RESUMO
The effects of 7,8-(methylenedioxi)-14-alpha-hydroxyalloberbane HCl (CH-38083), a structurally new, selective and potent alpha 2-adrenoceptor antagonist, and of idazoxan, were studied on both the spontaneous activity of the postganglionic sympathetic renal nerve and on the clonidine- or xylazine-induced inhibitory action in anaesthetized cats. The drug CH-38083 (30-200 micrograms/kg, i.v.) caused a sustained increase of the sympathetic activity and blood pressure. Larger doses of idazoxan (200-500 micrograms/kg, i.v.) were needed to induce similar effects. Both antagonists were effective in antagonizing the sympatho-inhibitory effect of clonidine or xylazine. The excitatory response to selective alpha 2-adrenoceptor antagonists suggests that the sympathetic output undergoes tonic inhibition due to a permanent alpha 2-adrenoceptor stimulation.
Assuntos
Antagonistas Adrenérgicos alfa/farmacologia , Alcaloides de Berberina/farmacologia , Berberina/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Rim/inervação , Receptores Adrenérgicos alfa/efeitos dos fármacos , Sistema Nervoso Simpático/fisiologia , Animais , Berberina/análogos & derivados , Gatos , Clonidina/farmacologia , Iodeto de Dimetilfenilpiperazina/farmacologia , Dioxanos/farmacologia , Feminino , Idazoxano , Masculino , Sistema Nervoso Simpático/efeitos dos fármacos , Xilazina/farmacologiaRESUMO
As shown by structure-activity relationship studies in 8-(substituted-amino)-4-aryl-2-methyl-1,2,3,4-tetrahydroisoquinolines, the most important structural requirement for a marked antidepressant action is the presence of an ureido, (alkoxycarbonyl)amino, or [(alkylamino)acyl]amino group attached to the isoquinoline skeleton in position 8. In one of the biological tests a significant difference was found between 8-amino-4-phenyl-2-methyl-1,2,3,4-tetrahydroisoquinoline (nomifensine) and the new compounds synthesized. Nearly all compounds substituted in the amino group either decrease the spontaneous motility in mice or exert no effect on it. Two syntheses have been elaborated for the preparation of the compounds represented by the general formulas II-V where R1 = hydrogen, halogen, or methyl; Y = CONHR, OCOR, or CO(CH2)nNHR, in which R = alkyl or aralkyl or NHR = cyclic amine and n = 1-2. The syntheses start either from the corresponding 8-amino-4-aryl-2-methyl-1,2,3,4-tetrahydroisoquinolines or from the corresponding noncyclized amino alcohols. Of the compounds, 4-(p-chlorophenyl)-8-[(ethoxy-carbonyl)amino]-2-methyl-1,2,3,4- tetrahydroisoquinoline was found to possess the highest activity.
Assuntos
Antidepressivos/síntese química , Dopamina/metabolismo , Isoquinolinas/síntese química , Animais , Pressão Sanguínea/efeitos dos fármacos , Gatos , Antagonistas de Dopamina , Indicadores e Reagentes , Isoquinolinas/farmacologia , Masculino , Camundongos , Atividade Motora/efeitos dos fármacos , Ratos , Ratos Endogâmicos , Comportamento Estereotipado/efeitos dos fármacos , Relação Estrutura-AtividadeRESUMO
Transmitters and cotransmitters of the sympathetic nervous system are involved in the regulation of a variety of immune cell functions. However, it is not entirely clear what stimuli lead to the release of these molecules in immune organs. In this study, we investigated whether local ischemia can cause the parallel release of norepinephrine and its cotransmitter, ATP, in the spleen. Ischemic-like conditions, simulated by transient (15 min) O(2) and glucose deprivation, elicited a reversible increase in the release of both norepinephrine and purines from superfused spleen strips preloaded with [3H]norepinephrine or [3H]adenosine. HPLC analysis of the released tritium label revealed a net increase in the amount of ATP, ADP, AMP, adenosine, inosine, hypoxanthine and xanthine in response to ischemic-like condition. Selective O(2) or glucose deprivation, and Ca(2+)-free conditions differentially affected the outflow of [3H]norepinephrine and [3H]purines, indicating that they derived from different sources. The ABC transporter inhibitors glibenclamide (100 microM) and verapamil (100 microM) as well as low-temperature inhibited [3H]purine release evoked by ischemic-like conditions. Surgical denervation of the spleen reduced endogenous catecholamine content and [3H]norepinephrine uptake of the spleen, but not that of [3H]adenosine. In summary, these results demonstrate the release of norepinephrine and purines in response to an ischemic-like condition in an immune organ. Although both could provide an important source of extracellular catecholamines and purines involved at various levels of immunomodulation, the source and mechanism of norepinephrine and purine efflux seem different.
