RESUMO
The aqueous extract of Viscum album leaves showed a significant coronary vasodilator activity on the Langendorff's isolated and perfused heart model. The data obtained suggest that the aqueous extract of V. album contains some biologically active principles that may act as inducers of the nitric oxide/soluble guanylate cyclase pathway.
Assuntos
Vasos Coronários/efeitos dos fármacos , Fitoterapia , Extratos Vegetais/farmacologia , Vasodilatadores/farmacologia , Viscum album , Animais , Circulação Coronária/efeitos dos fármacos , Circulação Coronária/fisiologia , Vasos Coronários/fisiologia , Guanilato Ciclase/metabolismo , Cobaias , Coração/efeitos dos fármacos , Coração/fisiologia , Masculino , Óxido Nítrico/metabolismo , Extratos Vegetais/administração & dosagem , Extratos Vegetais/uso terapêutico , Folhas de Planta , Vasodilatadores/administração & dosagem , Vasodilatadores/uso terapêuticoRESUMO
Blood flow regulates vessel tone triggering the release of nitric oxide; however, the mechanism involved in this phenomenon is unknown. We investigated whether coronary flow induces nitric oxide release in the isolated perfused guinea pig heart and the role of the stretch-activated ion channels in the effect of flow. We used gadolinium (3 microM) in order to block these channels, and estimated nitric oxide release by an oxyhemoglobin method. The results have shown a flow-dependent stimulation of nitric oxide release (fivefold increase at perfusion flow of 25 ml/min). Gadolinium inhibited this effect in a dose-dependent fashion. Acetylcholine was able to stimulate nitric oxide release in presence of gadolinium. We concluded that coronary flow stimulates nitric oxide release in the guinea pig heart. Stretch-activated ion channels mediate this effect. Acetylcholine and flow stimulate nitric oxide release by different mechanisms of action.
Assuntos
Circulação Coronária/fisiologia , Canais Iônicos/fisiologia , Mecanorreceptores/fisiologia , Miocárdio/metabolismo , Óxido Nítrico/metabolismo , Acetilcolina/farmacologia , Animais , Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Velocidade do Fluxo Sanguíneo/fisiologia , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Vasos Coronários/fisiologia , Relação Dose-Resposta a Droga , Gadolínio/farmacologia , Cobaias , Técnicas In Vitro , Canais Iônicos/antagonistas & inibidores , Oxiemoglobinas/metabolismo , Resistência Vascular/efeitos dos fármacosRESUMO
UNLABELLED: It has been demonstrated that coronary flow, through hemodynamic forces, stimulates ventricular contraction and atrio-ventricular transmission; however, the mechanisms involved in these effects remain unknown. A possibility to explain the transduction mechanism, from a mechanical stimulus into a physiological response, could be the stretch-activated ion channels. Additionally we explored the role of nitric oxide as mediator of these actions. METHODS: We used the isolated perfused guinea pig heart according to the method of Langendorff, perfused with Krebs solution. We recorded the ventricular contraction by development of left ventricular pressure and the atrio-ventricular transmission. We studied the effects of the stretch activated ion channel blocker; gadolinium. Synthesis of nitric oxide was inhibited by L-NAME and induced with L-arginine. RESULTS: Gadolinium inhibited the stimulating effect of flow on atrio-ventricular transmission and ventricular contraction. Verapamil, a specific blocker of calcium channels, had no effect in the stimulatory effect of flow indicating that this type of calcium channel, do not play significant role in the effects of flow. L-NAME and L-arginine did not have effects on the effects of flow. CONCLUSION: The stimulating effect of coronary flow in these parameters is regulated by stretch-activated ionic channels. This effect is independent of nitric oxide.
