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 mu g ) produced a dose-dependent and reversible rise in left ventricular develop ed pressure. A low dose (10 mu g) of venom induced a short-lasting, positiv e inotropic effect (P < 0.05) with no change in heart rate or coronary flow . At a dose of 50 mu g, 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 ve nom administration. The highest dose of venom (100 mu g) caused bradycardia , transient cardiac arrest, rhythm disturbances and an increase in end dias tolic pressure followed by a reduction in coronary flow. Hearts treated wit h the non-selective beta-adrenoceptor antagonist propranolol (3 mu M) and t he selective beta(1)-adrenoceptor antagonist CGP-20712A (10 mu M) were prot ected against all the cardiac actions of the venom. The selective beta(2)-a drenoceptor antagonist butoxamine (10 mu M) slightly reduced the cardiac re sponse to 50 mu g, but not to 100 mu g of venom. Butoxamine also prevented the reduction in coronary flow induced by 100 mu g of venom. Hearts from re serpine-treated rats (5 mg kg(-1) day(-1), i.p., for 2 days) showed a marke d decrease in all venom (less than or equal to 100 mu g)-induced cardiac re sponses. The muscarinic receptor antagonist atropine (1 mu M) slightly pote ntiated the response to 50 mu g of venom but had little or no effect on the responses to 100 mu g of venom. The cardiac responses to venom (50-100 mu g) were unaltered in hearts from rats treated with 8-methyl N-vanillyl-6-no nenamide (capsaicin; 50 mg/kg, s.c.). These findings indicate that P. nigri venter venom releases norepinephrine from cardiac sympathetic nerve endings and this may explain the observed increase in contractile force and heart rate. (C) 1998 Elsevier Science B.V. All rights reserved.