Assuntos
Adenosina/farmacocinética , Isquemia/imunologia , Isquemia/metabolismo , Norepinefrina/farmacocinética , Baço/metabolismo , Simpatomiméticos/farmacocinética , Vasodilatadores/farmacocinética , Adenina/farmacocinética , Difosfato de Adenosina/farmacocinética , Monofosfato de Adenosina/farmacocinética , Trifosfato de Adenosina/farmacocinética , Animais , Cálcio/farmacologia , Hipoxantina/farmacocinética , Inosina/farmacocinética , Masculino , Ratos , Ratos Wistar , Baço/irrigação sanguínea , Baço/inervação , Simpatectomia , Sistema Nervoso Simpático/efeitos dos fármacos , Sistema Nervoso Simpático/imunologia , Sistema Nervoso Simpático/metabolismo , Tetrodotoxina/farmacologia , Trítio , Xantina/farmacocinéticaRESUMO
Dyskinesia is frequently seen in neurological disorders affecting the basal ganglia. Iminodipropionitrile (IDPN) produces a somewhat similar motor syndrome in rodents, one that is a possible model for dyskinesia. Because in previous studies the compound (N-[2-hydroxy-3-(1-piperidinyl) propoxy]-3 pyridine-carboximidoyl-chloride) (Bimoclomol, BRLP-42) was shown to provide protection against IDPN-induced retinopathy; we investigated the effect of BRLP-42 on IDPN-induced motor changes and on IDPN-induced cerebral amino acid level changes in rats and mice. IDPN had a biphasic effect on motor activity in C57BL/6 mice: it was a depressant for 24 days and a stimulant after 30 days. Bimoclomol inhibited the motor depressant effect and enhanced the stimulatory effect of IDPN in this mouse strain. In BALB/cBy mice and Sprague Dawley rats IDPN produced persistent vertical head movements and changes in the level of glutamic acid in brain. Bimoclomol reduced the effect of IDPN on head movements and blocked the effect on cerebral glutamate; by itself it had no effect on motor activity in either species. Bimoclomol inhibited ischemia-induced [3H]norepinephrine release from rat hippocampal slices. Our findings indicate that Bimoclomol could have a beneficial effect on some dyskinesias, and on drug-induced vertical head movements.
Assuntos
Imidas/farmacologia , Atividade Motora/efeitos dos fármacos , Nitrilas/farmacologia , Piridinas/farmacologia , Animais , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Técnicas In Vitro , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Norepinefrina/farmacologia , Ratos , Ratos Sprague-DawleyRESUMO
Release of [3H]dopamine ([3H]DA) from rat striatal slices kept under hypoxic or/and glucose-free conditions was measured using a microvolume perfusion method. The corresponding changes in nucleotide content were determined by reverse-phase high-performance liquid chromatography (RPHPLC). The resting release of [3H]DA was not affected by hypoxia, but under glucose-free conditions massive [Ca2+]o-independent release of [3H]DA was observed. Hypoxia reduced the energy charge (E.C.) and the total purine content from 19.36 +/- 4.15 to 6.98 +/- 1.83 nmol/mg protein. Glucose deprivation by itself, or in combination with hypoxia, markedly reduced the levels of adenosine 5'-triphosphate (ATP), adenosine diphosphate (ADP) and adenosine monophosphate (AMP). The E.C under glucose-free conditions was significantly reduced from 0.73 +/- 0.04 to 0.44 +/- 0.20. When the tissue was exposed to hypoxic and glucose-free conditions for 18 min the level of ATP was reduced to 3.15 +/- 0.11 nmol/mg protein. However, when the exposure time was 30 min the ATP level was further reduced to 1.11 +/- 0.37 nmol/mg protein. The resting release was enhanced in a [Ca2+]o-independent manner, but there was no release in response to stimulation, and tetrodotoxin did not affect the enhanced resting release, indicating that the release was not associated with axonal activity. Similarly, 50 microM ouabain, inhibitor of Na+/K(+)-activated ATPase, enhanced the release of [3H]DA at rest in a [Ca2+]o-independent manner. It seems very likely that the reduced ATP level under glucose-free conditions leads to an inhibition of the activity of Na+/K(+)-ATPase that results in reversal of the uptake processes and in [Ca2+]o-independent [3H]DA release from the axon terminals.