Assuntos
Nó Atrioventricular/fisiologia , Circulação Coronária/fisiologia , Contração Miocárdica/fisiologia , Transmissão Sináptica/fisiologia , Animais , Arginina/farmacologia , Pressão Sanguínea/fisiologia , Bloqueadores dos Canais de Cálcio/farmacologia , Inibidores Enzimáticos/farmacologia , Gadolínio/farmacologia , Cobaias , Técnicas In Vitro , Canais Iônicos/antagonistas & inibidores , Canais Iônicos/fisiologia , Masculino , Mecanorreceptores/fisiologia , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase/antagonistas & inibidores , Óxido Nítrico Sintase Tipo III , Transdução de Sinais/fisiologia , Função Ventricular , Verapamil/farmacologiaRESUMO
UNLABELLED: Myocardial perfusion SPECT has a high sensitivity for the diagnosis of myocardial ischemia. Adenosine has been recently used to induce myocardial ischemia in the United States and Europe. At the present time there is not published experience using adenosine in Mexico. METHOD: We studied 22 patients with suspected myocardial ischemia. Coronary angiography was performed in 17 patients. We used a 8 mCi rest Tc-99m sestamibi followed by a 6 minute infusion of adenosine at a dose of 140 ug/kg/min; 24 mCi of Tc-99m were injected after the third minute of adenosine infusion. Patients returned 2 or 3 days later for a new stress study using physical stress or dipiridamole and the images were read using a 20 segments analysis and each segment was scored using a 5 points scale (0 = normal to 4 = absent uptake). The results were then compared with the adenosine images. RESULTS: The segmental score agreement between adenosine and physical or dipyridamole stress were good with 90% exact correlation. The side effects experienced by patients who received dipyridamole and adenosine were similar. CONCLUSION: Adenosine is a good alternative to induce myocardial ischemia. It showed a good correlation with physical or dipyridamole stress test.
Assuntos
Adenosina , Isquemia Miocárdica/diagnóstico por imagem , Tomografia Computadorizada de Emissão de Fóton Único , Adulto , Idoso , Teste de Esforço , Feminino , Humanos , Masculino , México , Pessoa de Meia-IdadeRESUMO
UNLABELLED: The action of adenosine on atrial functional refractory period, as well as on its ability to interrupt atrial flutter is similar to that of digitalis. The latter suggests the possible existence of an adenilic component to digitalis action. To test this possibility, we measured the plasma concentrations of adenosine after ouabain infusion in dogs, and we investigated the effect of digitalis on atrial refractory period and on flutter in conditions of cholinergic inhibition and purinergic blockade. Ouabain was administered until ventricular fibrillation was induced. Blood was obtained from both the coronary sinus and the femoral vein, and adenosine was measured by liquid chromatography. The refractory period was measured by applying an extra stimulus at variable intervals following a train of 10 basic beats. Flutter was induced by stimulation of the posterior internodal pathway. RESULTS: The concentration of adenosine in plasma collected from the coronary sinus increased by more than 100%; the effect of digitalis on atrial refractory period was independent of cholinergic blockade, but it was inhibited by aminophylline; the ability of digitalis to interrupt flutter was modified by aminophylline. CONCLUSION: The antiarrhythmic action of digitalis seems to include an adenilic component, that results from the liberation of adenosine in the heart.
Assuntos
Adenosina/farmacologia , Antiarrítmicos/farmacologia , Glicosídeos Digitálicos/farmacologia , Adenosina/sangue , Animais , Antiarrítmicos/administração & dosagem , Flutter Atrial/sangue , Flutter Atrial/tratamento farmacológico , Flutter Atrial/fisiopatologia , Cães , Avaliação Pré-Clínica de Medicamentos , Interações Medicamentosas , Eletrocardiografia/efeitos dos fármacos , Átrios do Coração/efeitos dos fármacos , Átrios do Coração/fisiopatologia , Masculino , Ouabaína/administração & dosagem , Ouabaína/farmacologia , Ouabaína/intoxicação , Intoxicação/sangue , Intoxicação/fisiopatologia , Receptores Purinérgicos P1/efeitos dos fármacos , Receptores Purinérgicos P1/fisiologiaRESUMO
3-Nitropropionic acid (3-NPA) was identified as the toxic component of several plants and fungi. Recently, it was described that 3-NPA produced hypotension, accompanied by a paradoxical bradycardia. In this study, we identified a possible mechanism of action, explaining the effect of 3-NPA on cardiac tissue. We used isolated, spontaneously beating atria and heart mitochondria to measure electrophysiological properties and mitochondrial oxygen consumption. We also measured Na+/K+ ATPase activity and intracellular ATP levels. In isolated spontaneously beating atria, 3-NPA (10(-4) M) decreased heart rate by 62 +/- 3%. This agent did not affect the amplitude or duration of action potentials. The duration of intervals between two action potentials, however, was prolonged from 530 +/- 285 to 1400 +/- 600 ms after 3-NPA exposure (10(-2) M). Oxygen consumption by heart mitochondria was inhibited by 3-NPA when either malate/glutamate or succinate were used as metabolism substrates. Cytochrome C oxidase activity was not affected by 3-NPA. Finally, atrial ATP content decreased 65 +/- 3% after 3-NPA treatment. In conclusion, we show that 3-NPA decreases atrial rate by increasing the action potential phase 4, probably by inhibition of mitochondrial respiration, thereby decreasing cardiac ATP content. This suggests that 3-NPA-induced bradycardia may be related to intracellular ATP depletion.
