Abstract

We newly manufactured miso rich in angiotensin-converting enzyme (ACE) inhibitory activity (Marukome MK-34-1, shinki miso) and investigated its antihypertensive properties in rat models of genetic hypertension. ACE inhibitory activity was tenfold higher in shinki miso than in commercially available Marukome Nenrin miso (nenrin miso). The inhibitory activity of shinki miso was confined to <3 kDa fractions and was detected in several fractions with high polarity by C18 high-performance liquid chromatography. Systolic blood pressure (SBP) increased age-dependently in stroke-prone spontaneously hypertensive rats (SHRSP/Izm) given a 0.6% (w/v) NaCl solution (salt solution group) that matched the salt content of the miso solutions. This SBP increase was attenuated in both the 5% nenrin and 5% shinki miso solution groups compared to the salt solution group. The reduction in SBP was greater in rats fed shinki than in rats fed nenrin miso. Similarly, in a salt-induced hypertension model with Dahl rats, the 5% nenrin miso solution attenuated the rising SBP observed in the salt solution group. Moreover, combining 5% nenrin miso with 5% shinki miso (2:1, v/v) (awase miso group) significantly decreased the SBP per gram salt intake by 8% compared with the nenrin miso treatment. However, there were no differences in urinary Na excretion between the nenrin and awase miso groups. In conclusion, we produced a new miso with potent ACE inhibitory activity that reduced spontaneous and salt-induced hypertension. These results suggest that salt sensitivity is decreased by the addition of shinki miso to nenrin miso.

Highlights

  • Miso is a traditional Japanese food whose consumption dates to 700 AD

  • We further analyzed this fraction by C18 reversedphase high-performance liquid chromatography (HPLC) and found that the inhibitory activity was present in higher-polarity fractions of shinki miso extract but was limited to fraction 5 of nenrin miso (Fig. 2)

  • We found several dipeptides with angiotensin-converting enzyme (ACE) inhibitory activity in HPLC-MS/NMR analysis

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Summary

Introduction

Miso is a traditional Japanese food whose consumption dates to 700 AD. It is usually produced from soybeans with malted rice and salt. We recently demonstrated that miso soup attenuates saltinduced hypertension in Dahl rats prone to salt-induced hypertension (Dahl S rats) [1, 2]. This was attributed to natriuresis or vasodilation induced by miso soup ingredients. In a human intervention trial, two daily servings of miso soup (3.8 g salt/day) for 3 months did not affect the systolic blood pressure (SBP) or diastolic blood pressure (DBP) of subjects with normotension or stage 1 hypertension [4]. A 5-year crosssectional observation found no association between the frequency of miso soup intake and the SBP and DBP of subjects with normal or high normal BP [5]

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