Assuntos
Nucleotídeos de Adenina/metabolismo , Isquemia Encefálica/metabolismo , Corpo Estriado/metabolismo , Dopamina/metabolismo , Glucose/deficiência , Hipóxia Encefálica/metabolismo , Animais , Corpo Estriado/irrigação sanguínea , Modelos Animais de Doenças , Metabolismo Energético/fisiologia , Técnicas In Vitro , Masculino , Ratos , Ratos Wistar , TrítioRESUMO
Phenytoin (DPH), in a low dose (2 mg/kg) was found to potentiate reflex elevations in blood pressure and responses of the nictitating membrane induced either by the electrical stimulation of the sciatic nerve or by intravenously applied pentetrazol in light anaesthetized cats. Pressor responses to carotid occlusion under chloralose anaesthesia were also potentiated. In contrast a high dose (20 mg/kg) of DPH exerted an inhibitory effect on these responses. These effects of DPH on sympathetic reflex responses proved to be long-lasting. Intravenously applied picrotoxin (0.05 mg/kg) or the same dose of ouabain, injected into the vertebral artery, partially reversed the inhibitory effect of DPH (20 mg/kg). Our data support the suggestion that DPH exerts its inhibitory action by effecting ionic fluxes in the CNS, mostly in inhibitory structures.
Assuntos
Fenitoína/farmacologia , Reflexo/efeitos dos fármacos , Sistema Nervoso Simpático/efeitos dos fármacos , Animais , Pressão Sanguínea/efeitos dos fármacos , Gatos , Iodeto de Dimetilfenilpiperazina/farmacologia , Potenciais Evocados/efeitos dos fármacos , Feminino , Técnicas In Vitro , Masculino , Membrana Nictitante/efeitos dos fármacos , Ouabaína/farmacologia , Pentilenotetrazol/farmacologia , Picrotoxina/farmacologia , Escopolamina/farmacologiaRESUMO
The effects of alpha 2-adrenoceptor ligands on electrically stimulated [3H]acetylcholine release from longitudinal muscle strips of guinea-pig ileum were examined. Xylazine or oxymetazoline reduced the release of [3H]acetylcholine in a concentration-dependent manner, both these actions being antagonized by idazoxan, CH 38083, or WB 4101. Prazosin, considered as an alpha 2B-adrenoceptor antagonist, failed to modify the inhibitory effects of xylazine or oxymetazoline. It is concluded that the alpha 2-adrenoceptors involved in the modulation of acetylcholine release from cholinergic axon terminals of guinea-pig ileum are of the alpha 2A subtype.
Assuntos
Acetilcolina/metabolismo , Íleo/inervação , Plexo Mientérico/metabolismo , Receptores Adrenérgicos alfa/fisiologia , Animais , Axônios/metabolismo , Axônios/ultraestrutura , Colina/fisiologia , Estimulação Elétrica , Feminino , Cobaias , Técnicas In Vitro , Cinética , Masculino , Músculo Liso/inervação , Plexo Mientérico/ultraestrutura , Terminações Nervosas/metabolismo , Oximetazolina/farmacologia , Receptores Adrenérgicos alfa/classificação , Trítio , Xilazina/farmacologiaRESUMO
The role of alpha 1- and alpha 2-adrenoceptors in the vascular effects of catecholamines, either released locally from sympathetic nerve endings (e.g., in vascular smooth muscle) or derived from the adrenal medulla or administered intravenously, was studied using selective antagonists of these adrenoceptors. The ganglionic stimulant dimethylphenyl-piperazinium-iodide (DMPP) exerted dual actions on blood pressure: a rapid and short-term pressor reaction (phase I) resulting from catecholamine release elicited by ganglion stimulation, followed by a more sustained blood pressure elevation (phase II) resulting from the circulating catecholamines released from the adrenal medulla. The selective alpha 2-adrenoceptor, but a not subtype selective, antagonist 7,8-(methylenedioxi)-14-alpha-alloberbane HCl (CH-38083) (50-100 micrograms/kg, IV) significantly (p < 0.05) inhibited the pressor effects of epinephrine and norepinephrine given intravenously and phase II of the DMPP-induced pressor reaction. Idazoxan exerted similar effects, but at higher doses (400-600 micrograms/kg, IV). WB-4101 (50-100 micrograms/kg, IV) and BRL-44408 (2-3 mg/kg, IV), two selective alpha 2A-adrenoceptor antagonists, had the same activity as CH-38083, except did not inhibit the pressor effect of intravenously administered norepinephrine. The alpha 2B-adrenoceptor selective antagonist, ARC-239 (150 micrograms/kg, IV) did not influence phase II of DMPP-induced pressor reaction. Prazosin (200 micrograms/kg, IV), an antagonist of alpha 1 and alpha 2B-adrenoceptors, reduced blood pressure, the pressor response to intravenously administered epinephrine, and phase I of the DMPP-induced pressor effect. In addition, it completely inhibited the pressor responses to DMPP remaining after administration of CH-38083. These results suggest that the postsynaptically located alpha 1- and alpha 2(A and B)-adrenoceptors are involved in pressor response to norepinephrine and epinephrine, and are sensitive and accessible to catecholamines released locally from the axon terminals, and from the circulation to a different extent. These results may have great therapeutical importance in hypertension, for which the involvement of both a high level of circulating and locally released catecholamines may be indicative of the usefullness of a combination (alpha 1- and alpha 2-adrenoceptors- and Ca-channel-blocking agents) therapy.
