Journal of Food and Nutrition Research
ISSN (Print): 2333-1119 ISSN (Online): 2333-1240 Website: https://www.sciepub.com/journal/jfnr Editor-in-chief: Prabhat Kumar Mandal
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Journal of Food and Nutrition Research. 2023, 11(8), 519-524
DOI: 10.12691/jfnr-11-8-1
Open AccessArticle

Endothelium-Dependent Vasorelaxant Effect of a Bioactive Tripeptide, Valine-Proline-Proline, on Rat Aortic Rings

Jair Lozano-Cuenca1, Oscar Alberto López-Canales2, Ángel Miliar-García3, María de los Ángeles Martínez–Godínez3, Osiris Teran-Gallardo3, María Cristina Paredes-Carbajal2, Ruth Mery López-Mayorga3, Enrique Fernando Castillo-Henkel3, Héctor Flores-Herrera4 and Jorge Skiold López-Canales1, 3,

1Departamento de Fisiología y Desarrollo Celular, Instituto Nacional de Perinatología, Montes Urales 800, Col. Lomas Virreyes, Deleg. Miguel Hidalgo, C.P. 11000, Ciudad de México, México

2Departamento de Fisiología. Facultad de medicina. Universidad Nacional Autónoma de México. Ciudad de México, México

3Sección de estudios de posgrado e investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis and Salvador Díaz Mirón, Ciudad de México, México

4Departamento de Inmuno-Bioquímica, Instituto Nacional de Perinatología, Montes Urales 800, Colonia Lomas Virreyes, 11000, Ciudad de México, México

Pub. Date: August 16, 2023

Cite this paper:
Jair Lozano-Cuenca, Oscar Alberto López-Canales, Ángel Miliar-García, María de los Ángeles Martínez–Godínez, Osiris Teran-Gallardo, María Cristina Paredes-Carbajal, Ruth Mery López-Mayorga, Enrique Fernando Castillo-Henkel, Héctor Flores-Herrera and Jorge Skiold López-Canales. Endothelium-Dependent Vasorelaxant Effect of a Bioactive Tripeptide, Valine-Proline-Proline, on Rat Aortic Rings. Journal of Food and Nutrition Research. 2023; 11(8):519-524. doi: 10.12691/jfnr-11-8-1

Abstract

The aim of this study was to gain further insights into the mechanisms responsible for the Val-Pro-Pro-induced vasodilation of rat aortic rings. The vasorelaxant effect was found at 10-9-10-4 M of the tripeptide on phenylephrine-precontracted rings. It was endothelium-dependent and concentration-dependent at the higher concentrations. The vasodilator response was not modified by preincubation with 3.1 x 10-7 M glibenclamide, 10-3 M 4-aminopyridine (4-AP), 10-5 M indomethacin or 10-5 M cycloheximide. However, this response was significantly diminished by preincubation with 10-5 M L-NG-Nitroarginine methyl ester (L-NAME), 10-7 M 1H-(1,2,4)oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), 10-6 M (9S,10R,12R)-2,3,9,10,11,12-hexahydro-10-methoxy-2,9-dimethyl-1-oxo-9,12-epoxy-1H-diindolo[1,2,3-fg:3',2',1'-kl]pyrrolo[3,4-i]benzodiazocine-10-carboxylic acid, methyl ester (KT 5823), 10-2 M tetraethylammonium (TEA) and 10-7 M apamin plus 10-7 M charybdotoxin, as well as by the removal of the vascular endothelium. Apparently, Val-Pro-Pro directly produced vasorelaxation of phenylephrine-precontracted rat aortic rings by stimulating the vascular endothelium and activating the NO/cGMP/PKG/Ca2+-activated K+ channel pathway.

Keywords:
bioactive peptides nitric oxide potassium channels rat aorta vascular endothelium.

Creative CommonsThis work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

References:

[1]  World Health Organization. A global brief on Hypertension: silent killer, global public health crises (World Health Day 2013). Geneva: WHO 2013. [Online]
 
[2]  Ozemek C, Tiwari SC, Sabbahi A, Carbone S, Lavie CJ. Impact of therapeutic lifestyle changes in resistant hypertension. Prog Cardiovasc Dis. 2019; S0033-0620(19)30146-X. doi:10.1016/j.pcad.2019.11.012.
 
[3]  Carey, V.J.; Bishop, L.; Charleston, J.; Conlin, P.; Erlinger, T.; Laranjo, N.; McCarron, P.; Miller, E.; Rosner, B.; Swain, J.; et al. Rationale and Design of the Optimal Macro-Nutrient Intake Heart Trial to Prevent Heart Disease (OMNI-Heart). Clin. Trials 2005, 2, 529–37.
 
