Acetylcholinesterase Inhibition Attenuates the Development of Hypertension and Inflammation in Spontaneously Hypertensive Rats

Autor(es)

Lataro, Renata M. ^[1] ; Silva, Carlos A. A. ^[1] ; Tefe-Silva, Cristiane ^[2] ; Prado, Cibele M. ^[2] ; Salgado, Helio C. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dept Physiol, Med Sch Ribeirao Preto, BR-14049 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Dept Pathol, Med Sch Ribeirao Preto, BR-14049 Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: AMERICAN JOURNAL OF HYPERTENSION; v. 28, n. 10, p. 1201-1208, OCT 2015.
• Citações Web of Science: 15

Resumo

BACKGROUND It is hypothesized that chronic increase of availability of acetylcholine, resulting from the effect of antiacetylcholinesterases, may prevent autonomic imbalance and reduce inflammation yielding benefic effects for cardiovascular disorders in hypertension. The effect of long-term administration of antiacetylcholinesterase agents with central and/or peripheral action, i.e., donepezil and pyridostigmine, were investigated on arterial pressure (AP), sympathovagal balance, plasma cytokine levels, and cardiac remodeling in spontaneously hypertensive rats (SHR). METHODS Chronic treatment with donepezil or pyridostigmine started before the onset of hypertension. AP was measured by plethysmography every 4 weeks. At the end of 16 weeks of treatment, methylatropine was used to evaluate the cardiac vagal tone; AP and pulse interval (PI) variability were also evaluated followed by plasma and heart collection for analysis. RESULTS Pyridostigmine, which does not cross the blood-brain barrier, increased cardiac vagal tone, and reduced cardiomyocyte diameter and collagen density, but did not affect the AP and plasma cytokine levels. Donepezil, which crosses the blood-brain barrier, attenuated the development of hypertension, increased cardiac vagal tone, and improved AP and PI variability. Likewise, donepezil reduced the plasma levels of tumor necrosis factor-alpha, interleukin 6, and interferon gamma, besides reducing cardiomyocyte diameter and collagen density. CONCLUSIONS Donepezil attenuated the development of hypertension in SHR probably involving antiinflammatory effects, indicating that acetylcholinesterase inhibition yields benefic effects for antihypertensive therapy. (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
• Modalidade de apoio: 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
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado