Antihypertensive effect of heshiko, a fermented mackerel product, on spontaneously hypertensive rats

Abstract

During the processing of heshiko, a fermented mackerel product, a rapid increase in peptide content in the extract and a remarkable decrease in the IC₅₀ (the inhibitor concentration to inhibit 50% of enzyme activity) as an index of the angiotensin l-converting enzyme (ACE) inhibitory activity were observed. Systolic blood pressure (SBP) in spontaneously hypertensive rats (SHR) decreased between 2 and 4 h after single oral administration of heshiko extract at a dose of 10 mg/kg as a peptide, and SBP recovered its initial level by 8 h. For single doses of extract at three different levels (5, 10 and 50 mg/kg), SBP similarly decreased after between 2 and 4 h. The decreased SBP at 50 mg/kg was almost equal to that at 10 mg/kg, indicating a low dose dependency for heshiko extract. Through successive administration of heshiko extract or its desalted extract at 1 mg/kg for 10 days, SBP decreased 7 days after the start of administration and it recovered its initial level 5 days after stopping administration. During these periods, the change in ACE activity in blood plasma from SHR administered the extract roughly corresponded to that of SBP, suggesting that ACE inhibition was related to a decrease in SBP. For long-term administration of the extract to 5-week-old SHR for 70 days, SBP decreased 28 days after the start of administration. The decreased SBP remained low for 28 days after stopping administration, whereas the decreased ACE activity recovered its initial level. These results suggest that heshiko extract influences not only ACE inhibition, but also other systems that regulate blood pressure.