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1.
Pharmacology ; 50(4): 209-17, 1995 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-7792309

RESUMO

This 21-day, open-label study evaluated the effects of raloxifene and tamoxifen on estrogen-induced changes in serum levels of anterior pituitary hormones (prolactin, luteinizing hormone, and follicle-stimulating hormone), sex steroids (testosterone, estradiol), and binding globulins [thyroid binding globulin (T3 resin uptake), transcortin, sex steroid binding globulin]. Seventeen healthy male volunteers completed the study after being randomized to one of three treatments: raloxifene, tamoxifen, or placebo. Six subjects received raloxifene (200 mg daily) for 10 days, 6 subjects received tamoxifen [20 mg twice a day (b.i.d.)] for 10 days, and 5 subjects received placebo for 10 days. All subjects received ethinyl estradiol (20 micrograms b.i.d.) for 7 days starting 3 days after initiation of study drug or placebo treatment. Results of the primary analysis of this study indicate that for six of the seven analyzable parameters of estrogen action (excluding luteinizing hormone) raloxifene blunted the estrogen response; this effect was significant only for T3 resin uptake. Tamoxifen administration significantly blunted or reversed the estrogen effect in all six of these parameters. Raloxifene, an effective antiestrogen in animal models, is also antiestrogenic in humans.


Assuntos
Antagonistas de Estrogênios/farmacologia , Etinilestradiol/antagonistas & inibidores , Piperidinas/farmacologia , Adulto , Análise de Variância , Interações Medicamentosas , Estradiol/sangue , Antagonistas de Estrogênios/efeitos adversos , Hormônio Foliculoestimulante/sangue , Hormônios Esteroides Gonadais/sangue , Humanos , Hormônio Luteinizante/sangue , Masculino , Pessoa de Meia-Idade , Piperidinas/efeitos adversos , Hormônios Adeno-Hipofisários/sangue , Prolactina/sangue , Cloridrato de Raloxifeno , Globulina de Ligação a Hormônio Sexual/metabolismo , Tamoxifeno/farmacologia , Testosterona/sangue , Transcortina/metabolismo
2.
J Clin Psychopharmacol ; 13(5): 312-20, 1993 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-8227489

RESUMO

The primary objective of this article is to review information pertinent to and emphasize the seriousness of a potential adverse monoamine oxidase inhibitor (MAOI)-serotonin uptake inhibitor interaction by considering, within the context of preclinical data, clinical cases in which an MAOI and fluoxetine hydrochloride, a specific serotonin uptake inhibitor, were administered in close temporal proximity. Clinical cases were identified by a review of spontaneous adverse event reports submitted voluntarily to Eli Lilly and Company through its drug surveillance program and by a review of reports of MAOI interactions published in the scientific literature. A discussion of eight selected clinical cases of acute adverse reactions (seven with fatal outcomes; one with a favorable response after cyproheptadine therapy) reported to Eli Lilly and Company in which an MAOI was initiated concurrently or shortly after the discontinuation of fluoxetine and a review of preclinical data suggest a possible role of serotonin and/or serotonin-dopamine interactions in the hypermetabolic state that may occur when a serotonin uptake inhibitor and an MAOI are coadministered, although alternative etiologic processes are possible as well. Data reviewed reinforce the idea that the administration of an MAOI in close temporal proximity to fluoxetine is contraindicated.


Assuntos
Transtorno Depressivo/tratamento farmacológico , Fluoxetina/efeitos adversos , Inibidores da Monoaminoxidase/efeitos adversos , Adulto , Idoso , Encéfalo/efeitos dos fármacos , Encéfalo/fisiopatologia , Transtorno Depressivo/psicologia , Relação Dose-Resposta a Droga , Esquema de Medicação , Interações Medicamentosas , Quimioterapia Combinada , Evolução Fatal , Feminino , Fluoxetina/administração & dosagem , Fluoxetina/farmacocinética , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Monoaminoxidase/administração & dosagem , Inibidores da Monoaminoxidase/farmacocinética , Exame Neurológico/efeitos dos fármacos , Fenelzina/administração & dosagem , Fenelzina/efeitos adversos , Fenelzina/farmacocinética , Vigilância de Produtos Comercializados , Receptores de Serotonina/efeitos dos fármacos , Receptores de Serotonina/fisiologia , Tranilcipromina/administração & dosagem , Tranilcipromina/efeitos adversos , Tranilcipromina/farmacocinética
3.
Neuroreport ; 2(10): 612-4, 1991 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-1756241