[4]  Hartmann, R.; Meisel, H. Food-Derived Peptides with Biological Activity: From Research to Food Applications. Curr. Opin. Biotechnol. 2007, 18, 163–69.
 
[5]  Nakamura Y, Yamamoto N, Sakai K, Okubo A, Yamazaki S, Takano T. Purification and characterization of angiotensin I-converting enzyme inhibitors from sour milk. J Dairy Sci 1995; 78: 777–83.
 
[6]  Hirota T, Nonaka A, Matsushita A, Uchida N, Ohki K, Asakura M, Kitakaze M. Milk casein-derived tripeptides, VPP and IPP induced NO production in cultured endotelial cells and endothelium-dependent relaxation of isolated aortic rings. Heart Vessels 2011; 26: 549–56.
 
[7]  Hirota Tatsuhiko, Nonaka Atsuko, Matsushita Akiko, Uchida Naoto, Ohki Kohji, Asakura Masanori, Kitakaze Masafumi. Milk casein-derived tripeptides, VPP and IPP induced NO production in cultured endothelial cells and endothelium-dependent relaxation of isolated aortic rings. Heart Vessels (2011) 26: 549–56 DOI 10.1007/s00380-010-0096-y.
 
[8]  Steel RGD, Torrie JH. Principles and procedures of statistic: a biomedical approach.: McGraw-Hill, NY.; 1997.
 
[9]  Taveira G.B.; Carvalho A.O.; Rodrigues R.; Trindade F.G.; Da Cunha M.; Gomes V.M. Thionin-like peptide from Capsicum annuum fruits: Mechanism of action and synergism with fluconazole against Candida species. BMC Microbiol. 2016, 16: 12.
 
[10]  Sousa D.A.; Porto W.F.; Silva M.Z.; da Silva T.R.; Franco O.L. Influence of cysteine and tryptophan substitution on DNA-binding activity on maize α-hairpinin antimicrobial peptide. Molecules 2016, 21, 1062.
 
[11]  Huang S.-L.; Jao C.-L.; Ho K.-P.; Hsu K.-C. Dipeptidyl-peptidase IV inhibitory activity of peptides derived from tuna cooking juice hydrolysates. Peptides 2012, 35, 114–21.
 
[12]  Li-Chan E.C.; Hunag S.-L.; Jao C.-L.; Ho K.-P.; Hsu K.-C. Peptides derived from atlantic salmon skin gelatin as dipeptidyl-peptidase IV inhibitors. J. Agric. Food Chem. 2012, 60, 973–78.
 
[13]  Xiao M.; Ding L.; Yang W.; Chai L.; Sun Y.; Yang X.; Li D.; Zhang H.; Li W.; Cao Z. St20, a new venomous animal derived natural peptide with immunosuppressive and anti-inflammatory activities. Toxicon 2017, 127, 37–43.
 
[14]  Hou, H.; Fan, Y.; Wang, S.; Si, L.; Li, B. Immunomodulatory activity of Alaska pollock hydrolysates obtained by glutamic acid biosensor—Artificial neural network and the identification of its active central fragment. J. Funct. Foods 2016, 24: 37–47.
 
[15]  Xu, X.; Gao, Y. Purification and identification of angiotensin I-converting enzyme-inhibitory peptides from apalbumin 2 during simulated gastrointestinal digestion. J. Sci. Food Agric. 2015, 95, 906–14.
 
[16]  Castellano, P.; Aristoy, M.-C.; Sentandreu, M.Á.; Vignolo, G.; Toldrá, F. Peptides with angiotensin I converting enzyme (ACE) inhibitory activity generated from porcine skeletal muscle proteins by the action of meat-borne lactobacillus. J. Proteom. 2013, 89, 183–90.
 
[17]  Nakamura Y, Yamamoto N, Sakai K, Takano T.J. Antihypertensive effect of sour milk and peptides isolated from it that are inhibitors to angiotensin I-converting enzyme. Dairy Sci. 1995, 78(6):1253-57. doi: 10.3168/jds.S0022-0302(95)76745-5.
 
[18]  Zheng, Y.; Li, Y.; Zhang, Y.; Ruan, X.; Zhang, R. Purification, characterization, synthesis, in vitro ACE inhibition and in vivo antihypertensive activity of bioactive peptides derived from oil palm kernel glutelin-2 hydrolysates. J. Funct. Foods 2017, 28, 48–58.
 
[19]  Lopez J, Mendoza R, Cleva Villanueva G, Martinez G, Castillo EF, Castillo C. Participation of K+ channels in the endothelium-dependent and endothelium-independent components of the relaxant effect of rosuvastatin in rat aortic rings. J. Cardiovasc. Pharmacol. Ther. 2008; 13: 207–13.
 