Assuntos
Anti-Hipertensivos/toxicidade , Bradicardia/induzido quimicamente , Átrios do Coração/efeitos dos fármacos , Mitocôndrias Cardíacas/efeitos dos fármacos , Propionatos/toxicidade , Trifosfato de Adenosina/metabolismo , Animais , Bradicardia/fisiopatologia , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Eletrofisiologia , Átrios do Coração/enzimologia , Átrios do Coração/fisiopatologia , Frequência Cardíaca/efeitos dos fármacos , Masculino , Mitocôndrias Cardíacas/metabolismo , Nitrocompostos , Técnicas de Cultura de Órgãos , Oxigênio/metabolismo , Consumo de Oxigênio , Ratos , Ratos Wistar , ATPase Trocadora de Sódio-Potássio/metabolismoRESUMO
It has been shown that, changes in the structure of the cardiac glycoside, are related to changes in their biological effects. In the present study we compared the effects of two structurally different digitalis compound (ouabain and ouabagenin), on K+ induced vascular relaxation as an index of the Na+K+ ATPase activity. Ouabain was the most potent compound tested, and had vasoconstrictor effect on the rat aortic rings, as, well as inhibitory effect on the K(+)-induced relaxation. Ouabagenin did not affect either the vascular tone or K(+)-induced relaxation. It is well known that changes in the part of the structure of the cardiac glycoside that contain the sugar, are important to maintain some of their biological effects. In this paper we demonstrate that elimination of the 1-rhamnose in ouabagenin reduces its vascular effects associated to the inhibition of the Na+ K+ ATPase pump.
Assuntos
Aorta/efeitos dos fármacos , Glicosídeos Digitálicos/farmacologia , Contração Miocárdica/efeitos dos fármacos , Potássio/farmacologia , Animais , Aorta/enzimologia , Aorta/fisiologia , Técnicas In Vitro , Masculino , Ouabaína/análogos & derivados , Ouabaína/farmacologia , Ratos , Ratos Sprague-Dawley , ATPase Trocadora de Sódio-Potássio/efeitos dos fármacos , Relação Estrutura-AtividadeAssuntos
Sistema Cardiovascular/efeitos dos fármacos , Cocaína/farmacologia , Cardiomiopatia Dilatada/induzido quimicamente , Vasos Coronários/efeitos dos fármacos , Endocardite/induzido quimicamente , Humanos , Infarto do Miocárdio/induzido quimicamente , Miocardite/induzido quimicamente , Transtornos Relacionados ao Uso de Substâncias/complicações , Vasoconstrição/efeitos dos fármacosAssuntos
Sistema Cardiovascular/efeitos dos fármacos , Cocaína/farmacologia , Animais , Arritmias Cardíacas/induzido quimicamente , Sistema Cardiovascular/metabolismo , Cocaína/farmacocinética , Cocaína/intoxicação , Sistema de Condução Cardíaco/efeitos dos fármacos , Sistema de Condução Cardíaco/fisiologia , Humanos , Fatores de TempoRESUMO
The role of testosterone/17 B estradiol ratios (T/E), on the vasoconstrictor effect of norepinephrine (NE), were studied in strips of carotid arteries from dogs. T/E of 0.1 (T = 1 nM/E = 10 nM) shifted the concentration/effect (C-E) curve of NE to the right. T/E of 10 (T = 10 nM/E = 1 nM) deviated it to the left. T (1 nM and 10 nM) shifted the C-E curve of NE to the right; E = 1 nM did not modify it; E = 10 nM, shifted it to the left. In microsomal fraction of carotid arteries, adrenergic receptors were characterized with 3H-NE binding, and the role of T/E ratios also studied. Under the influence of T/E ratio of 10, the agonist affinity (Ka), was increased from 100 nM-1 to 128 nM-1, the receptors density (Bmax), increased from 78.3 nM to 148 nM. E (1 nM) reduced Ka to 88 nM-1, T did not change any of these parameters. In conclusion, T/E ratios of 10, as in male, may enhance the vasoconstrictor activity of NE, increasing Ka and Bmax of adrenergic receptors.