RESUMO

Cardiovascular and vasopressin (AVP) responses to hemorrhage were studied in rats with lesions of the hypothalamic supraoptic nuclei (SONL). Bleeding caused hypotension and increase in heart rate (HR) and AVP. SONL rats failed to fully recover from bleeding as compared to normal rats. Plasma AVP in SONL rats was in the normal in basal conditions, but failed to increase to levels attained in normal rats throughout the post-hemorrhage period. These data suggest that the supraoptic nuclei are the primary regulatory sites for AVP release in response to hemorrhage and that lack of adequate AVP release significantly retards blood pressure recovery after bleeding.


Assuntos
Arginina Vasopressina/metabolismo , Pressão Sanguínea , Frequência Cardíaca , Hemorragia/fisiopatologia , Núcleo Supraóptico/fisiopatologia , Animais , Arginina Vasopressina/sangue , Masculino , Ratos , Ratos Endogâmicos , Valores de Referência , Núcleo Supraóptico/fisiologia , Fatores de Tempo
4.
J Lab Clin Med ; 117(1): 51-9, 1991 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-1987308

RESUMO

The rise in plasma vasopressin produced by infusion of hypertonic saline varies widely among healthy adults. To determine if these interindividual differences are reproducible, we used linear regression to analyze the relationship of plasma vasopressin to plasma osmolality during repeat hypertonic saline infusion in seven normal subjects. The results confirmed that the slope or sensitivity of the relationship differed widely between subjects (0.12 to 1.66 pg/ml/mOsm/kg) and revealed that these differences were highly reproducible. (r = 0.94 on repeat testing). The individual values for osmotic threshold were less variable (280 to 288 mOsm/kg) as well as less clearly reproducible (r = 0.61). To determine whether these differences are genetically influenced, we compared the vasopressin osmolality relationships within seven monozygotic and six dizygotic twin pairs. We found that the threshold and sensitivity values correlated significantly within monozygotes (r = 0.95 and 0.95) but not within dizygotes (r = 0.34 and 0.21). When the osmoregulation of thirst was similarly evaluated, the individual relationships were as variable as for plasma vasopressin, but only the threshold values in monozygotes correlated significantly (r = 0.92). In 80 healthy adults, the frequency distributions of the osmotic threshold and sensitivity of the vasopressin responses were essentially normal. We conclude that the sensitivity for vasopressin secretion as well as the osmotic thresholds for thirst and vasopressin demonstrate significant polygenetic variance among healthy adults.


Assuntos
Variação Genética , Equilíbrio Hidroeletrolítico/fisiologia , Adulto , Fenômenos Fisiológicos Sanguíneos , Limiar Diferencial , Feminino , Humanos , Individualidade , Masculino , Concentração Osmolar , Probabilidade , Valores de Referência , Análise de Regressão , Reprodutibilidade dos Testes , Sede/fisiologia , Gêmeos Dizigóticos , Gêmeos Monozigóticos , Vasopressinas/sangue
5.
Circ Shock ; 27(3): 219-35, 1989 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-2650916

RESUMO

We have previously reported that analgesic doses of morphine accelerate mortality of rats exposed to hemorrhage (Feuerstein and Sirén: Circ Shock 19:293-300, 1986). To study the potential mechanisms involved in this phenomenon, rats were chronically implanted with catheters in the femoral vessels and morphine (1.5 or 5 mg/kg) was administered 30 min or 24 hr after bleeding (8.5 ml/300 g over 5 min) while arterial blood pressure and heart rate were continuously monitored. Furthermore, the effect of morphine (5 mg/kg) on cardiac output (CO) response to hemorrhage was studied in rats chronically equipped with a minithermistor for CO monitoring by a thermodilution technique. In addition, plasma catecholamines (HPLC), plasma renin activity (PRA, RIA), vasopressin (RIA), pH, and blood gases were also determined. Morphine administration 30 min after hemorrhage produced a pressor response and tachycardia which were in marked contrast to its depressor effect in intact rats. Morphine elevated PRA and epinephrine but not vasopressin, while blood pH and gases showed no consistent change as compared to saline-treated hemorrhaged rats. Morphine given after the bleeding resulted in enhanced cardiac depression in response to a second bleed of 2 ml/300 g. Our data suggest that activation of pressor mechanisms by morphine during hypovolemic hypotension might enhance vasoconstriction in essential organs, depress cardiac function, and further reduce effective tissue perfusion.


