Formation of the potent vasoconstrictor Angiotensin II is blocked by ACE-inhibitors used in the standard treatment of hypertension. Clinically used ACE-inhibitors exhibit a structural similarity to naturally occurring small peptides. We have identified the dipeptide IW (IC₅₀=0.7mM) from whey protein as a potent ACE inhibitor and tested this potential under in vivo conditions.

Methods: 

Spontaneously hypertensive rats (SHR) were fed with food pellets augmented with Captopril (CA 68mg/kg/day), IW (20mg/kg/day), a peptide mixture (0.77g/kg/day, containing IW) or none (control) for 14 weeks. The systolic blood pressure (SBP) was measured twice weekly. Direct vasodilatory effects as well as indirect effect (via ACE inhibition) of CA and IW were investigated ex vivo using isolated rat aortic rings in a Mulvany myograph.

Results: 

CA significantly decreased SBP by -55±8 mmHg versus control after 14 weeks. IW lowered SBP by -44±5 mmHg and the peptide mix by -41±9 mmHg. Ex vivo aortic vessel wall tension was neither affected by IW nor CA. However after incubation of aorta with CA or IW conversion of exogenous Angiotensin I to Angiotensin II was significantly reduced and vasoconstriction was blunted.

Conclusions: 

IW is similar effective as CA to lower blood pressure in SHR. This effect is most likely mediated by its effect on ACE, because IW does not exert directly modulate vessel tone but inhibits the conversion of exogenous Angiotensin I to Angiotensin II. We conclude that IW or whey products containing IW may be used as nutrition additives in daily life to lower in vivo ACE activity.