Casein-derived tripeptide Ile–Pro–Pro improves angiotensin-(1–7)- and bradykinin-induced rat mesenteric artery relaxation

Abstract

AimsMilk casein-derived bioactive tripeptides isoleucine–proline–proline (Ile–Pro–Pro) and valine–proline–proline (Val–Pro–Pro) lower blood pressure in animal models of hypertension and humans. In some studies, their angiotensin-converting enzyme (ACE)-inhibitory effect has been demonstrated. Besides classical ACE-angiotensin II-AT1-receptor pathway (ACE-Ang II- AT1), the significance of ACE2-angiotensin-(1–7)-Mas-receptor (ACE2-Ang-(1–7)-Mas) axis in the blood pressure regulation has now been acknowledged. The present study was aimed to further evaluate the renin–angiotensin system (RAS)-related vascular effects of Ile–Pro–Pro in vitro using rat mesenteric arteries. Main methodsSuperior mesenteric arteries of spontaneously hypertensive rat (SHR) were isolated, cut into rings and mounted in standard organ bath chambers. Endothelium-intact arterial rings were incubated in Krebs solution either with Ile–Pro–Pro, proline–proline (Pro–Pro), isoleucine (Ile), proline (Pro) or captopril for 6h at +37°C and vascular reactivity was measured. Key findingsIn the presence of AT1-antagonist valsartan, Ang II induced vasodilatation, which was more pronounced in the arteries incubated with Ile–Pro–Pro (P<0.05) compared to the other compounds. Ang-(1–7)-induced vasodilatation was augmented by Ile–Pro–Pro or Pro (P<0.001 vs. control). Mas-receptor antagonist A-779 did not alter the responses. Ile–Pro–Pro and Pro augmented also bradykinin-induced relaxations (P<0.001 vs. control). Control arteries and arteries incubated with captopril showed only slight relaxations at higher bradykinin concentrations. SignificanceCasein-derived tripeptide Ile–Pro–Pro and amino acid Pro enhance the vasodilatory effect of Ang-(1–7) and bradykinin. The role of ACE2-Ang–(1–7)-Mas axis in the modulation of vascular tone by these compounds seems probable.