Assuntos
Estradiol/farmacologia , Norepinefrina/farmacologia , Receptores Adrenérgicos/efeitos dos fármacos , Testosterona/farmacologia , Vasoconstritores/farmacologia , Animais , Artérias Carótidas/efeitos dos fármacos , Artérias Carótidas/metabolismo , Cães , Relação Dose-Resposta a Droga , Interações Medicamentosas , Técnicas In Vitro , Masculino , Norepinefrina/farmacocinética , Receptores Adrenérgicos/metabolismo , Vasoconstrição/efeitos dos fármacos , Vasoconstritores/farmacocinéticaRESUMO
In anesthetized and vagotomized dogs, we investigate the associative effects on blood pressure of norepinephrine (NE) with the three polyamines putrescine (Pt), spermidine (Sd) and spermine (Se). Experimental series were performed under beta adrenergic blockade (propranolol 0.5 mg/Kg, iv.), alpha adrenergic blockade (phenoxybenzamine 15 mg/Kg, iv.), and under calcium antagonistic action (verapamil 0.3 mg/Kg, iv.). The three polyamines induced a potentiation on the hypertensive effect of NE, they change the dose/response curve to the left side in a potency rank of Se greater than Sd greater than Pt. Such potentiation was not different when a beta adrenergic blockade or calcium antagonism was present; however phenoxybenzamine neutralized it. On the other side, polyamines had a hypotensive effect when were administered alone to the animals. Such effect is related to a histamine releasing properties of the polyamines, and was abolished by previous administration of anihistaminic agents chlorpheniramine (5 mg/kg, iv.) and cimetidine (20 mg/Kg, iv.). In conclusion our results indicate that the potentiation of the hypertensive effect of NE by polyamines, could be attained through a mechanism which involves the alpha adrenergic receptors of the vascular smooth muscle but is not related to the calcium channels that show voltage dependence.
Assuntos
Poliaminas Biogênicas/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Norepinefrina/farmacologia , Anestesia , Animais , Clorfeniramina/farmacologia , Cimetidina/farmacologia , Cães , Relação Dose-Resposta a Droga , Feminino , Masculino , Fenoxibenzamina/farmacologia , Propranolol/farmacologia , Putrescina/farmacologia , Espermidina/farmacologia , Espermina/farmacologia , Verapamil/farmacologiaRESUMO
Tetrahydroisoquinolines (TIQs) are alkaloids originated as natural catabolic derivatives of catecholamines (CAT). Dopamine, under special circumstances, condenses with aldehydes to produce tetrahydropapaveroline (THP), salsolinol (SOL) and salsoline (SAL). We investigated the inotropic activity of THP, SOL and SAL on the isometric contractility of papillary muscles isolated from guinea pigs hearts and compared their actions to those corresponding to adrenaline (A) and isopropylarterenol (ISO). In order to analyze their combined effects, TIQs and A were applied simultaneously. THP, SOL and SAL produced positive inotropic effects as beta receptor agonists; their actions were antagonized with propranolol. The inotropic efficacy of TIQs compared to that of catecholamines, is: CAT = 1; SAL = 0.32; THP = 0.47 and SOL = 0.32. Their middle effective dose (DE50), indicates an order of potency of: ISO = SAL greater than A = THP greater than SOL. Combination of THP or ISO with A produces an additive effect; however, SAL behaves as a partial agonist, meaning that it produces an antagonistic, non-competitive type effect on the inotropic action of adrenaline. Chemical structure of TIQs shows significant relationship with their pharmacological activity on ventricular myocardium, similar to that of catecholamines. The influence of the methoxyl group attached to C-7 in SAL, as the only difference with SOL which instead has a hydroxyl group in that position, deserves special mention; such structural difference provides to SAL bigger inotropic efficacy and potency, as well as beta adrenergic antagonistic activity. The results of the present paper emphasize the biological significance of active catabolites from catecholamines as are the tetrahydroisoquinoline compounds.