Assuntos
Antagonistas Adrenérgicos alfa/farmacologia , Pressão Sanguínea/fisiologia , Norepinefrina/metabolismo , Receptores Adrenérgicos alfa 1/metabolismo , Receptores Adrenérgicos alfa 2/metabolismo , Sistema Nervoso Simpático/metabolismo , Animais , Berberina/análogos & derivados , Berberina/farmacologia , Gatos , Iodeto de Dimetilfenilpiperazina/farmacologia , Dioxanos/farmacologia , Feminino , Estimulantes Ganglionares/farmacologia , Imidazóis/farmacologia , Indóis/farmacologia , Isoindóis , Masculino , Prazosina/farmacologiaRESUMO
The apomorphine-antagonistic effects of EGYT-2509, a novel neuroleptic compound, has been studied by two different methods suitable for investigating the dopaminergic modulation of sympathetic output. (1) In cats lightly anaesthetized with urethane (600 mg kg-1 i.p.), blood pressure (BP) reflexes evoked by electrical stimulation of the sciatic nerve were inhibited by apomorphine (0.2 mg kg-1 i.v.) at low frequencies of stimuli (2-8 Hz), while the BP reflexes were facilitated by apomorphine at higher frequencies of stimulation; the evoked contractions of the nictitating membrane were depressed in the entire range of frequencies applied. EGYT-2509 (1.5 mg kg-1 i.v.) antagonized both the inhibition and facilitation of pressor reflexes induced by apomorphine. EGYT-2509, given alone, in doses exceeding 1.5 mg kg-1 either did not influence or inhibited the responses of nictitating membrane and of BP; the inhibition could be antagonized by haloperidol. The apomorphine-induced sustained hypotension was inhibited by EGYT-2509 (18.5 mg kg-1): after EGYT-2509, higher doses of apomorphine (0.7 vs 0.2 mg kg-1) were required for the effect. Sustained hypotension could be elicited by EGYT-2509, too; after apomorphine, smaller doses of EGYT-2509 (8.5 vs 18.5 mg kg-1) were enough to decrease BP. (2) In cats anaesthetized with chloralose and urethane (50 and 400 mg kg-1 i.p., respectively), apomorphine (0.2 mg kg-1) inhibited the spontaneous activity of the postganglionic renal sympathetic nerve.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Antipsicóticos/farmacologia , Apomorfina/farmacologia , Dibenzoxazepinas/farmacologia , Reflexo/efeitos dos fármacos , Sistema Nervoso Simpático/efeitos dos fármacos , Animais , Sistema Nervoso Autônomo/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Gatos , Clorpromazina/farmacologia , Feminino , Haloperidol/farmacologia , Técnicas In Vitro , Rim/efeitos dos fármacos , Rim/inervação , Masculino , Membrana Nictitante/efeitos dos fármacosRESUMO
One hundred adult patients, undergoing elective open heart surgery over a period of 4 months, were studied to assess the practice of ventilation in the post operative period. The anaesthetic technique employed used moderate doses of morphine, supplemented with halothane and a muscle relaxant. The decision to extubate was based on clinical assessment, and satisfactory blood gases following a 45 minute T-piece trial. The patients were ventilated for an average duration of 8 hours and 2 minutes and 59 out of 100 patients were extubated within 8 hours. Patients undergoing coronary artery bypass graft were ventilated for significantly longer durations (10 hours 28 minutes) (p < 0.05) and had significantly lower arterial oxygen tension (p < 0.01) 30 minutes after extubation, as compared with those undergoing valvular surgery. Also patients whose bypass time exceeded 2 hours had significantly longer extubation times (p < 0.05) as compared with those who had a bypass time less than 1 hour. T piece trial was found to be a satisfactory method of weaning in all the patients.
