Casein-derived bioactive tripeptides Ile-Pro-Pro and Val-Pro-Pro attenuate the development of hypertension and improve endothelial function in salt-loaded Goto–Kakizaki rats

Increased blood pressure and plasma cholesterol concentration are the major risk factors for cardiovascular diseases. We have previously shown that fermented milk products containing casein-derived bioactive tripeptides, isoleucine-proline-proline (Ile-Pro-Pro) and valine-proline-proline (Val-Pro-Pro) partly inhibit the blood pressure increase in spontaneously hypertensive rats (SHR). In the present study, we investigated the effect of bioactive tripeptide-containing fermented milk products (with or without plant sterols) on blood pressure and vascular function in salt-loaded type 2 diabetic Goto–Kakizaki (GK) rats after 8 weeks’ treatment. The development of blood pressure was attenuated in the groups receiving tripeptide-containing products (−10 to −12 mmHg vs. the control product group, P < 0.01). Tripeptide-containing products enhanced the impaired endothelium-dependent relaxation of mesenteric arteries. Also the role of endothelium-derived hyperpolarizing factor (EDHF) was demonstrated. Interestingly, pretreatment of arterial rings with verapamil normalized the impaired endothelial function. Endothelium-independent relaxations were similar between the groups. Furthermore, tripeptides had positive effects on renin–angiotensin–aldosterone system.