Activation by Phoneutria nigriventer spider venom of autonomic nerve fibers in the isolated rat heart.

In the isolated rat heart, Phoneutria nigriventer spider venom (10-100 microg) produced a dose-dependent and reversible rise in left ventricular developed pressure. A low dose (10 microg) of venom induced a short-lasting, positive inotropic effect (P < 0.05) with no change in heart rate or coronary flow. At a dose of 50 microg, the venom caused significant positive inotropic and chronotropic responses associated with occasional ventricular arrhythmia, whereas coronary flow was not significantly affected within 10 min after venom administration. The highest dose of venom (100 microg) caused bradycardia, transient cardiac arrest, rhythm disturbances and an increase in end diastolic pressure followed by a reduction in coronary flow. Hearts treated with the non-selective beta-adrenoceptor antagonist propranolol (3 microM) and the selective beta1-adrenoceptor antagonist CGP-20712A (10 microM) were protected against all the cardiac actions of the venom. The selective beta2-adrenoceptor antagonist butoxamine (10 microM) slightly reduced the cardiac response to 50 microg, but not to 100 microg of venom. Butoxamine also prevented the reduction in coronary flow induced by 100 microg of venom. Hearts from reserpine-treated rats (5 mg kg(-1) day(-1), i.p., for 2 days) showed a marked decrease in all venom (< or = 100 microg)-induced cardiac responses. The muscarinic receptor antagonist atropine (1 microM) slightly potentiated the response to 50 microg of venom but had little or no effect on the responses to 100 microg of venom. The cardiac responses to venom (50-100 microg) were unaltered in hearts from rats treated with 8-methyl N-vanillyl-6-nonenamide (capsaicin; 50 mg/kg, s.c.). These findings indicate that P. nigriventer venom releases norepinephrine from cardiac sympathetic nerve endings and this may explain the observed increase in contractile force and heart rate.