Asunto(s)
Atropina/sangre , Cromatografía Líquida de Alta Presión/métodos , Compuestos Organofosforados/sangre , Compuestos de Pralidoxima/sangre , Espectrometría de Masas en Tándem/métodos , Animales , Humanos , Límite de Detección , Modelos Lineales , Masculino , Ratas , Ratas Wistar , Reproducibilidad de los ResultadosRESUMEN
Although it is well-established that severe poisoning by organophosphorus (OP) compounds strongly affects the cardiorespiratory system, the effects of sub-lethal exposure to these compounds on the neural control of cardiovascular function are poorly explored. The aim of this study was to evaluate the effects of acute sub-lethal exposure to chlorpyrifos (CPF), a commonly used OP insecticide, on three basic reflex mechanisms involved in blood pressure regulation, the peripheral chemoreflex, the baroreflex and the Bezold-Jarisch reflex. Adult male Wistar rats were injected intraperitoneally with a single dose of CPF (30â¯mg/kg) or saline (0.9%). 24â¯h after injections, cardiovascular reflexes were tested in awake rats. Potassium cyanide (KCN) and phenylbiguanide (PBG) were injected intravenously to activate the chemoreflex and the Bezold-Jarisch reflex, respectively. The baroreflex was activated by phenylephrine and sodium nitroprusside infusions. Blood samples were taken for measurements of butyrylcholinesterase (BChE) activity while acetylcholinesterase (AChE) activity was measured in brainstem samples. Animals treated with CPF presented signs of intoxication such as ataxia, tremor, lacrimation, salivation, tetany, urination and defecation. The hypertensive and the bradycardic responses of the chemoreflex as well as the hypotensive and bradycardic responses of the Bezold-Jarisch reflex were attenuated in CPF treated animals (Pâ¯<â¯0.05). Concerning the baroreflex responses, CPF treatment reduced the bradycardia plateau, the range and the gain of the reflex (Pâ¯<â¯0.05). Plasma BChE and brainstem AChE were both reduced significantly after CPF treatment (Pâ¯<â¯0.05). Our results showed that acute sub-lethal exposure to CPF impairs the cardiovascular responses of homeostatic and defensive cardiovascular reflexes. These effects are associated with a marked inhibition of plasma BChE and brainstem AChE.
Asunto(s)
Barorreflejo/efectos de los fármacos , Tronco Encefálico/efectos de los fármacos , Cloropirifos/toxicidad , Acetilcolinesterasa/sangre , Acetilcolinesterasa/metabolismo , Animales , Tronco Encefálico/enzimología , Butirilcolinesterasa/sangre , Butirilcolinesterasa/metabolismo , Inhibidores de la Colinesterasa/toxicidad , Proteínas Ligadas a GPI/sangre , Proteínas Ligadas a GPI/metabolismo , Insecticidas/toxicidad , Masculino , Proyectos Piloto , Ratas , Ratas Wistar , Pruebas de Toxicidad AgudaRESUMEN
Anatomical studies have demonstrated the existence of purinergic P2 receptors in the nucleus ambiguus (NA), a site containing cardiac vagal motoneurons. However, very little is known about the functional role of these receptors in central cardiac vagal regulation. The aims of our study were to evaluate the following: (1) the blood pressure and heart rate responses following purinoceptor activation within the NA; (2) the role of purinoceptors and excitatory amino acid (EAA) receptors in mediating the cardiovascular responses evoked by ATP and L-glutamate stimulation of NA; and (3) the role of NA purinoceptors in mediating the cardiovascular responses of the Bezold-Jarisch reflex. In anaesthetized rats, microinjection of L-glutamate (5.0 nmol/50 nl) into the NA induced a marked and immediate onset bradycardia with minimal change in arterial pressure. Microinjection of ATP into the NA induced a dose-dependent (0.31-6.0 nmol/50 nl) bradycardia and pressor responses. It is noteworthy that the bradycardia occurred either before or simultaneously with a pressor response (when present), indicating that it was not a baroreceptor reflex mediated response due to the rise in arterial pressure. The pressor response was prevented by α(1)-adrenergic blockade with prazosin, whereas muscarinic blockade with methyl-atropine abolished the evoked bradycardia. Ipsilateral microinjection of PPADS (a P2 receptor antagonist; 500 pmol/100 nl) into the NA significantly attenuated the ATP-induced bradycardia but spared the pressor response. In contrast, PPADS in the NA had no effect on the L-glutamate-evoked bradycardic response. Ipsilateral injection of kynurenic acid (a non-selective EAA receptor antagonist; 10 nmol/50 nl) into the NA totally blocked the bradycardia induced by l-glutamate and partly attenuated the ATP induced bradycardia. Finally, both the depressor and the bradycardic responses of the Bezold-Jarisch reflex were attenuated significantly (P < 0.01 and P < 0.05, respectively) following bilateral microinjection of PPADS into the NA. These results identify ATP and purinergic P2 receptors within the ventrolateral medulla as excitatory to cardiovagal neurons. Additionally, our data show that P2 receptors within the ventrolateral medulla are integral to the cardiovascular responses of the Bezold-Jarisch reflex.
Asunto(s)
Sistema Cardiovascular/inervación , Bulbo Raquídeo/fisiología , Receptores Purinérgicos P2/fisiología , Adenosina Trifosfato/farmacología , Antagonistas de Receptores Adrenérgicos alfa 1/farmacología , Animales , Derivados de Atropina/farmacología , Barorreflejo/efectos de los fármacos , Barorreflejo/fisiología , Presión Sanguínea/efectos de los fármacos , Sistema Cardiovascular/efectos de los fármacos , Sistema Cardiovascular/metabolismo , Antagonistas de Aminoácidos Excitadores/farmacología , Ácido Glutámico/farmacología , Frecuencia Cardíaca/efectos de los fármacos , Ácido Quinurénico/farmacología , Masculino , Bulbo Raquídeo/metabolismo , Antagonistas Muscarínicos/farmacología , Prazosina/farmacología , Antagonistas del Receptor Purinérgico P2/farmacología , Fosfato de Piridoxal/análogos & derivados , Fosfato de Piridoxal/farmacología , Ratas , Ratas Wistar , Receptores de Glutamato/metabolismo , Receptores Purinérgicos P2/metabolismo , Nervio Vago/efectos de los fármacos , Nervio Vago/fisiologíaRESUMEN
The aim of the present study was to investigate the cardiovascular activity of Scorpaena plumieri venom in both in vivo and in vitro models. In anesthetized rats, doses of the venom (14-216 microg protein/kg) induced a transient increase in the mean arterial pressure. However at higher dose (338 microg protein/kg) this effect was followed by a sudden hypotension and the animal evolved to death. The heart rate was temporarily increased and followed by bradycardia using doses > or =108 microg/kg. In isolated rat hearts the crude venom (5-80 microg protein) produced dose-dependent positive ventricular chronotropic, inotropic, lusitropic and coronary vasoconstriction responses. Partial purification of an active fraction (CF, cardiovascular fraction) which reproduced the cardiovascular effects induced by crude venom on isolated hearts was achieved by conventional gel filtration chromatography. Adrenergic blockades, prazosin and propranolol, significantly attenuated these responses. The coronary vasoconstriction response to CF was also attenuated by chemical endothelium denudation. In conclusion, the data showed that S. plumieri fish venom induces disorders in the cardiovascular system. It also suggests that alpha(1) and beta-adrenergic receptors, and the vascular endothelium, are involved at least partially, in these cardiac effects.