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.
de Araújo Júnior
João Xavier
JX
Instituto de Química e Biotecnologia, Universidade Federal de Alagoas, Cidade Universitária, Tabuleiro dos Martins, Maceió, Alagoas, Brazil. joaoxjr@yahoo.com.br
Julien
Claude
C
Barrès
Christian
C
de Medeiros
Isac Almeida
IA
Ribeiro
Eurica Adélia Nogueira
EA
Lima
Lídia Moreira
LM
Barreiro
Eliezer Jesus
EJ
D000818:Animals; D001049:Apnea / Q000139:chemically induced* / Q000503:physiopathology; D001285:Atropine / Q000494:pharmacology; D052117:Benzodioxoles / Q000009:adverse effects / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D001919:Bradycardia / Q000139:chemically induced* / Q000503:physiopathology; D002211:Capsaicin / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects*; D007022:Hypotension / Q000139:chemically induced* / Q000503:physiopathology; D007211:Indoles / Q000494:pharmacology; D007275:Injections, Intravenous; D008297:Male; D009025:Morpholines / Q000009:adverse effects / Q000494:pharmacology*; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex / Q000187:drug effects; D016713:Ritanserin / Q000494:pharmacology; D000077526:Tropisetron; D014628:Vagotomy
D052117:Benzodioxoles; D007211:Indoles; D009025:Morpholines; C555808:N-(4'-dihydro)piperoylthiomorpholine; D016713:Ritanserin; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D011732:Pyridoxal Phosphate; D000077526:Tropisetron; D001285:Atropine; D002211:Capsaicin