Levobupivacaine induces vasodilatation, but not vasoconstriction, in rat mesenteric artery / Levobupivacaína induz vasodilatação, mas não vasoconstrição em artéria mesentérica de rato

Introduction: Levobupivacaine (LEVO) can replace analgesia because it exhibits low toxicity and causes minor vasoconstriction, enabling its use in patients in whom vasoconstrictors are contraindicated. Objective: We aimed to evaluate the effects of LEVO in isolated rat superior mesenteric artery by using the vascular reactivity technique and compare its effect to that of lidocaine. Material and method: Arterial rings were obtained from the mesenteric artery of male Wistar rats and kept in organ baths. For recording isometric contractions, each ring was suspended by cotton threads from a force transducer, which was connected to a data acquisition system. Result: Both lidocaine and LEVO did not show a vasoconstrictor effect on the basal tone of the arterial rings with functional endothelium. However, when the rings were pre-contracted with phenylephrine, both drugs were able to induce concentration-dependent vasodilatation. The vasodilator effect induced by LEVO did not change after removal of the endothelium, or with the addition of tetraethylammonium (1 mM), a non-selective K+ channel blocker. In the rings without functional endothelium, which were pre-contracted with depolarizing Tyrode's solution (KCl 80 mM), LEVO-induced vasodilatation was not significantly different from that observed in the rings pre-contracted with phenylephrine. Moreover, it did not show a significant additional vasodilator effect compared to the maximal vasodilator effect of nifedipine. Conclusion: This study demonstrated that LEVO produces a vasodilator effect in the rat superior mesenteric artery in an endothelium-independent manner. This effect seems to be mediated via Ca2+ channel blockade in the vascular smooth muscle cells.

Introdução: Levobupivacaína pode ser uma nova alternativa para analgesia por apresentar baixa toxicidade e vasoconstrição, permitindo sua utilização em pacientes que apresentam contra-indicação no uso de vasoconstritores. Objetivo: Avaliar os efeitos da levobupivacaína utilizando a técnica de reatividade vascular em artéria mesentérica isolada de rato e comparar este efeito à lidocaína. Material e método: Anéis foram obtidos da artéria mesentérica de ratos machos Wistar e foram mantidos em cubas. Para o registro das contrações isométricas, cada anel foi suspenso por linhas de algodão fixadas a um transdutor de força acoplado a um sistema de aquisição. Resultado: Tanto a lidocaína como a levobupivacaína não apresentaram efeito vasocontritor sobre o tônus basal em anéis com endotélio functional. No entanto, quando os anéis foram pré-contraídos com fenilefrina, ambas as drogas induziram um vasorrelaxamento concentração-dependente. O efeito vasorrelaxante causado pela levobupivacaína não foi diferente após a remoção do endotélio, ou com o tetraetilamônio (1mM), um bloqueador não seletivo dos canais para. K+. Em anéis sem endotélio funcional e pré-contraídos com solução despolarizante de Tyrode (KCl 80mM), o vasorelaxamento induzido pela levobupivacaína não foi significativamente diferente daquele observado em anéis pré-contraídos com fenilefrina e não apresentou um efeito adicional significativo sobre o relaxamento máximo da nifedipina. Conclusão: Este estudo demonstrou que a levobupivacaína produz efeito vasorrelaxante em artéria mesentérica de rato, que é endotélio independente. Este efeito parece envolver os bloqueadores de canais para Ca2+ em célula muscular vascular lisa.

Cardiovascular effects induced by Cymbopogon winterianus essential oil in rats: involvement of calcium channels and vagal pathway.

OBJECTIVES: This study has investigated the cardiovascular effects of the Cymbopogon winterianus essential oil (EOCW) in rats. C. winterianus is a plant used in folk medicine for the treatment of hypertension. METHODS: For the measurement of haemodynamic and ECG parameters, male Wistar rats under anaesthesia were cannulated in the abdominal aorta and lower vena cava and electrodes were subcutaneously implanted in their paws. For an in-vitro approach, the rats were killed and the superior mesenteric artery was removed and cut into rings (1-2 mm). These rings were then mounted in organ baths containing Tyrode's solution at 37 degrees C and gassed with carbogen. KEY FINDINGS: In rats, EOCW (1-20 mg/kg, i.v.) induced dose-dependent hypotension and tachycardia. These effects were not affected by L-NAME or indometacin, but were partially reduced after atropine administration. EOCW (20 mg/kg only) also induced bradycardia-associated sinoatrial blockade, junctional rhythm, and first-degree atrioventricular block, which was abolished after atropine administration or vagotomy. In arterial rings, EOCW (0.1-3000 microg/ml) induced relaxation of phenylephrine tonus that was not affected by removal of the endothelium. These relaxations were similar to those observed in rings without endothelium precontracted with KCl 80 mm. EOCW was able to antagonize the CaCl(2) (30-300 mum) induced contractions in depolarizing solution (KCl 60 mm). CONCLUSIONS: These results demonstrated that EOCW induced hypotension and vasorelaxation. These effects appeared to be mainly mediated by Ca(+2)-channel blocking. Furthermore, the higher dose of EOCW induced transient bradycardia and arrhythmias due to a cardiac muscarinic activation secondary to a vagal discharge.