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Minerva Cardioangiologica 2020 Jul 10

DOI: 10.23736/S0026-4725.20.05243-3


lingua: Inglese

Nitric oxide/cGMP signaling pathway and potassium channels contribute to hypotensive effects of nothofagin

Claudio H. da SILVA 1, Rhanany A. PALOZI 2, Priscila de SOUZA 3, Camila L. de ALMEIDA 3, Valdir CECHINEL-FILHO 3, Emerson L. LOURENÇO 1, Arquimedes GASPAROTTO JUNIOR 2

1 Laboratory of Preclinical Research of Natural Products, Paranaense University, Umuarama, Brazil; 2 Laboratory of Electrophysiology and Cardiovascular Pharmacology, Faculty of Health Sciences, Universidade Federal da Grande Dourados, Dourados, Brasil; 3 Graduate Program in Pharmaceutical Sciences, Nucleus of Chemical-Pharmaceutical Investigations (NIQFAR), University of Vale do Itajaí, Itajaí, Brazil


BACKGROUND: Nothofagin is a mono-C-glycoside of 4,2’,4’,6’-tetrahydroxy- dihydrochalcone that is commonly found in Aspalathus linearis, Nothofagus fusca, and Leandra dasytricha. A wide range of biological effects has been attributed to nothofagin, including antioxidant, diuretic, renoprotective, antiplatelet, and antithrombotic effects. Although nothofagin is pharmacologically active, its effects on blood pressure remain unknown. In the present study, we investigated whether nothofagin causes acute and prolonged hypotension in male Wistar rats, and we investigated the molecular mechanisms that underlie these hemodynamic effects.
METHODS: Hypotensive effects of nothofagin (0.3, 1, and 3 mg/kg) were evaluated after acute intraduodenal administration and after 7 days of oral treatment. Using pharmacological antagonists and inhibitors, we explored the involvement of the prostaglandin/cyclic adenosine monophosphate and nitric oxide/cyclic guanosine monophosphate pathways and K+ channels in nothofagin-induced hypotension.
RESULTS: Acute and prolonged nothofagin administration significantly decreased systolic blood pressure and mean arterial pressure in Wistar rats. Pretreatment with N(G)-nitro-L- arginine methyl ester, methylene blue, and tetraethylammonium prevented the hypotensive effect of nothofagin.
CONCLUSIONS: These results shows that nothofagin induces a hypotensive response in Wistar rats, and this effect depends on K+ channel opening in smooth muscle cells through nitric oxide signaling.

KEY WORDS: Hypertension; Hypotensive; Nitric oxide, Nothofagin; Potassium channel

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