title: Miso (Japanese soybean paste) soup attenuates salt-induced sympathoexcitation and left ventricular dysfunction in mice with chronic pressure overload.
abstract: The hypothalamic mineralocorticoid receptor (MR)-angiotensin II type 1 receptor (AT1R) pathway is activated in mice with chronic pressure overload (CPO). When this activation is combined with high salt intake, it leads to sympathoexcitation, hypertension, and left ventricular (LV) dysfunction. Salt intake is thus an important factor that contributes to heart failure. Miso, a traditional Japanese food made from fermented soybeans, rice, wheat, or oats, can attenuate salt-induced hypertension in rats. However, its effects on CPO mice with salt-induced sympathoexcitation and LV dysfunction are unclear. Here, we investigated whether miso has protective effects in these mice. We also evaluated mechanisms associated with the hypothalamic MR-AT1R pathway. Aortic banding was used to produce CPO, and a sham operation was performed for controls. At 2 weeks after surgery, the mice were given water containing high NaCl levels (0.5%, 1.0%, and 1.5%) for 4 weeks. The high salt loading in CPO mice increased excretion of urinary norepinephrine (uNE), a marker of sympathetic activity, in an NaCl concentration-dependent manner; however, this was not observed in Sham mice. Subsequently, CPO mice were administered 1.0% NaCl water (CPO-H) or miso soup (1.0% NaCl equivalent, CPO-miso). The expression of hypothalamic MR, serum glucocorticoid-induced kinase-1 (SGK-1), and AT1R was higher in the CPO-H mice than in the Sham mice; however, the expression of these proteins was attenuated in the CPO-miso group. Although the CPO-miso mice had higher sodium intake, salt-induced sympathoexcitation was lower in these mice than in the CPO-H group. Our findings indicate that regular intake of miso soup attenuates salt-induced sympathoexcitation in CPO mice via inhibition of the hypothalamic MR-AT1R pathway.
authors.forename: Koji
authors.initials: K
authors.lastname: Ito
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Hirooka
authors.forename: Kenji
authors.initials: K
authors.lastname: Sunagawa
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000503:physiopathology*; D008297:Male; D051379:Mice; D044139:Receptor, Angiotensin, Type 2; D018161:Receptors, Mineralocorticoid / Q000502:physiology*; D012965:Sodium Chloride; D013025:Glycine max; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000503:physiopathology*; D018487:Ventricular Dysfunction, Left / Q000178:diet therapy* / Q000209:etiology
chemical_list: D044139:Receptor, Angiotensin, Type 2; D018161:Receptors, Mineralocorticoid; D012965:Sodium Chloride