Identification and characterization of novel angiotensin-converting enzyme inhibitors obtained from goat milk.
The aim of the present study was to identify and characterize new inhibitory peptides of angiotensin I-converting enzyme (ACE) from goat milk and to analyze the effect of long-term intake of a goat milk hydrolysate-supplemented (GP-hyd) diet on the development of hypertension in spontaneously hypertensive rats (SHR). Three new inhibitory peptides for ACE (TGPIPN, SLPQ, and SQPK) were isolated. The inhibitory concentration 50% (IC50) values of individual peptides were 316, 330, and 354 micromol/L, respectively. Only TGPIPN was found to pass intact a monolayer of Caco-2 cells in small amounts. The SHR fed for 12 wk a diet (GP-hyd) enriched in a hydrolysate containing these peptides (estimated intake of TGPIPN was 230 mg/kg per d) showed lower (approximately 15 mmHg) systolic blood pressure than animals fed a control diet. The ACE activities in the aorta, left ventricle, and kidney were significantly decreased in the GP-hyd group compared with those of the control group and were similar to those found in SHR fed captopril (130 mg/kg per d). Impaired endothelium-dependent relaxation to acetylcholine by aortic rings from SHR was improved in those fed the GP-hyd diet. The left ventricle weight and kidney weight index were significantly reduced in the GP-hyd group and captopril groups. Moreover, long-term treatment of SHR with a diet enriched in goat milk hydrolysate, or captopril, attenuated the development of hypertension, cardiac and renal hypertrophy, and endothelial dysfunction. These effects might be related to the in vivo inhibitory effects of the hydrolysate on tissue ACE activity.
Geerlings
A
A
Department of Biomedicine, Puleva Biotech, Camino de Purchil 66, 18004 Granada, Spain. ageerlings@pulevabiotech.es
Villar
I C
IC
Hidalgo Zarco
F
F
Sánchez
M
M
Vera
R
R
Zafra Gomez
A
A
Boza
J
J
Duarte
J
J
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000302:isolation & purification* / Q000494:pharmacology*; D000821:Animal Feed / Q000032:analysis; D000818:Animals; D001011:Aorta / Q000187:drug effects; D018938:Caco-2 Cells; D002216:Captopril / Q000008:administration & dosage / Q000494:pharmacology; D004032:Diet; D006041:Goats; D006352:Heart Ventricles / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000209:etiology; D020128:Inhibitory Concentration 50; D007668:Kidney / Q000187:drug effects; D008297:Male; D008892:Milk / Q000737:chemistry*; D008894:Milk Proteins / Q000737:chemistry*; D051381:Rats; D011918:Rats, Inbred SHR
D000806:Angiotensin-Converting Enzyme Inhibitors; D008894:Milk Proteins; D002216:Captopril