Vascular effects and antihypertensive properties of κ-casein macropeptide

The blood-pressure-lowering effect of bovine κ-casein macropeptide (CMP), previously reported to exhibit a modest angiotensin-converting enzyme (ACE)-inhibitory activity in vitro, was evaluated in spontaneously hypertensive rats (SHR). The oral administration of CMP (150 mg kg−1) significantly reduced the systolic blood pressure (SBP) of SHR. The antihypertensive action was more pronounced when CMP was treated with trypsin. The sequence MAIPPKK, identified in the tryptic hydrolysate of bovine CMP, significantly reduced blood pressure at a dose of 10 mg kg−1. The CMP and its tryptic peptides induced relaxation of endothelium-intact aortic rings. The sequence MAIPPKK also evoked a significant relaxation effect; however, the shorter sequence MAIPPK and the strong ACE-inhibitory tripeptide IPP exhibited a vascular relaxing effect lower than 10%. The implications of vascular relaxing mechanisms, as well as the possibility that the tripeptide IPP is at least partially responsible for the antihypertensive effects of CMP, are discussed.