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

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 show 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.