title: The influence of dietary peptide inhibitors of angiotensin-converting enzyme on the hypotensive effects of enalapril.
abstract: BACKGROUND
  Enalapril is an antihypertensive medicine that inhibits angiotensin I-converting enzyme (ACE). The present study investigated interactions between enalapril and a fermented milk product (FMP) containing the ACE-inhibitory peptides, Val-Pro-Pro (VPP) and Ile-Pro-Pro (IPP).
  
  
  METHODS
  Single-dose and long-term (6-week) in vivo studies were used to investigate the effects of enalapril and FMP on blood pressure in spontaneously hypertensive rats.
  
  
  RESULTS
  Single-dose oral administration of concomitant enalapril and FMP (VPP, IPP: 3.5 mg/kg) produced a lower antihypertensive effect than enalapril monotherapy. However, this effect was not observed in animals administered a lower dose of FMP (VPP, IPP: 1.75 mg/kg) along with enalapril. In rats administered enalapril concomitantly with a fish protein product (FPP) containing a different ACE inhibitory peptide (Leu-Lys-Pro-Asn-Met), significant attenuation of the antihypertensive effect was also observed 1 and 2 h after administration, as compared to enalapril monotherapy. During a 6-week oral administration study, the enalapril monotherapy group showed significant antihypertensive effects compared to those observed in the controls on day 28. Oral administration of enalapril and FMP, with a 1-h interval between doses, resulted in significant antihypertensive effects on day 35, indicating a delayed onset in comparison to enalapril monotherapy. In rats receiving enalapril monotherapy for 28 days, followed by 14 days of concomitant FMP, significant antihypertensive effects were observed after day 35, and these did not differ significantly from the effects observed during enalapril monotherapy.
  
  
  CONCLUSIONS
  The present findings suggested that long-term concomitant intake of FMP and enalapril could influence the antihypertensive effects of this drug.
authors.affiliation: Laboratory of Clinical Pharmaceutics, Faculty of Pharma Sciences, Teikyo University, Kaga 2-11-1, Itabashi-ku, Tokyo, 173-8605 Japan.
authors.forename: Machiko
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: Laboratory of Medical Pharmacology, Faculty of Pharma Sciences, Teikyo University, Kaga 2-11-1, Itabashi-ku, Tokyo, 173-8605 Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Kurihara
authors.affiliation: Laboratory of Medical Pharmacology, Faculty of Pharma Sciences, Teikyo University, Kaga 2-11-1, Itabashi-ku, Tokyo, 173-8605 Japan.
authors.forename: Shigeto
authors.initials: S
authors.lastname: Suzuki
authors.affiliation: Laboratory of Clinical Pharmaceutics, Faculty of Pharma Sciences, Teikyo University, Kaga 2-11-1, Itabashi-ku, Tokyo, 173-8605 Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Nagashima
authors.affiliation: Laboratory of Clinical Pharmaceutics, Faculty of Pharma Sciences, Teikyo University, Kaga 2-11-1, Itabashi-ku, Tokyo, 173-8605 Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Hosono
authors.affiliation: Laboratory of Clinical Pharmaceutics, Faculty of Pharma Sciences, Teikyo University, Kaga 2-11-1, Itabashi-ku, Tokyo, 173-8605 Japan.
authors.forename: Fumio
authors.initials: F
authors.lastname: Itagaki
keywords: Angiotensin I-converting enzyme inhibitor; Concomitant administration; Drug interaction; Enalapril; Fermented milk; Foods for specified health uses; Hypertension; Peptide
references.citation: Am J Clin Nutr. 1996 Nov;64(5):767-71
references.pmid: 8901799
references.citation: J Physiol Pharmacol. 2001 Dec;52(4 Pt 2):745-54
references.pmid: 11785770
references.citation: Am J Hypertens. 2005 Dec;18(12 Pt 1):1600-5
references.pmid: 16364832
references.citation: J Dairy Sci. 1995 Apr;78(4):777-83
references.pmid: 7790570
references.citation: J Am Coll Nutr. 2005 Aug;24(4):257-65
references.pmid: 16093403
references.citation: Am J Clin Nutr. 2003 Feb;77(2):326-30
references.pmid: 12540390
references.citation: J Hum Hypertens. 2004 Nov;18(11):795-802
references.pmid: 15175633
references.citation: Biosci Biotechnol Biochem. 2002 Feb;66(2):378-84
references.pmid: 11999412
references.citation: Nutrition. 2008 Oct;24(10):933-40
references.pmid: 18562172
references.citation: J Nutr. 1996 Dec;126(12):3063-8
references.pmid: 9001375
references.citation: Food Nutr Res. 2008;52:null
references.pmid: 19109662
references.citation: Biosci Biotechnol Biochem. 1996 Mar;60(3):488-9
references.pmid: 8901109
references.citation: Am J Hypertens. 2004 Aug;17(8):701-6
references.pmid: 15288885
references.citation: J Mol Recognit. 2009 Mar-Apr;22(2):162-8
references.pmid: 18816584
references.citation: Hypertension. 2008 Feb;51(2):399-405
references.pmid: 18086944
references.citation: Biochim Biophys Acta. 1995 May 24;1236(1):31-8
references.pmid: 7794953
references.citation: Br J Nutr. 2005 Jul;94(1):84-91
references.pmid: 16115337
references.citation: J Med Food. 2005 Winter;8(4):423-30
references.pmid: 16379551
references.citation: J Hum Hypertens. 2011 Jul;25(7):425-36
references.pmid: 20811398
references.citation: J Pharmacol Exp Ther. 2008 Nov;327(2):432-41
references.pmid: 18713951
references.citation: Life Sci. 2006 Nov 25;79(26):2492-8
references.pmid: 16959271
references.citation: Biosci Biotechnol Biochem. 2001 Jan;65(1):1-13
references.pmid: 11272811
references.citation: J Dairy Sci. 1995 Jun;78(6):1253-7
references.pmid: 7673515
references.citation: Immunopharmacology. 1999 Oct 15;44(1-2):123-7
references.pmid: 10604535
references.citation: Heart Vessels. 2011 Sep;26(5):549-56
references.pmid: 21221598
references.citation: J Dairy Res. 2002 Feb;69(1):103-11
references.pmid: 12047101