Assuntos
Morfina/farmacologia , Sistemas Neurossecretores/fisiopatologia , Choque Hemorrágico/fisiopatologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Catecolaminas/sangue , Frequência Cardíaca/efeitos dos fármacos , Masculino , Sistemas Neurossecretores/efeitos dos fármacos , Ratos , Ratos Endogâmicos , Renina/sangue , Choque Hemorrágico/metabolismo , Fatores de Tempo , Vasopressinas/sangue
6.
J Pharmacol Exp Ther ; 242(1): 33-9, 1987 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-3039112

RESUMO

Marked diuresis has previously been reported after administration of kappa opioid agonists. The present study shows that this effect is stereospecific; MR-2034 markedly increased urinary output over the dose range 0.08 to 1.25 mg/kg, whereas the opposite isomer, MR-2035, was markedly less potent. Bremazocine increased urinary output in Long-Evans hooded and Sprague-Dawley albino rats as well as lean and fatty Zucker rats. In the lean Zucker and the albino rats, bremazocine produced an inverted U-shaped diuretic dose-effect curve, an effect characteristic of kappa agonists with mu agonist activity. This pattern was not seen with the fatty Zucker rats or the Long-Evans hooded rats. The full kappa agonists bremazocine, ethylketazocine and U-50,488 increased urinary output under three different conditions of hydration: water loaded, normal hydration and water deprived. In contrast, the partial kappa agonists reliably only increase urinary output under the normal hydration condition. The diuretic effects of full and partial kappa agonists correlated with plasma vasopressin levels in water-deprived rats. The full kappa agonists (ethylketazocine, U-50,488, tifluadom and MR-2034) suppressed plasma vasopressin levels below the threshold of detectability of the radioimmunoassay, whereas the partial kappa agonists (nalorphine and butorphanol) suppressed vasopressin levels compared with control values but did not have the efficacy of the full kappa agonists. All these results support the hypothesis that kappa agonists produce their diuretic effect by suppression of plasma vasopressin levels.


Assuntos
Diurese/efeitos dos fármacos , Etilcetociclazocina/análogos & derivados , Receptores Opioides/efeitos dos fármacos , Vasopressinas/sangue , (trans)-Isômero de 3,4-dicloro-N-metil-N-(2-(1-pirrolidinil)-ciclo-hexil)-benzenoacetamida , Animais , Benzomorfanos/farmacologia , Butorfanol/farmacologia , Ciclazocina/análogos & derivados , Ciclazocina/farmacologia , Ingestão de Líquidos , Feminino , Masculino , Nalorfina/farmacologia , Pirrolidinas/farmacologia , Ratos , Ratos Endogâmicos , Ratos Zucker , Receptores Opioides/fisiologia , Receptores Opioides kappa , Estereoisomerismo , Privação de Água/fisiologia
7.
Br J Psychiatry ; 150: 208-12, 1987 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-2888503

RESUMO

Levels of vasopressin, somatostatin, neurotensin, vasoactive intestinal peptide, corticotrophin-releasing factor and adrenocorticotrophin in CSF were determined in lithium-treated and unmedicated euthymic bipolar patients and controls, in a search for a trait marker in affective disorder. No group differences in levels of these peptides were found. Highly significant positive correlations were found among these peptides (with the exception of neurotensin), suggesting that their presence in CSF is functionally significant, as opposed to the result of random diffusion from the interstitial space of the brain.


Assuntos
Transtorno Bipolar/líquido cefalorraquidiano , Neuropeptídeos/líquido cefalorraquidiano , Hormônio Adrenocorticotrópico/líquido cefalorraquidiano , Transtorno Bipolar/tratamento farmacológico , Hormônio Liberador da Corticotropina/líquido cefalorraquidiano , Humanos , Lítio/uso terapêutico , Neurotensina/líquido cefalorraquidiano , Somatostatina/líquido cefalorraquidiano , Peptídeo Intestinal Vasoativo/líquido cefalorraquidiano , Vasopressinas/líquido cefalorraquidiano
8.
Int J Obes ; 11 Suppl 3: 191-9, 1987.
Artigo em Inglês | MEDLINE | ID: mdl-3501995

RESUMO

Observations related to the safety of fluoxetine in the treatment of obese patients are reviewed. The adverse event profile in obese patients, though differing slightly from that seen in depressed patients, was similar in that events observed were generally mild and well tolerated. Other than rash, no potentially serious adverse events believed to be related to fluoxetine were observed. Special evaluations of pharmacokinetics, psychomotor impairment, cardiac effects, phospholipidosis and addiction potential have identified no major problems in these areas. It is concluded that fluoxetine use for the treatment of obesity should carry with it minimal risk.


