased blood pressure and heart rate of 13 clonidine-treated [0.3 mg per os for 3 days] patients with essential hypertension [reacting group] while it has no such effect in 11 clonidine-treated patients [non-reacting gr.] Clonidine increased plasma beta-endorphin concentration of the reacting patients by 17.53 +/- 1.68 pM/1 and in the non-reacting ones by 5.91 +/- 0.88 pM/1. Significant linear correlation was found between the clonidine-induced increase in plasma beta-endorphin level and the naloxone-induced change in mean blood pressure [r = 0.9572, n:24, p less than 0.001]. In another group of 8 patients clonidine [0.15 mg iv.] decreased mean blood pressure but naloxone, 30 min after the clonidine injection, did not reverse the clonidine hypotension. We suggest that beta-endorphin, released by chr. clonidine therapy, contributes to the anti-hypertensive effect only in the reacting group.

Topics: Adult; beta-Endorphin; Blood Pressure; Clonidine; Drug Interactions; Endorphins; Heart Rate; Humans; Hypertension; Middle Aged; Naloxone

Topics: Adolescent; Adult; beta-Endorphin; Blood Pressure; Endorphins; Enkephalin, Leucine; Enkephalin, Methionine; Female; Humans; Hypertension; Male; Physical Exertion; Veins

Topics: Adrenal Glands; Animals; beta-Endorphin; Blood Pressure; Central Nervous System; Endorphins; Enkephalin, Leucine; Hypertension; Male; Pituitary Gland, Anterior; Rats; Rats, Inbred SHR; Rats, Inbred Strains; Rats, Inbred WKY

Topics: Adolescent; Adult; beta-Endorphin; Dipeptides; Enalapril; Endorphins; Female; Humans; Hypertension; Male; Middle Aged; Propranolol; Renin-Angiotensin System; Sympathetic Nervous System

Male and female, young (2 months old) and mature (10 months old), obese and nonobese, spontaneously hypertensive rats (SHR) were treated with dexamethasone, 5 micrograms/rat and 10 micrograms/rat, respectively, subcutaneously (SC) 2 times daily for 5 months. Steroid treatment stilled the voracious appetite of the obese SHR, and the massively obese, mature animals were reduced to almost normal size. The young, steroid-treated, obese SHR did not develop their genetically programmed corpulency. The untreated, young and mature, obese SHR ate voraciously, became massively obese, and developed their characteristic Cushing's disease-like spectrum of degenerative changes, eg, hypertension, hyperlipidemia, hyperglycemia, muscle wasting, kidney stones, thin skin, and accelerated aging. The blood pressure of the steroid-treated animals was lowered concomitant with reduced levels of circulating ACTH, beta endorphin, insulin, triglycerides, and cholesterol. Dexamethasone caused hyperlipidemia, hyperglycemia, and increased BUN levels in young obese and nonobese SHR only. The mature obese SHR had giant-sized thymus glands that were further enlarged with steroid treatment; dexamethasone was thymolytic in young, obese and nonobese SHR. Dexamethasone caused severe reduction of pituitary and adrenal gland size, simulating the condition of hypophysectomy. These findings demonstrate that dexamethasone suppression of the pituitary-adrenal axis palliates and prevents the spontaneous development of Cushingoid degenerative changes in these genetically obese and hypertensive rats.

Topics: Adrenal Glands; Adrenocorticotropic Hormone; Animals; beta-Endorphin; Blood Glucose; Blood Urea Nitrogen; Cushing Syndrome; Dexamethasone; Disease Models, Animal; Endorphins; Female; Hypertension; Insulin; Lipids; Male; Obesity; Organ Size; Pituitary Gland; Rats; Rats, Inbred Strains

Beta-endorphin and related opioid peptides are neuropeptides which appear to play a role in cardiovascular regulation which is supported by altered nociceptive responsiveness in hypertensive animals. In spontaneously hypertensive rats the pain threshold for electric stimulation is elevated; these rats show increased response latency time in a hot plate test. The opiate antagonist naloxone reverses these values to that of the normotensive controls. In other forms of experimental hypertension, eg, renal hypertension (one-clip, two-kidney model), no change in pain sensitivity is apparent. Sinoaortic baroreceptor denervation causes a labile hypertension without changes in hot plate response. Administration of beta-endorphin into the nucleus of the solitary tract (NTS) gradually decreases blood pressure and heart rate without affecting respiratory frequency. These cardiovascular effects are blocked by naloxone as well as by an antibody to beta-endorphin. In contrast to the effects of beta-endorphin, microinjection of enkephalins into the NTS increases blood pressure and heart rate. The data suggest the existence of two separate endorphin systems at the level of the NTS, one a depressor and another a pressor system. The depressor influence of beta-endorphin may play a role in the mechanism of action of antihypertensive agents such as methyldopa and clonidine. Our data support a role of endorphins as neuropeptides involved in cardiovascular regulation, exerting a dual influence at the level of the NTS.

Topics: Animals; beta-Endorphin; Blood Pressure; Brain; Endorphins; Enkephalins; Heart Rate; Hypertension; Male; Medulla Oblongata; Naloxone; Nociceptors; Pain; Rats; Sensory Thresholds

Diurnal rhythm of plasma beta endorphin was established with the highest level in the morning and the lowest one at midnight in normotensive subjects and also in patients with essential hypertension. Clonidine (300 micrograms daily) significantly increased plasma beta endorphin concentrations only in the hypertensive patients. The significant linear correlation between the increase in plasma beta endorphin concentration and the decrease in blood pressure (both systolic and diastolic) in these patients may point to the role of this endogenous opioid in the antihypertensive action of clonidine.

Topics: beta-Endorphin; Circadian Rhythm; Clonidine; Endorphins; Hemodynamics; Humans; Hypertension

Topics: Animals; beta-Endorphin; Blood Pressure; Clonidine; Desoxycorticosterone; Endorphins; Heart Rate; Hypertension; Hypertension, Renal; Immune Sera; Male; Methyldopa; Naltrexone; Rats; Rats, Inbred Strains; Rats, Mutant Strains

Topics: beta-Endorphin; Clonidine; Endorphins; Heart Rate; Humans; Hypertension; Receptors, Opioid

Topics: Adrenal Glands; Animals; beta-Endorphin; Blood Pressure; Brain; Digestive System; Endorphins; Humans; Hypertension; Morphine; Pain; Pituitary Gland; Receptors, Opioid; Shock

1. Immunoreactive beta-endorphin (IR-beta EP) was two- to three-fold higher in pituitary neuro-intermediate lobes (N-IL) of spontaneously hypertensive rats (SHR) than of normotensive Wistar--Kyoto (NT-WKY) controls. 2. Plasma levels of IR-beta EP were lower in SHR than in NT-WKY rats. 3. Intravenous injections of morphine lowered blood pressure of both SHR and NT-WKY rats to the same level; naloxone restored blood pressure of both groups to pre-morphine values. 4. Infusion of bromocriptine in SHR for 1 week lowered blood pressure and N-IL IR-beta EP concentration. 5. These results confirm and extend postulated dopaminergic defect in this model of hypertension.

Topics: Animals; beta-Endorphin; Blood Pressure; Bromocriptine; Endorphins; Female; Hypertension; Rats; Rats, Inbred Strains