Lataro, Renata M.
Silva, Marcondes A. B.
Mestriner, Fabiola L.
Cau, Stefany B. A.
Tostes, Rita C. A.
Salgado, Helio C.
Total Authors: 6
 Univ Fed Santa Catarina, Ctr Biol Sci, Dept Physiol Sci, Florianopolis, SC - Brazil
 Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Physiol, Ribeirao Preto - Brazil
 Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, Ribeirao Preto - Brazil
Total Affiliations: 3
AMERICAN JOURNAL OF HYPERTENSION;
Web of Science Citations:
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)