An apparent paradox: attenuation of phenylephrine-mediated calcium mobilization and hyperreactivity to phenylephrine in contralateral carotid after balloon injury.
Balloon catheter injury promotes hyperreactivity to phenylephrine (Phe) in the contralateral carotid. Phe-induced contraction involves calcium mobilization, a process that may be sensitive to reactive oxygen species. In this study, we investigated whether increased reactivity to Phe in the contralateral carotid is due to alterations in calcium mobilization by Phe and reactive oxygen species signaling. Concentration-response curves to Phe were obtained in control and contralateral arteries 4 days after balloon injury. Tiron did not modify Emax to Phe in control arteries but reduced this parameter in the contralateral carotid to control levels. Moreover, immunofluorescence to dihydroethydine showed increased basal oxidative stress in the contralateral artery compared with control artery. Intracellular calcium mobilization by Phe in the contralateral artery was not different from control, but Phe-induced extracellular calcium mobilization was reduced in the contralateral artery compared with that in the control. These data were confirmed by confocal microscopy using Fluo 3-AM. Tiron and SC-236 increased Phe-induced calcium influx in the contralateral artery, which was similar to controls in the same conditions. However, catalase did not modify this response. Taken together, our results suggest that superoxide anions and prostanoids from cyclooxygenase-2 alter pathways downstream of alpha1-adrenoceptor activation in the contralateral carotid in response to injury. This results in reduced Phe-induced calcium influx, despite hyperreactivity to Phe.
Pereira
Aline C
AC
Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil.
Olivon
Vania C
VC
de Oliveira
Ana Maria
AM
D000800:Angioplasty, Balloon / Q000009:adverse effects*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002339:Carotid Arteries / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D020212:Carotid Artery Injuries / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D017382:Reactive Oxygen Species; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D051546:Cyclooxygenase 2; D002118:Calcium