Assuntos
Fluoxetina/efeitos adversos , Obesidade/tratamento farmacológico , Propilaminas/efeitos adversos , Interações Medicamentosas , Fluoxetina/farmacocinética , Coração/efeitos dos fármacos , Humanos , Lipidoses/induzido quimicamente , Fígado/efeitos dos fármacos , Fosfolipídeos/metabolismo , Desempenho Psicomotor/efeitos dos fármacos , Dermatopatias/induzido quimicamente , Transtornos Relacionados ao Uso de Substâncias
10.
J Gen Intern Med ; 1(6): 380-5, 1986.
Artigo em Inglês | MEDLINE | ID: mdl-3794837

RESUMO

To assess the risk of mortality in patients with hyponatremia at the time of hospital admission, the authors studied data for 13,979 patients admitted over a 46-month period. Of the 763 (4%) admitted with hyponatremia, 757 (99%) were matched by age, gender, and admitting date with normonatremic control patients. Hyponatremic patients were more than seven times as likely to die in the hospital than the control patients, and they were more than twice as likely to die after discharge (p less than 0.0001 for both). This relationship with in- and outpatient mortality held when controlling for the diagnoses found more often in the hyponatremic patients. Hyponatremia appears to be an indicator of increased risk of death regardless of the disease with which it is associated.


Assuntos
Hiponatremia/mortalidade , Admissão do Paciente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Hiponatremia/complicações , Masculino , Pessoa de Meia-Idade , Alta do Paciente , Prognóstico , Análise de Regressão , Estudos Retrospectivos , Risco
11.
Agents Actions ; 18(5-6): 494-8, 1986 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-2429527

RESUMO

There is evidence to suggest that histamine is a neurotransmitter in the CNS and functions in the regulation of arg-vasopressin (AVP) secretion. The posterior pituitary contains high levels of histamine and histamine N-methyltransferase (HNMT). Therefore, posterior pituitary histamine could also modulate the release of AVP. Paralleling the effect on AVP levels, the concentration of histamine in the rat posterior pituitary decreased from 18.8 +/- 2.7 ng/mg protein (x +/- SEM) to 12.9 +/- 1.9 ng/mg protein following 2 days of 2% (w/v) hypertonic saline administration and to 11.5 +/- 0.9 ng/mg protein with 7 days of treatment. Conversely, posterior pituitary HNMT activity was significantly elevated after hypertonic saline administration. Pituitary stalk transection did not reduce the concentration of histamine in the rat posterior pituitary although HNMT activity was reduced from 18.8 +/- 0.82 munits/gland to 9.22 +/- 1.56 munits/gland (x +/- SEM). These results indicate that histamine released from posterior pituitary mast cells could facilitate AVP release as part of the overall mechanism for osmotic stimulation of AVP secretion and support the concept that most posterior pituitary histamine is not neuronally derived from the brain. HNMT, on the other hand, may be contained in neurons disrupted by stalk section.


Assuntos
Histamina N-Metiltransferase/metabolismo , Liberação de Histamina/efeitos dos fármacos , Metiltransferases/metabolismo , Hipófise/fisiologia , Solução Salina Hipertônica/farmacologia , Cloreto de Sódio/farmacologia , Animais , Arginina Vasopressina/metabolismo , Cinética , Masculino , Hipófise/efeitos dos fármacos , Hipófise/enzimologia , Ratos , Ratos Endogâmicos
12.
Chronobiol Int ; 3(2): 117-22, 1986.
Artigo em Inglês | MEDLINE | ID: mdl-2824068

