Alterações cardiovasculares induzidas pelo veneno da aranha (Phoneutria nigriventer) em ratos anestesiados




The changes induced in the mean arterial blood pressure (MABP) of anaesthetised rats following the administration of armed spider (Phoneutria nigriventer) venom have been investigated. The intravenous injection of Phoneutria nigriventer venom (PNV; 0.1 mg/kg) evoked a brief and reversible decrease in the MABP whereas a higher dose of venom (0.3 mg/kg) caused a biphasic response characterized by a short lasting hypotension followed by a sustained and prolonged hypertension (40-50 min). These changes were accompanied by tachycardia, salivation, fasciculations, defecation and respiratory disturbances. Pretreatment of the animais with atropine (10 mg/kg), propranolol (100 mg/kg), phenoxybenzamine (100 mg/kg) and indomethacin (4 mg/kg) did not significantly affect the MABP changes induced by PNV. Similarly, the bradykinin B2 receptor antagonist Hoe 140 (0.6 mg/kg), the PAF antagonist WEB 2086 (20 mg/kg), the NK1 receptor antagonist SR 140333 (0.5 mg/kg) and the nitric oxide synthase inhibitor Nro-nitro-L-arginine methyl ester (10 mg/kg) had no significant effect on the PNV-induced MABP changes. The increase in the MABP induced by PNV was also not significantly affected by either angiotensin 11 receptor antagonist losartan (10 mg/kg) or the endothelin ET A receptor antagonist FR 139317 (30 mg/kg). The A TP-dependent potassium channel antagonist glibenclamide (50 mg/kg) reduced by 40% the hypotension induced by Pf JV without affecting the hypertensive response. Pretreatment of the animais with Ltype Ca2+ channel antagonists such as verapamil (10-100 μ/kg/min), diltiazem (40-120 /-l9/kg/min) and nifedipine (0.3-10 mg/kg) markedly attenuated the PNVinduced hypertension. Verapamil (30 μ/kg/min) and diltiazem (120μ/kg/min) also promptly reversed the established hypertension induced by PNV when infused 8 min after venom injection. Our results indicate that the brief decrease of blood pressure induced by PNV is partially due to A TP-dependent or calcium activated channels activation. The prolonged hypertension seems to result from direct calcium entry in vascular and/or cardiac muscles. Phoneutria nigriventer venom (PNV; 50 and 100 μg) was also investigated in isolated rat hearts by the Langendorff method. Doses of 50 μg evoked a significant positive inotropism (increase of left ventricule developed pressure; LVDP) associated with discreete positive cronotropism. Higher doses of PNV (100 ~g) caused an immediate increase of L VDP followed by bradicardy and temporary atrium-ventricule blockad (AVB). This was accompained by significant reduction of coronary blood flow. These changes were prevented by the P-blocker propranolol indicating that such effects are caused by activation of sympathetic nerve endings and hence noradrenaline release. Since atropine potentiated the increase of L VDP and attenuated the bradicardia induced by PNV, it is likely that PNV also induces the release of acetylcholine from parassympathetic nerve endings. However, the release of both noradrenaline and acetylcholine from the rat hearts does not probably account for the cardiovascular changes observed in vivo. The in vivo effect is likely to be of peripheral or CNS, rather than cardiac, origin.


calcio - antagonistas aranha - veneno hipertensão

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