[20]  Anozie O, Ross R, Oyekan AO, Yakubu MA. Differential modulation of bradykinin-induced relaxation of endothelin-1 and phenylephrine contractions of rat aorta by antioxidants. Acta Pharmacol Sin. 2007 28(10):1566-72. doi: 10.1111/j.1745-7254.2007.00631.x.
 
[21]  Palacios M, Knowles RG, Palmer RM, Moncada S. Nitric oxide from L-arginine stimulates the soluble guanylate cyclase in adrenal glands. Biochem. Biophys. Res. Commun. (1989) 165: 802-09.
 
[22]  Abderrahmane A, Salvail D, Dumoulin M, Garon J, Cadieux A, Rousseau E (1998) Direct activation of K(Ca) channel in airway smooth muscle by nitric oxide: involvement of a nitrothiosylation mechanism?. Am. J. Respir. Cell Mol. Biol. 19: 485-97.
 
[23]  Mathie A, Wooltorton JR, Watkins CS. Voltage-activated potassium channels in mammalian neurons and their block by novel pharmacological agents. Gen. Pharmacol. 1998, 30: 13-24
 
[24]  Zografos P, Li JH, Kau ST (1992) Comparison of the in vitro effects of K+ channel modulators on detrusor and portal vein strips from guinea pigs. Pharmacology 45: 216-30.
 
[25]  Ishii TM, Maylie J, Adelman JP. Determinants of apamin and d-tubocurarine block in SK potassium channels. J. Biol. Chem. 1997, 272: 23195-00.
 
[26]  Yamaguchi N, Kawaguchi K, Yamamoto N (2009) Study of the mechanism of antihypertensive peptides VPP and IPP in spontaneously hypertensive rats by DNA microarray analysis. Eur J Pharmacol 620(1–3):71–77
 
[27]  Qiu Y, Quilley J. Apamin/charybdotoxin-sensitive endothelial K+ channels contribute to acetylcholine-induced, NO-dependent vasorelaxation of rat aorta. Med Sci Monit. 2001;7(6):1129-36.
 
[28]  Corriu C, Feletou M, Canet E, Vanhoutte PM (1996) Endothelium-derived factors and hyperpolarization of the carotid artery of the guinea-pig. Br. J. Pharmacol. 119: 959-64.
 
[29]  Tottrup A, Kraglund K. Endothelium-dependent responses in small human mesenteric arteries. Physiological research / Academia Scientiarum Bohemoslovaca. (2004) 53: 255-263.
 
[30]  Moncada S, Higgs EA, Palmer RM. Characterization and biological significance of endothelium-derived relaxing factor. Biochem. Soc. Trans. (1988a) 16: 484-86.
 
[31]  Moncada S, Palmer RM, Higgs EA. The discovery of nitric oxide as the endogenous nitrovasodilator. Hypertension (1988b) 12: 365-72.
 
[32]  Moncada S, Radomski MW, Palmer RM. Endothelium-derived relaxing factor. Identification as nitric oxide and role in the control of vascular tone and platelet function. Biochem. Pharmacol. (1988c) 37: 2495-01.
 
[33]  Leblanc N, Wan X, Leung PM. Physiological role of Ca(2+)-activated and voltage-dependent K+ currents in rabbit coronary myocytes. Am. J. Physiol. 1994, 266: C1523-37.
 
[34]  Knot HJ, Nelson MT. Regulation of membrane potential and diameter by voltage-dependent K+ channels in rabbit myogenic cerebral arteries. Am. J. Physiol. 1995, 269: H348-55.
 
[35]  Nelson MT, Quayle JM (1995) Physiological roles and properties of potassium channels in arterial smooth muscle. Am. J. Physiol. 268: C799-22.
 
[36]  Yamada Yuko , Iwasaki Masashi, Usui Hachiro, Ohinata Kousaku, Marczak Ewa D, Lipkowski Andrzej W, Yoshikawa Masaaki. Rapakinin, an anti-hypertensive peptide derived from rapeseed protein, dilates mesenteric artery of spontaneously hypertensive rats via the prostaglandin IP receptor followed by CCK(1) receptor. Peptides. 2010, 31(5):909-14. doi: 10.1016/j.peptides.2010.02.013. Epub 2010 Feb 25.
 
[37]  Shobako Naohisa, Ishikado Atsushi , Ogawa Yutaro , Sono Yoko, Kusakari Takashi , Suwa Makoto, Matsumoto Motonobu , Ohinata Kousaku. Vasorelaxant and Antihypertensive Effects That Are Dependent on the Endothelial NO System Exhibited by Rice Bran-Derived Tripeptide. J Agric Food Chem. 2019, 67(5):1437-42. doi: 10.1021/acs.jafc.8b06341. Epub 2019 Jan 28.