Milk protein-derived bioactive tripeptides Ile-Pro-Pro and Val-Pro-Pro protect endothelial function in vitro in hypertensive rats

Milk products containing casein-derived bioactive tripeptides Ile-Pro-Pro (isoleucine-proline-proline) and Val-Pro-Pro (valine-proline-proline) have been shown to lower blood pressure in animal models and clinical studies. In vitro experiments were performed to elucidate the effects of Ile-Pro-Pro, Val-Pro-Pro and Leu-Pro-Pro (leucine-proline-proline) on vascular function. Isolated spontaneously hypertensive rat (SHR) mesenteric arteries were stored in Krebs solution containing 1 mM of tripeptides at +4 °C for 1, 12 or 24 h. Thereafter, arteries were mounted in an organ bath chamber (+37 °C) for vascular reactivity measurements. Endothelium-dependent relaxation was better preserved (P < 0.05) in mesenteric arteries stored with tripeptides versus the control. Endothelium-independent relaxation remained unaltered. Endothelium-derived hyperpolarizing factor (EDHF)-related relaxation was more pronounced in arteries stored with Ile-Pro-Pro. Angiotensin-converting enzyme (ACE)-inhibitory activity of tripeptides was demonstrated after 24 h storage suggesting its role in improved relaxation. Thus, tripeptides do not affect smooth muscle but they protect endothelium in cold storage.