Effects of beta-adrenoceptor antagonists on anaphylactic hypotension in conscious rats.

摘要

Anaphylactic shock is sometimes fatal or resistant to therapy in patients treated with propranolol, a nonselective beta-adrenoceptor antagonist, against cardiovascular diseases. However, it remains unknown which subtype of beta-adrenoceptors, beta(1)- or beta(2)-adrenoceptor, is primarily responsible for the detrimental effects of propranolol on anaphylactic hypotension. Effects of beta(1)- and beta(2)-adrenoceptor antagonists were therefore determined on the survival rate and systemic hypotension in conscious Sprague-Dawley rats that suffered from anaphylactic shock. Mean arterial pressure and portal venous pressure were simultaneously measured. The control rats showed a decrease in mean arterial pressure and an increase in portal venous pressure, but did not die within 48h after an injection of ovalbumin antigen. The survival rate of the rats pretreated with propranolol (1mg/kg; n=7), the selective beta(2)-adrenoceptor antagonist ICI 118,551 (0.5mg/kg; n=7), or adrenalectomy (n=7) was significantly smaller than that with the selective beta(1)-adrenoceptor antagonist atenolol (2mg/kg; n=7). However, the changes in mean arterial pressure and portal venous pressure were similar for 10min after antigen among any groups, although propranolol and atenolol attenuated the antigen-induced increase in heart rate. Furthermore, bolus injections of epinephrine (3mug/kg) at 3 and 5min after antigen prevented the death of the atenolol-pretreated rats, but only marginally prolonged the survival rates for the ICI 118,551- or propranolol-pretreated and adrenalectomized rats. In conclusion, in rat anaphylactic shock, inhibition of beta(2)-adrenoceptor causes more detrimental effects than that of the beta(1)-adrenoceptor. These beta-adrenoceptor antagonists may exert detrimental effects on rat systemic anaphylaxis via inhibiting beneficial actions of catecholamines endogenously released from the adrenal gland.