Long-term intake of milk peptides attenuates development of hypertension in spontaneously hypertensive rats

J Physiol Pharmacol. 2001 Dec;52(4 Pt 2):745-54.


Effect of long-term intake of isoleucine-proline-proline (IPP) and valine-proline-proline (VPP), or a sour milk product containing these peptides on development of hypertension was investigated in spontaneously hypertensive rats (SHR). Six-week-old SHR were given: 1) water (control group), 2) IPP and VPP dissolved in water (peptide group) or 3) sour milk containing IPP and VPP (sour milk group) for 12 weeks. Systolic blood pressure (SBP) was measured by tail-cuff method. Development of hypertension was attenuated in the groups receiving tripeptides or sour milk as compared to the control group. At the end of treatment period, SBP was 176 +/- 1 mmHg in sour milk group, 181 +/- 2 mmHg in peptide group, and 193 +/- 1 mmHg in control group (P < 0.001). After treatment withdrawal, SBP rose gradually reaching the level of control group within four weeks' follow-up. In functional bioassay of ACE inhibitory activity, effect of the tripeptides on angiotensin I or angiotensin II-induced contraction in rat mesenteric arteries was evaluated. IPP inhibited the angiotensin I-induced contraction, whereas the angiotensin II-induced contraction remained unaltered. In conclusion, long-term intake of IPP and VPP, or a sour milk containing these tripeptides attenuated the development of hypertension in SHR. One possible mechanism underlying this effect is ACE inhibition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin-Converting Enzyme Inhibitors / pharmacology
  • Angiotensins / pharmacology
  • Animals
  • Antihypertensive Agents / administration & dosage*
  • Biological Availability
  • Female
  • Hypertension / prevention & control*
  • Male
  • Mesenteric Arteries / drug effects
  • Mesenteric Arteries / physiology
  • Milk Proteins / administration & dosage*
  • Oligopeptides / administration & dosage*
  • Rats
  • Rats, Inbred SHR
  • Rats, Wistar


  • Angiotensin-Converting Enzyme Inhibitors
  • Angiotensins
  • Antihypertensive Agents
  • Milk Proteins
  • Oligopeptides