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Cardioprotective Action of Ginkgo biloba Extract against Sustained β-Adrenergic Stimulation Occurs via Activation of M2/NO Pathway

2017; Frontiers Media; Volume: 8; Linguagem: Inglês

10.3389/fphar.2017.00220

1663-9812

Thássio Mesquita, Itamar Couto Guedes de Jesus, Jucilene F. dos Santos, Grace Kelly Melo de Almeida, Carla M. L. de Vasconcelos, Sílvia Guatimosim, Fabrício Nunes Macedo, Robervan Vidal dos Santos, José Evaldo Rodrigues de Menezes‐Filho, Rodrigo Miguel‐dos‐Santos, Paulo Tojal Dantas Matos, Sérgio Scalzo, Valter Joviniano Santana‐Filho, Ricardo Luiz Cavalcanti de Albuquerque Júnior, Rose Nely Pereira‐Filho, Sandra Lauton‐Santos,

Neurological Disorders and Treatments

Ginkgo biloba is the most popular phytotherapic agent used worldwide for treatment of several human disorders. However, the mechanisms involved in the protective actions of Ginkgo biloba on cardiovascular diseases remain poorly elucidated. Taking into account recent studies showing beneficial actions of cholinergic signaling in the heart and the cholinergic hypothesis of Ginkgo biloba-mediated neuroprotection, we aimed to investigate whether Ginkgo biloba extract (GBE) promotes cardioprotection via activation of cholinergic signaling in a model of isoproterenol-induced cardiac hypertrophy. Here, we show that GBE treatment (100 mg/kg/day for 8 days, v.o.) reestablished the autonomic imbalance and baroreflex dysfunction caused by chronic β-adrenergic receptor stimulation (β-AR, 4.5 mg/kg/day for 8 days, i.p.). Moreover, GBE prevented the upregulation of muscarinic receptors (M2) and downregulation of β1-AR in isoproterenol treated-hearts. Additionally, we demonstrated that GBE prevents the impaired endothelial nitric oxide synthase activity in the heart. GBE also prevented the pathological cardiac remodeling, electrocardiographic changes and impaired left ventricular contractility that are typical of cardiac hypertrophy. To further investigate the mechanisms involved in GBE cardioprotection in vivo, we performed in vitro studies. By using neonatal cardiomyocyte culture we demonstrated that the antihypertrophic action of GBE was fully abolished by muscarinic receptor antagonist or NOS inhibition. Altogether, our data support the notion that antihypertrophic effect of GBE occurs via activation of M2/NO pathway uncovering a new mechanism involved in the cardioprotective action of Ginkgo biloba.