RESUMO

Circadian rhythms in physiological processes and behaviors were compared with hypothalamic circadian rhythms in norepinephrine (NE) metabolites, adrenergic transmitter receptors, cAMP, cGMP and suprachiasmatic nucleus (SCN) arginine vasopressin (AVP) in a single population of rats under D:D conditions. Eating, drinking and locomotor activity were high during the subjective night (the time when lights were out in L:D) and low during the subjective day (the time when lights were on in L:D). Plasma corticosterone concentration rose at subjective dusk and remained high until subjective dawn. Binding to hypothalamic alpha 1- and beta-adrenergic receptors also peaked during the subjective night. Cyclic cGMP concentration was elevated throughout the 24-hr period except for a trough at dusk, whereas DHPG concentration peaked at dawn. Arginine vasopressin levels in the suprachiasmatic nucleus peaked in the middle of the day. No rhythm was found either in binding to the alpha 2-adrenergic receptor, or in MHPG or cAMP concentration. Behavioral and corticosterone rhythms, therefore, are parallel to rhythms in hypothalamic alpha 1- and beta-receptor binding and NE-release. Cyclic GMP falls only at dusk, suggesting the possibility that cGMP inhibits activity much of the day and that at dusk the inhibition of nocturnal activity is removed. SCN AVP, on the other hand, peaking at 1400 hr, may play a role in the pacemaking function of the SCN that drives these other rhythms.


Assuntos
Comportamento Animal/fisiologia , Ritmo Circadiano , Corticosterona/sangue , Hipotálamo/metabolismo , Animais , Arginina Vasopressina/metabolismo , AMP Cíclico/metabolismo , GMP Cíclico/metabolismo , Norepinefrina/metabolismo , Ratos , Receptores Adrenérgicos/metabolismo , Núcleo Supraquiasmático/metabolismo
13.
Brain Res ; 359(1-2): 368-70, 1985 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-3000525

RESUMO

Chlordiazepoxide pretreatment decreased basal levels of plasma arginine-vasopressin (AVP) and attenuated picrotoxin-induced increases in plasma AVP and blood pressure compared to saline-pretreated spinal animals. Prior administration of RO 15-1788 blocked the effects of chlordiazepoxide on basal plasma AVP as well as picrotoxin-evoked changes in plasma AVP and blood pressure. Thus, interactions at the benzodiazepine receptor may influence basal and evoked changes in plasma AVP concentration.


Assuntos
Arginina Vasopressina/sangue , Clordiazepóxido/farmacologia , Receptores de GABA-A/fisiologia , Animais , Benzodiazepinonas/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Clordiazepóxido/antagonistas & inibidores , Flumazenil , Masculino , Picrotoxina/antagonistas & inibidores , Picrotoxina/farmacologia , Ratos , Ratos Endogâmicos , Receptores de GABA-A/efeitos dos fármacos
14.
Am J Physiol ; 249(3 Pt 1): E317-25, 1985 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-3898868

RESUMO

Patients with uncontrolled insulin-dependent diabetes mellitus have elevations in plasma vasopressin that cannot be accounted for totally by recognized osmotic or nonosmotic stimuli. To investigate the possibility that regulation of vasopressin secretion is abnormal in this disease, we characterized the vasopressin response to osmotic and hemodynamic stimuli in five uncomplicated, well-controlled insulin-dependent diabetics, and compared the results with those found in nondiabetic volunteers. During osmotic stimulation with hypertonic saline, plasma vasopressin increased in close linear correlation with plasma osmolality or sodium in both groups. However, in the diabetics, the lines describing the relationships between plasma sodium and vasopressin were shifted significantly to the left of normal, suggesting resetting of the osmostat. This shift was not due to abnormal stimulation by hyperglycemia, because increasing plasma glucose and osmolality by intravenous infusion of hypertonic dextrose produced no increase in plasma vasopressin in diabetics or normals. Tilt tests produced a slightly exaggerated increase in plasma vasopressin in diabetics, but their basal and upright pulse rate, blood pressure, plasma renin activity, norepinephrine, and hematocrit were all normal. The results indicate that in diabetic patients the osmoreceptor for osmotic regulation of vasopressin secretion is reset in such a way that higher plasma vasopressin levels are observed at comparable levels of plasma sodium. The exact cause and consequence of this abnormality remain to be determined.


