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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
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]
Total Authors: 6
Affiliation:
[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
Total Affiliations: 3
Document type: Journal article
Source: AMERICAN JOURNAL OF HYPERTENSION; v. 32, n. 6, p. 579-587, JUN 2019.
Web of Science Citations: 1
Abstract

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)

FAPESP's process: 12/03349-1 - Effects of acetylcholinesterase blockade, central and peripheral, in the cardiocirculatory function and inflammation observed in spontaneously hypertensive rats
Grantee:Helio Cesar Salgado
Support type: Regular Research Grants
FAPESP's process: 11/12460-0 - Effects of acetylcholinesterase blockade, central and peripheral, in the cardiocirculatory function and inflammation observed in spontaneously hypertensive rats
Grantee:Renata Maria Lataro
Support type: Scholarships in Brazil - Post-Doctorate