Cardiovascular effects of a novel synthetic analogue of naturally occurring piperamides.

Cardiovascular responses to intravenous administration of a piperamide analogue, LASSBio 365, were investigated in anesthetized rats. LASSBio 365 [62.5-1000 microg/kg, intravenously (IV)] has potent cardiovascular effects that include hypotension and bradycardia, accompanied by a brief pressor effect and apnea. Bilateral vagotomy or atropine injection (2 mg/kg, IV) completely abolished the bradycardia. A drop in blood pressure was abolished in bivagotomized rats. However, it was only inhibited in atropine-treated rats. The apnea was inhibited by both treatments. The Bezold-Jarisch reflex (ie, hypotension, bradycardia, and apnea) induced by LASSBio 365 is altered neither by 5-HT3 antagonist (tropisetron, 0.1 mg/kg, intraarterially) nor by the P2x antagonist (PPADS, 8.6 mg/kg, IV). The pressor component was affected neither by any of these interventions nor by the 5-HT2 antagonist (ritanserin, 0.5 mg/kg, i.a.). In capsaicin-pretreated rats (50 mg/kg, subcutaneously), all responses evoked by LASSBio 365 were abolished, including the pressor effect, which was inhibited. The data show that LASSBio 365 evokes the Bezold-Jarish reflex, neither via serotonergic receptors nor purinergic receptors but perhaps via the vanilloid pathway.