Acute effect of whey peptides upon blood pressure of hypertensive rats, and relationship with their angiotensin-converting enzyme inhibitory activity

Mol Nutr Food Res. 2012 Feb;56(2):316-24. doi: 10.1002/mnfr.201100381. Epub 2011 Dec 7.


Scope: The aim of this study was to investigate the antihypertensive effect of a peptide fraction (PepC) obtained from a whey protein concentrate following hydrolysis by Cynara cardunculus, as well as of its fraction with MW below 3 kDa (PepCF). Both these concentrates encompassed peptides that exhibited potent in vitro inhibition of angiotensin-converting enzyme (ACE): two were released from α-lactalbumin--KGYGGVSLPEW and DKVGINYW, and one from β-lactoglobulin--DAQSAPLRVY.

Methods and results: Upon oral administration, by gastric intubation, of 400 mg/kg body weight (bw) of those peptide concentrates, or 5 mg/kg bw of the corresponding synthetic peptides, to 12 wk-old spontaneously hypertensive rats (SHR), the systolic and diastolic blood pressures were monitored by the tail-cuff method--before, and 2, 4, 6, 8 and 24 h afterwards. Water and zofenopril (5 mg/kg bw)--a known ACE-inhibitor, were used as negative and positive controls, respectively. Acute administration of PepC, PepCF, KGYGGVSLPEW, DKVGINYW and DAQSAPLRVY caused antihypertensive effects in SHR; the maximum effect occurred by 4 h and 6 h after administration of the peptide concentrates and the synthetic peptides, respectively. PepC and KGYGGVSLPEW also showed ACE-inhibitory activity in vivo: the pressor effect of angiotensin I was significantly lower, and the response to bradykinin increased when the rats were pre-treated with either product.

Conclusion: Our results strongly suggest that PepC will be effective as nutraceutical ingredient for the formulation of functional foods aimed at hypertension control.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Angiotensin I / pharmacology
  • Animals
  • Antihypertensive Agents / pharmacology*
  • Blood Pressure / drug effects*
  • Bradykinin / pharmacology
  • Lactalbumin / chemistry
  • Lactoglobulins / chemistry
  • Male
  • Milk Proteins / chemistry*
  • Peptide Fragments / pharmacology
  • Peptides / pharmacology*
  • Peptidyl-Dipeptidase A / metabolism*
  • Rats
  • Rats, Inbred SHR
  • Whey Proteins


  • Antihypertensive Agents
  • Lactoglobulins
  • Milk Proteins
  • Peptide Fragments
  • Peptides
  • Whey Proteins
  • Lactalbumin
  • Angiotensin I
  • Peptidyl-Dipeptidase A
  • Bradykinin