Assuntos
Diabetes Mellitus Tipo 1/sangue , Vasopressinas/sangue , Pressão Sanguínea , Diabetes Mellitus Tipo 1/fisiopatologia , Hematócrito , Humanos , Insulina/uso terapêutico , Concentração Osmolar , Valores de Referência , Sódio/sangue , Ureia/sangue
15.
Neuropeptides ; 6(5): 471-83, 1985 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-4058686

RESUMO

Intracerebroventricular (ICV) injections of arginine vasopressin (AVP) in doses of 0.015 nmoles and 0.15 nmoles produced a fall in mean actual pressure heart rate and respiration in pentobarbital anesthetized rats. The changes in mean arterial pressure and respiration after the higher dose were significantly different from saline injection. In contrast, the same doses of AVP given to conscious animals increased both blood pressure and heart rate. Following the 0.15 nmole dose, there was a marked and significant rise in plasma norepinephrine and epinephrine, indicating that activation of the sympathetic nervous system was, at least in part, responsible for the rise in blood pressure. Plasma vasopressin increased by less than 10 pg/ml following injection. Similar doses of a vasopressin pressor antagonist had no significant effect on mean arterial pressure or heart rate. These results indicate that ICV injection of vasopressin has different effects on blood pressure, depending on the presence or absence of anesthesia: depressor responses in the anesthetized animal and pressor responses in the unanesthetized animal.


Assuntos
Hemodinâmica/efeitos dos fármacos , Vasopressinas/farmacologia , Anestesia , Animais , Catecolaminas/sangue , Relação Dose-Resposta a Droga , Injeções Intraventriculares , Masculino , Radioimunoensaio , Ratos , Ratos Endogâmicos , Fatores de Tempo
16.
Am J Physiol ; 249(3 Pt 1): E244-50, 1985 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-2863984

RESUMO

The effect of hemorrhagic shock (40% of blood vol) on the distribution of immunoreactive dynorphin A (Dyn A-IR), [Arg8]vasopressin (AVP-IR), and [Leu5]enkephalin (LE-IR) in the pituitary and brain nuclei was studied in the conscious rat. At 24 h after hemorrhage, the neurointermediate lobe (NIL) showed a reduction in Dyn A-IR (52%) and AVP-IR (32%) and an increase in LE-IR (72%); at this time, the anterior lobe also showed decreased Dyn A-IR (50%) and increased LE-IR (210%). Dyn A-IR, but not LE-IR, was also significantly depleted in some forebrain nuclei in all experimental groups as compared with intact controls, whereas Dyn A-IR in the hypothalamic ventromedial nucleus was elevated only in the sham-control rats. AVP-IR was elevated in the supraoptic nucleus and median eminence (200 and 31%, respectively) 2 and 24 h after bleeding, although plasma AVP returned to normal levels. These data indicate that stress and hypovolemic hypotension produce site and time-dependent change in distribution of dynorphins, AVP, and LE in the central nervous system.


Assuntos
Arginina Vasopressina/análise , Química Encefálica , Dinorfinas/análise , Encefalina Leucina/análise , Hipófise/análise , Choque Hemorrágico/fisiopatologia , Animais , Arginina Vasopressina/sangue , Pressão Sanguínea , Frequência Cardíaca , Hematócrito , Masculino , Radioimunoensaio , Ratos , Ratos Endogâmicos , Distribuição Tecidual
17.
J Pharmacol Exp Ther ; 234(2): 378-85, 1985 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-2991498

RESUMO

Picrotoxin, a gamma-aminobutyric acid (GABA) antagonist, administered to spinal rats elicited dose-related increases in mean blood pressure and circulating plasma vasopressin concentration which were found to be highly correlated (r = 0.952; P less than .001) 6 min after infusion of picrotoxin. Pretreatment with the vasopressin antagonist d(CH2)5Tyr(Me)arginine vasopressin (10 microgram/kg i.v.) blocked the picrotoxin-induced pressor response. Administration of bicuculline (1.0 mg/kg i.v.), a second GABA antagonist, caused an increase in mean blood pressure and plasma vasopressin, whereas strychnine, another central nervous system stimulant thought not to act via a GABAergic mechanism, failed to evoke a significant change in either mean blood pressure or plasma vasopressin. Midcollicular decerebration decreased base-line plasma vasopressin concentrations and also prevented the picrotoxin-induced increase in pressure and vasopressin. The data from this study suggest that blockade of tonic GABAergic inhibition by GABA antagonists causes the release of vasopressin into the systemic circulation which results in a pressor response in spinal rats. The level at which this GABAergic inhibition occurs is not known; however, the GABA antagonists appear to require an intact supraspinal neuraxis to cause the release of vasopressin from the neurohypophysis.


