A Flounder Fish Peptide Shows Anti-Hypertensive Effects by Suppressing the Renin-Angiotensin-Aldosterone System and Endothelin-1

Background: Many fishes have been known for their good nutritional effects especially in the cardiovascular aspect. Some specific fish peptides have anti-hypertensive effects. Objective: In the present study, we hypothesized that the hexapeptide (MEVFVP) from flounder fish muscle can be a potent antihypertensive peptide, therefore, decided to perform this experiment. Methods: The peptide MEVFVP from flounder fish muscle (40 mg/kg) and vehicle were administered per os to spontaneously hypertensive rats (SHRs) (SHR-M and SHR-C, respectively). Additionally, plasma MEVFVP was measured serially before and after its oral administration to Sprague Dawley rats. Results: Blood pressures (BPs), especially systolic BP, in SHR rats were decreased around 3-6 hours after MEVFVP administration. Compared with SHR-C rats, endothelin-1 (ET-1) mRNA expression in multiple tissues, and plasma levels of ET-1, angiotensin II, and aldosterone were lower in SHR-M rats, whereas the phosphorylation of AMP-activated protein kinase (AMPK) was increased in the kidney of SHR-M rats. The administered peptide was not detected in rat plasma, while ex vivo incubation of the peptide in rat plasma caused its rapid degradation within minutes. Conclusion: Our results show that the MEVFVP has an antihypertensive effect by regulating renin- angiotensin-aldosterone system, ET-1 and AMPK despite its limited bioavailability.