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Milk protein-derived tripeptides improve endothelium dependent vasodilatation; Do bradykinin and mas-receptors play a role? Milk casein-derived tripeptides (Ile-Pro-Pro, Val-Pro-Pro and Leu-Pro-Pro) and functional food products containing them lower blood pressure in experimental models of hypertension (spontaneously hypertensive rats, salt-loaded Goto-Kakizaki rats, transgenic rats harboring human renin and angiotensinogen genes) (Jäkälä and Vapaatalo, 2010) and in mildly hypertensive subjects (Turpeinen et. al, 2012) and improve vascular relaxation ex vivo and in vivo. The mechanism of the antihypertensive effect has been suggested to be related to ACE1-inhibition and reduced formation of the potent vasoconstrictor, angiotensin II (Ang II). However, ACE-1 inhibition and lowering of blood pressure do not explain – at least alone - the improved endothelial function. We present here data from in vitro experiments which show that Ile-Pro-Pro pretreatment augments bradykinin-induced vasorelaxation. This effect can be abolished by an antagonist (A-779) of the recently described mas-receptor, a receptor for a vasodilatory component Ang(1-7) in renin-angiotensin-system (RAS) (Ehlers et. al, 2011). In addition, inhibition of arginase by Ile-Pro-Pro (Lehtinen et. al, 2010) increases availability of arginine, the substrate for endothelial nitric oxide synthase (eNOS) and thus the production of vasodilatory and endothelium protecting endogenous nitric oxide (NO). The presented novel hypotheses for mechanisms of improved endothelial function by the bioactive tripeptides remain to be confirmed in man. References: Jäkälä P. & Vapaatalo H.(2010). Pharmaceuticals 3:251-272. Turpeinen AM et. al.(2012) Annals of Medicine: DOI: 10.3109/07853890.2012.663926. Ehlers PI et. al. (2011) Life Sciences 88:206-211. Lehtinen R. et. al. (2010) Arznelmittelforschung/Drug Research 60:182-185. Supported by: The Finnish Funding Agency for Technology and Innovations (TEKES)
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