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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Chronic Treatment With Acetylcholinesterase Inhibitors Attenuates Vascular Dysfunction in Spontaneously Hypertensive Rats

Texto completo
Autor(es):
Lataro, Renata M. [1] ; Silva, Marcondes A. B. [2] ; Mestriner, Fabiola L. [2] ; Cau, Stefany B. A. [2] ; Tostes, Rita C. A. [2] ; Salgado, Helio C. [3]
Número total de Autores: 6
Afiliação do(s) autor(es):
[1] Univ Fed Santa Catarina, Ctr Biol Sci, Dept Physiol Sci, Florianopolis, SC - Brazil
[2] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Physiol, Ribeirao Preto - Brazil
[3] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, Ribeirao Preto - Brazil
Número total de Afiliações: 3
Tipo de documento: Artigo Científico
Fonte: AMERICAN JOURNAL OF HYPERTENSION; v. 32, n. 6, p. 579-587, JUN 2019.
Citações Web of Science: 1
Resumo

BACKGROUND Acetylcholinesterase inhibition prevents autonomic imbalance, reduces inflammation, and attenuates the development of hypertension. Considering that vascular dysfunction is a crucial feature of arterial hypertension, we investigated the effects of chronic administration of acetylcholinesterase inhibitors-pyridostigmine or donepezil-on vascular reactivity of spontaneously hypertensive rats (SHR). METHODS Endothelium-dependent relaxant responses to acetylcholine (ACh) and contractile responses induced by electric field stimulation (EFS) and alpha-adrenergic agonist were studied in mesenteric resistance arteries from SHR and Wistar Kyoto rats. SHR were treated for 16 weeks with vehicle, pyridostigmine (1.5 mg/kg/day) or donepezil (1.4 mg/kg/day). RESULTS Pyridostigmine and donepezil decreased the vasoconstrictor responses to EFS, which were increased in vehicle-treated SHR. Acetylcholinesterase inhibition increased the modulatory effects of nitric oxide (NO) on SHR vascular reactivity, that is, N(omega)-nitro-(L)-arginine methyl ester (L-NAME) increased EFS-induced contractions and reduced ACh-induced relaxation, with more significant effects in pyridostigmine-and donepezil-treated SHR. The acetylcholinesterase inhibitors also decreased vascular reactive oxygen species levels. CONCLUSIONS This study demonstrates for the first time that long-term administration of acetylcholinesterase inhibitors, pyridostigmine or donepezil, attenuates vascular reactivity dysfunction in SHR by decreasing reactive oxygen species generation and increasing NO bioavailability; possibly via increased endothelial NO synthase activity, and inhibition of NADPH oxidase activity. (AU)

Processo FAPESP: 12/03349-1 - Efeitos dos bloqueios, central e periférico, da acetilcolinesterase na função cardiocirculatória e na inflamação observada em ratos espontaneamente hipertensos
Beneficiário:Helio Cesar Salgado
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 11/12460-0 - Efeitos dos bloqueios, central e periférico, da acetilcolinesterase na função cardiocirculatória e na inflamação observada em ratos espontaneamente hipertensos (SHR)
Beneficiário:Renata Maria Lataro
Linha de fomento: Bolsas no Brasil - Pós-Doutorado