Assuntos
Dopamina/metabolismo , Epinefrina/farmacologia , Isoproterenol/farmacologia , Isoquinolinas/farmacologia , Contração Miocárdica/efeitos dos fármacos , Papaverina/análogos & derivados , Músculos Papilares/efeitos dos fármacos , Alcaloides de Salsolina/farmacologia , Tetra-Hidropapaverolina/farmacologia , Animais , Cobaias , Técnicas In VitroRESUMO
The effects of increasing doses of intravenous adenosine upon the dissociation haemoglobin curve (DHC) and its relation to the intraerythrocytic level of 2,3-diphosphoglyceric acid (2,3-DPG), were studied in 17 anesthetized dogs. The DHC moved significantly to the left in all dogs except at the dose of 120 micrograms/kg/min which induces a displacement to the right. These changes in the DHC were parallel to the intraerythrocytic levels of 2,3-DPG. We conclude that adenosine modifies the DHC, shifting it generally to the left, and that this effect seems to be related to a change in the intraerythrocytic level of 2,3-DPG.
Assuntos
Adenosina/farmacologia , Ácidos Difosfoglicéricos/sangue , Índices de Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Hemoglobinas/metabolismo , 2,3-Difosfoglicerato , Adenosina/administração & dosagem , Animais , Cães , Eritrócitos/efeitos dos fármacos , Injeções Intravenosas , MasculinoRESUMO
In order to evaluate isopropylarterenol infusion (ISO) as a diagnostic procedure in ischemic heart disease, we performed a clinical study in 54 patients controlled with exercise stress test (ERGO) and validated by coronary arteriography. Eighteen patients had normal coronary arteriographic findings and 36 had coronary artery disease. In both groups the hemodynamic response was similar in either test used (ERGO or ISO), when similar heart rates were reached. The sensitivity of ERGO was 80.55% and 86.11% for ISO and specificity of 77.72% and 72.26% respectively in the diagnosis of coronary artery disease. When both tests are associated their sensitivity is 83.30% and their specificity is 75.0% (Table V). The ISO test was not accompanied with adverse effects and could be considered as a useful method in the diagnosis of coronary heart disease, similar to ERGO. Additionally ISO could be applied to understand some physiopathological mechanisms of ischemic heart disease.
Assuntos
Angiografia Coronária , Doença das Coronárias/diagnóstico , Isoproterenol , Adulto , Idoso , Doença das Coronárias/fisiopatologia , Teste de Esforço , Feminino , Hemodinâmica , Humanos , Infusões Intravenosas , Isoproterenol/administração & dosagem , Masculino , Pessoa de Meia-IdadeRESUMO
In order to study the mechanism of action of AMP on the AV node conduction, 10 patients with re-entrant tachycardia including the AV node in the circuit (SVT) were studied. The mean age was 32.8 +/- 11.1. Tachycardia was induced by programmed atrial stimulation. Electrophysiological studies were made in all the cases. Intravenous injection of AMP suppressed SVT in all the patients in the first part of the study. The mean doses was 0.095 +/- 0.037 mg/Kg., and the mean time was 15.2 +/- 2.6 sec. In the second part (after 0.04 mg/Kg. IV atropine) the induced SVT was suppressed with a mean doses of 0.122 +/- 0.45 mg/Kg of AMP (P = NSD) in a mean time of 16.2 +/- 2.2 sec. (p = NSD). In the last part of this study the intravenous injection of aminophylline (4 mg/Kg) avoided the suppression of induced SV T in 8/10 patients. In to patients the AMP doses was 0.250 mg/Kg., and in the other 0.075 mg/Kg. Our studies demonstrated that the mechanism of action of AMP is by means of agonistic stimulation of purinergic receptors in the AV node.
