Vascular effects of egg white-derived peptides in resistance arteries from rats. Structure-activity relationships.
BACKGROUND
The vasodilator properties of several peptide sequences derived from egg white proteins were screened in mesenteric resistance arteries from Wistar-Kyoto rats. For this, third-order branches of the mesenteric arteries from 6-month-old male rats were used. The vasodilator responses, with or without endothelium, to several peptides (0.1 mmol L(-1)) were analysed in an isometric myograph. Moreover, the effect of nitric oxide (NO) synthase (L-NAME, 100 micromol L(-1)) and cyclooxygenase (indomethacin, 10 micromol L(-1)) inhibitors on the vasodilator response was tested.


RESULTS
The peptides Arg-Ala-Asp-His-Pro-Phe-Leu, Arg-Ala-Asp-His-Pro-Phe, Arg-Ala-Asp-His-Pro, Tyr-Arg-Gly-Gly-Leu-Glu-Pro-Ile-Asn-Phe, Arg-Asp-Ile-Leu-Asn-Gln and Val-Pro-Pro showed a high endothelium-dependent vasorelaxation, whereas Phe-Arg-Ala-Asp-His-Pro-Phe-Leu was only partially endothelium-dependent. The relaxation induced by Arg-Ala-Asp-His-Pro-Phe-Leu, Arg-Ala-Asp-His-Pro-Phe, Arg-Ala-Asp-His-Pro, Arg-Asp-Ile-Leu-Asn-Gln and Val-Pro-Pro was mainly mediated by NO, since the response was inhibited only by L-NAME, while both L-NAME and indomethacin inhibited the vasodilator response induced by Phe-Arg-Ala-Asp-His-Pro-Phe-Leu and Tyr-Arg-Gly-Gly-Leu-Glu-Pro-Ile-Asn-Phe. The presence of Arg or Tyr at the N-terminal position could be related to the vasodilator activity of these compounds in this vascular bed. The well-known angiotensin-converting enzyme inhibitor captopril showed only a slight vasodilator effect.


CONCLUSIONS
These peptides could reduce the vascular resistance and be used as functional ingredients in the prevention and/or treatment of hypertension and other associated disorders.
Garcia-Redondo
Ana B
AB
Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain.
Roque
Fernanda R
FR
Miguel
Marta
M
López-Fandiño
Rosina
R
Salaices
Mercedes
M
D000595:Amino Acid Sequence; D000818:Animals; D002216:Captopril / Q000494:pharmacology; D004527:Egg Proteins / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D014655:Vascular Resistance / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D004527:Egg Proteins; D004791:Enzyme Inhibitors; D010455:Peptides; D014665:Vasodilator Agents; D009569:Nitric Oxide; D002216:Captopril; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin