Antihypertensive activity of secoisolariciresinol diglucoside (SDG) isolated from flaxseed: Role of guanylate cyclase

Abstract

Secoisolariciresinol diglucoside (SDG), a lignan isolated from flaxseed, is a phytoestrogen. Estrogens and phytoestrogen from soy have been reported to have mild hypotensive effects. Effects of SDG on arterial pressures are not known. The objective of this study was to determine whether (a) SDG has a hypotensive effect, and (b) the hypotensive effect is mediated through the L-arginine-nitric oxide pathway. The studies were conducted in anesthetized Sprague Dawley normotensive rats weighing between 450 and 500 grams Carotid arterial pressures were recorded to investigate the changes in the arterial pressures and heart rate with various doses of SDG. Maximum drops in the mean arterial pressure, which occurred at 15 minutes after intravenous SDG, were 40%, 41%, and 47%, respectively, with 10 mg, 15 mg, and 20 mg/kg of SDG. The pressures tended to recover, but even at the end of four hours, the percent drops in the mean arterial pressures were 33, 22, and 29, respectively, with 10 mg, 15 mg, and 20 mg/kg of SDG. The drops in the diastolic and mean arterial pressures were slightly higher than systolic pressures. Smaller doses of SDG (3 and 5 mg/kg) produced dose-dependent decreases in the systolic, diastolic, and mean arterial pressures. Heart rate remained unchanged. Pretreatment with N^G-monomethyl-L-arginine (L-NMMA), an inhibitor of nitric oxide synthase, did not prevent the SDG-induced reduction in arterial pressures. However, pretreatment with methylene blue (MB), a nonspecific, and oxadiazolo quinoxalin (ODQ), a specific inhibitor of guanylate cyclase, completely prevented the SDG-induced reduction in the arterial pressures. These results suggest that SDG is a long-acting hypotensive agent, and that the hypotensive effect is mediated through the guanylate cyclase enzyme.