Assuntos
Monofosfato de Adenosina/farmacologia , Nó Atrioventricular/efeitos dos fármacos , Sistema de Condução Cardíaco/efeitos dos fármacos , Receptores Purinérgicos/efeitos dos fármacos , Taquicardia por Reentrada no Nó Atrioventricular/fisiopatologia , Taquicardia Supraventricular/fisiopatologia , Monofosfato de Adenosina/fisiologia , Adolescente , Adulto , Nó Atrioventricular/fisiopatologia , Feminino , Humanos , Masculino , Receptores Purinérgicos/fisiologiaRESUMO
All natural cardiac glycosides (CG) have a hydroxyl (OH) group attached to carbon 14 (C 14) of the steroid nucleus which has been considered important for their pharmacological action. To investigate the relation between chemical structure and biological activity of CG, we studied the cardiac effects of a semisynthetic derivative if gluco-digitoxigenin that lacks the C 14 hydroxyl group; the compound was named Dig-3 and corresponds to the number of a series of semisynthetic glycosides being studied. On the failing heart of the Starling's heart-lung preparation Dig-3 reverts experimental cardiac failure. Electrophysiological experiments in anesthetized dogs (morphine chloralose) have shown that Dig-3 shortens the functional refractory period of the ordinary atrial myocardium (OAM), and lengthens that of the specialized atrial tissue (SAT). The basal excitability is reduced in both tissues, however OAM is more susceptible to Dig-3 action. The conduction velocity of impulses in SAT diminishes 50% with one tenth of the lethal dose (LD) of Dig-3 whereas in the OAM, an equivalent decrease is achieved with 60% of LD. A-V dissociation induced by the infusion of toxic doses of Dig-3 reverted to sinus rhythm in about 6 min after the administration was stopped. We conclude that the presence of the OH group attached to C 14 of digitalis molecule does not constitute a structural requirement for the preservation of its inotropic and electrophysiological actions on the heart, although its potency is greatly diminished.
Assuntos
Digitoxina/análogos & derivados , Contração Miocárdica/efeitos dos fármacos , Animais , Digitoxina/síntese química , Digitoxina/farmacologia , Digitoxina/toxicidade , Cães , Feminino , Átrios do Coração/efeitos dos fármacos , Insuficiência Cardíaca/tratamento farmacológico , Masculino , Ouabaína/farmacologia , Período Refratário Eletrofisiológico/efeitos dos fármacos , Estimulação Química , Relação Estrutura-Atividade , Fibrilação Ventricular/induzido quimicamenteAssuntos
Antiarrítmicos/farmacologia , Arritmias Cardíacas/fisiopatologia , Sistema de Condução Cardíaco/fisiologia , Modelos Biológicos , Miocárdio/citologia , Animais , Arritmias Cardíacas/tratamento farmacológico , Flutter Atrial/fisiopatologia , Flutter Atrial/cirurgia , Benzimidazóis/farmacologia , Computadores , Cães , Átrios do Coração , Sistema de Condução Cardíaco/efeitos dos fármacos , Humanos , Ouabaína/farmacologia , Quinidina/farmacologiaRESUMO
Quinidine gluconate was administered slowly by intravenous infusion to 20 patients with atrial fibrillation. Nineteen of them had rheumatic heart disease and the other one had Ebstein's disease. The first ten patients received 0.027 mg/kg/min during 6 hs or less if they returned to normal sinus rhythm (SR). The other ten received 0.041 mg/kg/min with the same protocol. Plasma quinidine concentrations were determined in all patients. Atrial functional refractory period was measured in five of the patients returning to normal sinus rhythm. Six patients in the first group were returned to SR. The required time of infusion was 4.2 hs. The maximal quinidine plasma level was 1.91 ug/ml. In the Second group; five patients returned to normal sinus rhythm, four of them in a mean time of 4.75 hs ofinfusion and the other one spontaneously 11 hs after the infusion was finished. The maximal quinidine plasma level in this group was 4.7 ug/ml. Side effects were observed in five patients. Diarrhea in one, vomiting in one, hypotension in two atrial flutter with 1: 1 A-V conduction in one.