Protective effects of calcitonin gene-related peptide on guinea-pig cardiac anaphylaxis

Anaphylactic events occurring in cardiac tissues can result in cardiac dysf unction via vasoconstriction and arrhythmias. Calcitonin gene-related pepti de (CGRP) is the most potent vasodilator and possesses anti-arrhythmic acti on. We examined the influence of CGRP on cardiac anaphylaxis in guinea-pigs . In the Langendorff-per fused heart of passively sensitized guinea-pigs, a ntigen challenge evoked a decrease in coronary flow, left ventricular press ure and its maximum first derivatives (+/-dP/dt(max)) and an increased hear t rate. Antigen challenge also induced atrioventricular conduction block. T reatment with CGRP (1 or 3 nM) significantly improved the recovery of cardi ac function and reduced the incidence and duration of atrioventricular bloc k without influencing the increased heart rate. Pretreatment with capsaicin caused effects similar to those of CGRP and markedly elevated the content of CGRP in coronary effluent. Ischaemic preconditioning, induced by two cyc les each of 5 min global ischaemia and 5 min reperfusion, also improved car diac function and raised the level of CGRP in coronary effluent. The protec tive effects of ischaemic preconditioning were abolished in the presence of the CGRP receptor antagonist CGRP(8-37). Histamine release did not differ significantly during any of the interventions. The findings of the present study indicate that, in guinea-pig hearts, CGRP protects against cardiac an aphylaxis and that the cardioprotection by CGRP is independent of histamine release.