Assuntos
Ponte de Artéria Coronária , Doença das Coronárias/cirurgia , Doenças das Valvas Cardíacas/cirurgia , Próteses Valvulares Cardíacas , Ventilação com Pressão Positiva Intermitente , Cuidados Pós-Operatórios , Adulto , Valva Aórtica/cirurgia , Feminino , Hemodinâmica/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Valva Mitral/cirurgiaAssuntos
Sistema Nervoso Autônomo/fisiologia , Pressão Sanguínea/efeitos dos fármacos , Fibras Colinérgicas/fisiologia , Reflexo , Animais , Sistema Nervoso Autônomo/efeitos dos fármacos , Gatos , Feminino , Masculino , Membrana Nictitante/efeitos dos fármacos , Membrana Nictitante/inervação , Membrana Nictitante/fisiologia , Oxotremorina/farmacologia , Fisostigmina/farmacologia , Nervo Isquiático/efeitos dos fármacosAssuntos
Anticonvulsivantes/síntese química , Isoquinolinas/síntese química , Animais , Anticonvulsivantes/toxicidade , Eletrochoque , Isoquinolinas/farmacologia , Isoquinolinas/toxicidade , Dose Letal Mediana , Camundongos , Pentilenotetrazol/antagonistas & inibidores , Convulsões/prevenção & controle , Relação Estrutura-AtividadeAssuntos
Acetilcolina/antagonistas & inibidores , Epinefrina/farmacologia , Pirimidinonas/farmacologia , Ducto Deferente/efeitos dos fármacos , Animais , Sinergismo Farmacológico , Cobaias , Técnicas In Vitro , Masculino , Contração Muscular/efeitos dos fármacos , Ácidos Nicotínicos/farmacologia , Fisostigmina/farmacologia , Pilocarpina/farmacologiaRESUMO
Responses to i.v. administration of dopamine, apomorphine, piribedil and bromocriptine were investigated in the feline mesenteric vascular bed. Dopamine increases the mesenterial flow in doses of 0.3 to 30 micrograms/kg; its effect can be inhibited by 1 to 3 mg/kg of sulpiride. Apomorphine and piribedil also increased the blood flow, but only in 20 to 200 times higher doses; they show a tachyphylaxis phenomenon and their maximal activity is 32 and 59 per cent, respectively, that of dopamine. Apomorphine is a partial agonist of dopamine and can inhibit the activity of the transmitter amine. Bromocriptine has no activity on the feline mesenterial flow. The postsynaptic dopamine receptors of the cat can be characterized by the following: strong efficacy of dopamine and lower ones of apomorphine, piribedil and of sulpiride. The presynaptic dopamine receptors are involved mostly in the hypotension, they are activated by low doses of apomorphine, and piribedil and by higher doses of dopamine; sulpiride reacts with these receptors in much lower doses than with the postsynaptic ones.
Assuntos
Apomorfina/farmacologia , Dopamina/farmacologia , Piperazinas/farmacologia , Piribedil/farmacologia , Circulação Esplâncnica/efeitos dos fármacos , Animais , Pressão Sanguínea/efeitos dos fármacos , Bromocriptina/farmacologia , Artérias Carótidas/efeitos dos fármacos , Gatos , Dopamina/fisiologia , Interações Medicamentosas , Fêmur/irrigação sanguínea , Nomifensina/farmacologia , Fenoxibenzamina/farmacologia , Fluxo Sanguíneo Regional/efeitos dos fármacos , Circulação Renal/efeitos dos fármacos , Sulpirida/farmacologia , Vasodilatação/efeitos dos fármacosRESUMO
The influence of dopaminergic agonists on the spontaneous and evoked activity of the sympathetic postganglionic renal efferent fibres was studied in lightly anaesthetized cats (urethane, 600 mg/kg, ip). Apomorphine, bromocriptine and piribedil (0.2, 0.07 and 0.4 mg/kg iv, respectively) depressed the spontaneous activity of the renal nerve. Electrical stimulation (16 V, 0.3 ms, 2-128 Hz, 2 s) of the sciatic nerve elicited a burst of activity of the sympathetic efferents followed by a silent period. Apomorphine and piribedil (the same doses as above) prolonged the duration of the silent periods. All these effects of dopaminergic agonists were antagonized by haloperidol (0.05-0.1 mg/kg iv). The results suggest that administration of dopaminergic agonists leads to preponderance of inhibition in the somato-sympathetic reflex integration.
