Acute And Late Repercussions Of Topiramate Exposure During Adolescence In Female Wistar Rats: Effects On The Vascular Endothelium Function And Blood Pressure

Acute And Late Repercussions Of Topiramate Exposure During Adolescence In Female Wistar Rats: Effects On The Vascular Endothelium Function And Blood Pressure

• Autor
• Deborah Gomes da Silva
• Co-autores
• Kawane Fabricio Moura , Amanda Cristina de Souza , Camila Borecki Vidigal , Kenny Gutemberg Nunes Silva , Maria do Carmo Pinho Franco , Graziela Scalianti Ceravolo
• Resumo

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  Introduction: Topiramate (TOP) is approved for the treatment of epilepsy and migraine prophylaxis in adolescents. Recently, it has been reported that treatment with TOP can increase cardiovascular risk factors. However, at least in females, the effect of TOP treatment on vascular endothelium and blood pressure has not been investigated. Aim: To evaluate the vascular endothelium function and blood pressure of adolescent and adult female rats exposed to TOP during adolescence. Methods: Female Wistar rats were exposed to TOP (41mg/kg/day) or vehicle (CTR group) by gavage from postnatal day (PND) 28 to 50. TOP and CTR groups were evaluated in estrus phase at PND51 or PND90. The thoracic aorta reactivity to phenylephrine (Phenyl), acetylcholine (ACh) and sodium nitroprusside (SNP) was evaluated in the presence (E+) or absence of endothelium (E-). Groups were compared by the maximum response (maxR) and pD2 (data not shown). Mean blood pressure (MBP) was determined by indirect method. Data were expressed as mean±SEM or median (1st-3rd quartile) and analyzed by two-way ANOVA, test t or Mann-Whitney U (*p<0.050, n=8-12/group) (CEUA/UEL:100/2018). Results: The maxR(g) to Phenyl was similar between the groups at PND51 [E+: CTR:1,61±0,08 vs TOP:1,62±0,08; E-: CTR: 2,63±0,07 vs TOP:2,59±0,12] and PND90 [E+: CTR:1,51±0,09 vs TOP:1,34±0,07; E-: CTR:3,16±0,07 vs TOP:3,28±0,08]. The maxR(% relaxation) to ACh and SNP at PND51 [(ACh) CTR:93,47±1,25 vs TOP:92,45±1,16; (SNP) CTR:96,24±0,76 vs TOP:97,76±0,63 ] and at PND90 [(ACh) CTR:92,59±1,10 vs TOP:90,20±1,19; (SNP) CTR:95,04±0,86 vs TOP:95,61±1,05] were similar between the groups. Also, for the MBP (mmHg) there was no difference between CTR and TOP [PND51: CTR:98,3±1,1 vs TOP:97,9±1,7; PND90: CTR:96,0(91,5-100,5) vs TOP:98,0(97,0-99,0]. Conclusion: These results demonstrate that TOP exposure during adolescence does not alter, in the short and long term, the aortic reactivity and MBP of female Wistar rats, suggesting that TOP in the dose and period used is safe concerning this parameter.

• Palavras-chave
• Vascular reactivity, Cardiovascular, Adolescents
• Modalidade
• Comunicação oral
• Área Temática
• Disfunção endotelial