O carvacrol reduz a pressão arterial via ativação de canais receptores de potencial transiente em ratos espontaneamente hipertensos

• Ano de defesa: 2014
• Autor(a) principal: Dantas, Bruna Priscilla Vasconcelos
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal da Paraíba; Brasil; Farmacologia; Programa de Pós-Graduação em Produtos Naturais e Sintéticos Bioativos; UFPB
• Palavras-chave em Português: Carvacrol; L-type voltage-operated Ca2+ channels; Aorta; Canais de Ca2+ operados por voltagem tipo-L; Canais potencial receptor transiente; Vasorelaxamento; Ratos espontaneamente hipertensos - SHR; Transient receptor potential channel; Vasorelaxation; CIENCIAS BIOLOGICAS::FARMACOLOGIA
• Link de acesso: https://repositorio.ufpb.br/jspui/handle/tede/8055

TRP channels have been extensively studied in many physiological and pathological processes involved in blood pressure regulation. Carvacrol is well known to act on TRP channels in the vasculature, however there are no studies of its effects in hypertensive rats. Our aim was to evaluate the contribution of TRP channels in hypertension and evaluate the effects of carvacrol on TRP channels of SHR. In an electrophysiological approach, carvacrol (300 μM) inhibited the barium current, suggesting a reduction of calcium influx through L-type voltage-operated Ca2+ channels. We found that the mRNA expression of the following TRP channels: TRPV1 (p=0.0007), TRPV4 (p=0.0002), TRPM7 (p=0.0091) and TRPM8 (p=0.0008) are decreased and TRPC1 (p=0,02) are increased in SHR compared to control. In aortic rings preparations precontracted with 1 μM of phenylephrine, carvacrol (10-8 - 3x10-4 M) induced vasorelaxation in WKY (pD2 = 4.88  0.09, Emax = 100.73  2.24%, n = 6) and SHR (pD2 = 4.93  0.08, Emax= 110.06  2.07%, n = 6) in the presence of functional endothelium and that effect was not altered after endothelium removal in WKY (pD2 = 5.09  0.08, Emax = 99.60  0.88%, n = 6) and SHR (pD2 = 5.00  0.08, Emax = 101.23  1.96%, n = 6), proposing an endotheliumindependent mechanism. To assess the role of TRP channels, aortic rings were incubated with ruthenium red. In this assay, the vasorelaxant response was not changed in the WKY. On the other hand both potency (p<0.001) and efficacy (p<0.001) were reduced in SHR, suggesting that carvacrol could activate the subtypes TRPV in hypertensive animals. When using magnesium, equally potency (p<0.001) and pharmacological efficacy (p<0.01) were attenuated in both WKY and SHR, suggesting the involvement of TRPM7. In preparations with 2-APB, CPZ and BCTC, the vasorelaxant effect was potentiated (p<0.01) in both WKY and SHR, suggesting the participation of TRPV1, TRPM8 and TRPM7 channels in the vasorelaxant effect induced by carvacrol. Nevertheless, in the presence of capsaicin, the vasodilator effect was attenuated (p<0.001) in both WKY and SHR endorsing a possible action of carvacrol on TRPV1 and TRPV4 channel. In addition, in vivo studies showed that carvacrol produced hypotension and bradycardia in unanesthetized WKY and SHR. In order to address the cardiovascular responses in vivo, we performed experiments using ruthenium red and capsaicin to evaluate the contribution of TRP channels in this effect. Our results suggested an action of carvacrol on TRPV1 and TRPV4, confirming the in vitro assays. In conclusion, these results suggest that the expression of TRPV1, TRPV4, TRPM7 and TRPM8 was reduced and TRPC1 increased in SHR and carvacrol induced a vasorelaxant effect probably by acting on TRPV1, TRPV4, TRPC1, TRPM7 and TRPM8 in SHR. Furthermore, the in vivo effects induced by carvacrol exhibited a hypotensive and bradycardic activity and this effect, at least in part, is due to an activation of TRPV1 and TRPV4 channels in these responses.