Assuntos
Dopamina/fisiologia , Sistema Nervoso Simpático/fisiologia , Animais , Apomorfina/farmacologia , Bromocriptina/farmacologia , Gatos , Vias Eferentes/efeitos dos fármacos , Vias Eferentes/fisiologia , Estimulação Elétrica , Eletrofisiologia , Potenciais Evocados/efeitos dos fármacos , Feminino , Haloperidol/farmacologia , Rim/inervação , Masculino , Piribedil/farmacologia , Sistema Nervoso Simpático/efeitos dos fármacosRESUMO
Apomorphine inhibited the nictitating membrane contractions elicited by pre- or postganglionic stimulation of the cervical sympathetic nerve but did not influence even in higher doses the effect of noradrenaline and adrenaline on this organ. The inhibition evoked by apomorphine could be antagonized by haloperidol but was not influenced by phentolamine and propranolol. Dopamine and noradrenaline inhibited the nictitating membrane contractions elicited by nerve stimulation, but clonidine was ineffective in our experiments. Haloperidol antagonized the inhibition evoked by dopamine but did not influence the similar effect of noradrenaline.
Assuntos
Apomorfina/farmacologia , Membrana Nictitante/efeitos dos fármacos , Sistema Nervoso Simpático/efeitos dos fármacos , Transmissão Sináptica/efeitos dos fármacos , Animais , Apomorfina/antagonistas & inibidores , Gatos , Clonidina/farmacologia , Dopamina/farmacologia , Haloperidol/farmacologia , Contração Muscular/efeitos dos fármacos , Inibição Neural , Membrana Nictitante/fisiologia , Norepinefrina/farmacologia , Fentolamina/farmacologia , Receptores Adrenérgicos/efeitos dos fármacosRESUMO
The experiments were carried out in cats anaesthetized with chloralose and urethane. The preganglionic sympathetic nerve was stimulated and blood flow in the common carotid artery and the contractions of the nictitating membrane were recorded. Three intravenously given dopaminomimetics inhibited the vasoconstriction and nictitating membrane contractions induced by nerve stimulation. The rank order of the drugs was: bromocriptine greater than apomorphine greater than piribedil. The relative potencies on carotid blood flow were 100:30:3.1, respectively. The presynaptic site of activity was discussed.
Assuntos
Artérias Carótidas/inervação , Receptores Dopaminérgicos/efeitos dos fármacos , Vasoconstrição/efeitos dos fármacos , Animais , Apomorfina/farmacologia , Bromocriptina/farmacologia , Gatos , Dopamina/farmacologia , Estimulação Elétrica , Membrana Nictitante/efeitos dos fármacos , Sistema Nervoso Simpático/fisiologiaRESUMO
In cats lightly anesthetized with urethane (600 mg/kg, i.p.) reflexes of the blood pressure (BP) and of the nictitating membrane (NM) were elicited by stimulation of the sciatic nerve (16 V, 0.3 ms, 1-128 Hz, 2 s or 2 min) prior to and after the administration of apomorphine (0.05-0.2 mg/kg, i.v.) or piribedil (0.4-1.0 mg/kg, i.v.). In case of short-train (2 s) stimulation, both dopaminergic agonists shifted the frequency-response curves of NM contractions to the right, i.e. depressed NM reflexes in the entire range of the stimulation frequencies applied. At the same time, BP reflexes were depressed only in the range of lower frequencies (1-4 Hz). At higher rates (32-128 Hz) BP reflexes were potentiated. The reactions of BP to sustained (2 min) stimulations displayed a flat pressor plateau in response to lower-frequency stimulation, and a two-component pattern (an initial pressor peak followed by a plateau) to the higher-frequency one. Compatibility with the effects seen to short-train stimulations, the dopaminergic agonists prolonged the rise-time and augmented the amplitude of the initial pressor peak to sustained stimulations with lower and higher frequencies, respectively. The plateau of the pressor response to higher frequencies was depressed by higher doses (greater than 0.4 mg/kg) of piribedil. Administration of haloperidol (0.05-0.2 mg/kg, i.v.) resulted only in a partial restoration of the reflexes of BP and NM. The manifold effects of dopaminergic agonists on the somato-autonomic reflexes studied support the thought than NM and BP reflexes are organized, at least partially, in different ways.