Water is essential to life processes and has a number of significant functions. The ingredients of drinking water as well as nutrients in foodstuffs are now considered important to people's health. Deep-sea water in particular has started to receive attention for its rich inorganic nutrients such as Mg, Ca, and K 1,2) which are due mainly to less photosynthesis of plant plankton and much organic decomposition. In addition to the beneficial effects of these minerals on the cardiovascular system, unknown effects of some ultratrace elements or unknown substances in deep-sea water may be found in future. Some scientific evidences of therapeutic or preventive effects of deep-sea water have been reported recently. Deepsea water improved mineral imbalances and atopic eczema/ dermatitis syndrome in humans 2) and was effective in the prevention of hyperlipidemia and atherosclerosis in cholesterol-fed rabbits. 3,4) We expect that the continuous intake of deep-sea water could prevent hypertension as well as hypercholesterolemia, because investigators have revealed that oral supplementation of calcium 5,6) or magnesium 7,8) to hypertensive patients lowered blood pressure in addition to reducing the serum total cholesterol level. 7)Hypercholesterolemia and hypertension occur due to genetic as well as dietary factors. The Kurosawa and KusanagiHypercholesterolemic (KHC) rabbit is an animal model of spontaneous hypercholesterolemia (Type IIa) and atherosclerosis established by inbreeding a mutant of the Japanese White rabbit discovered by Japan Laboratory Animals, Inc. in 1985.9) The KHC rabbit is deficient in LDL-receptors in the liver and shows an abnormally increased LDL-cholesterol level without unusual deposits of fat in some organs.9) Atherosclerosis develops in the aortic arch and around bifurcations of the main branch arteries by the age of 3 months.9) We also reported previously that young adult KHC rabbits aged 10-12 months showed mild hypertension compared to agematched normal rabbits in addition to hypercholesterolemia, though atherosclerotic lesions were relatively in the earlystage. 10,11) The mild hypertension is thought to be independent of hypercholesterolemia.11) Intervention of either hypercholesterolemia or hypertension is considered to be inadequate to prevent progression of atherosclerosis and related cardiovascular events if hypertension and hypercholesterolemia coexist.12) Ca and Mg in deep-sea water could suppress absorption of cholesterol in the small intestine in cholesterol-fed rabbits, which might contribute to anti-hypercholesterolemic action of deep-sea water.3,4) Therefore, it is appropriate to use spontaneous hypercholesterolemic rabbits.In the present study, we investigated the effect of the intake of refined deep-sea water at a degree of hardness of 1000 for 6 months on hypercholesterolemia and mild hypertension in KHC rabbits aged 4 months, at which time atherosclerosis starts to occur in the ascending aorta and around orifices of branch arteries, by measuring serum and plasma biochemical par...

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In a previous study, we isolated the inhibitory peptide (P4 peptide, Gly-Phe-Hyp-Gly-Thr-Hyp-Gly-Leu-Hyp-Gly-Phe) for angiotensin I-converting enzyme (ACE) from chicken breast muscle extract possessing hypotensive activity for spontaneously hypertensive rats (SHRs). This study was performed to elucidate the peptide's action mechanisms of inhibiting ACE. Intravenous administration of synthetic P4 peptide resulted in significant drops in the blood pressures of SHRs. As Dixon plots indicate, the P4 peptide showed high affinity toward ACE (K(i) = 11.48 microM) and only 10% of the total amount of the P4 peptide was decomposed. The analyses of the relationship between the ACE inhibitory activity and structure of the P4 peptide clarified that Hyp-Gly-Leu-Hyp-Gly-Phe showed a stronger activity (IC50 = 10 microM) than the P4 peptide (IC50 = 46 microM). When Phe at the C-terminus of the P4 peptide was deleted, IC50 changed to 25000 microM, indicating that Phe at the C-terminus of the peptide is very important for ACE inhibitory activity.

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