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Protein Pept Lett ; 28(7): 831-840, 2021.
Article in English | MEDLINE | ID: mdl-33573539

ABSTRACT

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.


Subject(s)
Antihypertensive Agents/pharmacology , Endothelin-1/genetics , Fish Proteins/pharmacology , Flounder/metabolism , Hypertension/drug therapy , Oligopeptides/pharmacology , Renin-Angiotensin System/drug effects , AMP-Activated Protein Kinases/genetics , AMP-Activated Protein Kinases/metabolism , Administration, Oral , Aldosterone/metabolism , Amino Acid Sequence , Angiotensin II/genetics , Angiotensin II/metabolism , Animals , Antihypertensive Agents/isolation & purification , Antihypertensive Agents/pharmacokinetics , Blood Pressure/drug effects , Endothelin-1/antagonists & inhibitors , Endothelin-1/metabolism , Fish Proteins/isolation & purification , Fish Proteins/pharmacokinetics , Gene Expression Regulation , Hypertension/genetics , Hypertension/metabolism , Hypertension/physiopathology , Kidney/drug effects , Kidney/metabolism , Kidney/physiopathology , Male , Muscles/chemistry , Oligopeptides/isolation & purification , Oligopeptides/pharmacokinetics , Rats , Rats, Inbred SHR , Rats, Sprague-Dawley , Renin-Angiotensin System/genetics , Signal Transduction
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