Assuntos
Arginina Vasopressina/metabolismo , Bicuculina/farmacologia , Antagonistas GABAérgicos , Picrotoxina/farmacologia , Medula Espinal/fisiologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Estado de Descerebração , Masculino , Ratos , Ratos Endogâmicos , Receptores Adrenérgicos alfa/efeitos dos fármacos , Receptores de GABA-A/efeitos dos fármacos
18.
J Pharmacol Exp Ther ; 234(2): 463-9, 1985 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-2991502

RESUMO

The effects of agonists at kappa, mu and delta opioid receptors were determined on vasopressin levels in water-deprived rats. Bremazocine and U-50, 488 (kappa agonists) markedly suppressed vasopressin levels, whereas morphine and methadone (mu agonists) and metkephamid (a mixed mu and delta agonist) did not suppress vasopressin levels. Likewise, clonidine, a potent diuretic in normally hydrated rats, did not clearly suppress vasopressin levels. Metkephamid was shown to have a modest diuretic effect in normally hydrated rats but not in water-deprived rats. The diuretic effects of bremazocine were blocked completely by simultaneous treatment with desmopressin, a synthetic vasopressin-like analog. Desmopressin also blocked the diuretic effect of a waterload, but only partially attenuated the diuretic effect of clonidine. These results support the hypothesis that kappa opioid agonists produce a diuretic effect by suppressing plasma levels of vasopressin, and at higher doses produce a pattern of urination similar to animals lacking vasopressin. By comparison, mu and delta opioid agonists have little effect on vasopressin levels in water-deprived rats.


Assuntos
Clonidina/farmacologia , Diurese/efeitos dos fármacos , Endorfinas/farmacologia , Receptores Opioides/efeitos dos fármacos , Vasopressinas/sangue , Animais , Benzomorfanos/farmacologia , Desamino Arginina Vasopressina/farmacologia , Relação Dose-Resposta a Droga , Encefalina Metionina/análogos & derivados , Encefalina Metionina/farmacologia , Masculino , Ratos , Receptores Opioides delta , Receptores Opioides kappa , Receptores Opioides mu
19.
J Pharmacol Exp Ther ; 232(3): 786-94, 1985 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-3973827

RESUMO

The cardiorespiratory, sympathetic and biochemical effects of T-2 toxin were examined in conscious rats and guinea pigs. The pithed rat preparation was also used to evaluate possible direct effects of T-2 on the heart and vasculature. Injection of T-2 (0.5-2.0 mg/kg i.v.) into conscious rats produced prolonged (6-8 hr) hypertension and tachycardia, followed by hypotension. Total peripheral resistance was increased and cardiac output decreased. In guinea pigs, a steady decrease in pressure and rate occurred. Intravenous administration of T-2 to pithed rats did not alter blood pressure or heart rate at a time when, in conscious rats, both blood pressure and heart rate were increased. Significant elevations of arterial plasma norepinephrine, epinephrine and dopamine occurred after T-2, with metabolic acidosis, hypocarbia and hyperoxemia in both conscious rats and guinea pigs. In the rat, increase in plasma vasopressin and prostacyclin were elevated, but thromboxane and leukotriene C4-immunoreactivity were not changed. In pithed rats, T-2 did not increase basal or stimulated plasma catecholamines but produced the same changes in blood gases, pH and lactate. The LD50 values for i.v. T-2 in the rat and guinea pig were 0.74 and 1.30 mg/kg, respectively. The data are consistent with the hypothesis that T-2 toxin disrupts cellular aerobic metabolism, resulting in lactic acidosis, sympathoadrenomedullary activation, variable initial circulatory responses and eventual cardiovascular collapse.


Assuntos
Hemodinâmica/efeitos dos fármacos , Sistemas Neurossecretores/efeitos dos fármacos , Respiração/efeitos dos fármacos , Sesquiterpenos/farmacologia , Sistema Nervoso Simpático/efeitos dos fármacos , Toxina T-2/farmacologia , Animais , Ácidos Araquidônicos/metabolismo , Arginina Vasopressina/sangue , Gasometria , Pressão Sanguínea/efeitos dos fármacos , Débito Cardíaco/efeitos dos fármacos , Catecolaminas/sangue , Cobaias , Frequência Cardíaca/efeitos dos fármacos , Hematócrito , Concentração de Íons de Hidrogênio , Lactatos/sangue , Ácido Láctico , Masculino , Ratos , Ratos Endogâmicos , Medula Espinal/fisiologia , Resistência Vascular/efeitos dos fármacos
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