Accumulation of ACE Inhibitory Tripeptides, Val-Pro-Pro and Ile-Pro-Pro, in Vascular Endothelial Cells

Abstract

The antihypertensive peptides, Val-Pro-Pro and Ile-Pro-Pro, were successfully detected in the aorta of spontaneously hypertensive rats after orally administering these peptides by a guanidine-thiocyanate treatment to prevent proteolysis. Cy3-labeled versions of both peptides were localized in the endothelial cells of arterial vessels in the rats. The accumulation of both peptides in the endothelial cells suggested in vivo inhibitory activity of the angiotensin I-converting enzyme.

Milk and milk‐derived peptides combat against hypertension and vascular dysfunction: a review

“…Jauhiainen et al (2007) administered radio-labelled Ile-Pro-Pro to spontaneously hypertensive rats (SHR) both intravenously and orally and subsequently radioactivity was detected in aorta, heart and kidneys for as long as 48 h after their administration. Kawaguchi et al (2012) detected labelled Ile-Pro-Pro and Val-Pro-Pro in the endothelium of rats after oral administration of these compounds. They also measured Ile-Pro-Pro and Val-Pro-Pro concentrations in plasma and tissues; liver, kidneys, lung and aorta (concentrations from lowest to highest).…”

“…Bioavailability of food-derived components, that is, their absorption from intestine to the systemic circulation is an important issue when examining the physiological effects of nutrients. Ile-Pro-Pro, Leu-Pro-Pro and Val-Pro-Pro have been detected in the circulation after oral administration of dairy products enriched with these peptides both in experimental and human studies (Jauhiainen et al, 2007;van der Pijl et al, 2008;Kawaguchi et al, 2012;Gleeson et al, 2017). The levels of the detected tripeptides are low; however, but there were some indications that there was an accumulation of peptides in blood pressure regulating organs.…”

“…Kawaguchi et al . () detected labelled Ile‐Pro‐Pro and Val‐Pro‐Pro in the endothelium of rats after oral administration of these compounds. They also measured Ile‐Pro‐Pro and Val‐Pro‐Pro concentrations in plasma and tissues; liver, kidneys, lung and aorta (concentrations from lowest to highest).…”

Preparation, Bioavailability, and Mechanism of Emerging Activities of Ile‐Pro‐Pro and Val‐Pro‐Pro

“…IPP and VPP have been shown to improve endothelial function in isolated SHR mesenteric arteries (Jakala, Pere et al., ; Jakala, Hakala et al., ). Cy3‐labeled both of IPP and VPP shown that both peptides existed in the endothelial cells of blood vessels in the SHRs and this accumulation could act as ACE inhibitor after oral administration (Kawaguchi, Nakamura, Kamiie, Takahashi, & Yamamoto, ). In cultured vascular endothelial cells and isolated aortic rings, IPP and VPP could stimulate the production of vasorelaxant substances (that is, NO and EDHF) through B2 receptor (Hirota et al., ).…”

Biologically Active Peptides Released From Food Proteins

“…Znaczną większość bioaktywnych peptydów stanowią krótkie fragmenty -di-oraz tripeptydy (np. duża część inhibitorów ACE), które mogą przekraczać barierę jelitową i docierać w postaci niezmienionej do miejsca oddziaływania, a następnie wpływać na funkcje fizjologiczne organizmu [41,96]. Wchłanianie peptydów przez jednowarstwowe komórki nabłonka jelitowego może odbywać się w różny sposób [88].…”