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Vasomotor Effects Of ARG–Gly–ASP (RGD) Peptides Are Limited And Not Related To Endothelium‐Derived Hyperpolarizing Factor‐Mediated Relaxation In Rat Mesenteric Arteries
Author(s) -
Bakker Erik Ntp,
Balt Jippe C,
Pfaffendorf Martin,
Spaan Jos Ae,
VanBavel Ed
Publication year - 2001
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1046/j.1440-1681.2001.03537.x
Subject(s) - mesenteric arteries , endocrinology , medicine , endothelium derived hyperpolarizing factor , chemistry , vasomotor , vasodilation , phenylephrine , endothelium , myograph , vasoconstriction , nitric oxide , artery , charybdotoxin , blood pressure
SUMMARY 1. In the present study we tested the effect of arg–gly–asp (RGD) peptides on vasomotor responses in rat isolated mesenteric arteries. More specifically, the hypothesis was tested that RGD interaction with integrins mediates relaxation attributed to endothelium‐derived hyperpolarizing factor (EDHF). 2. The presence of the β 3 integrin subunit was shown by western blot analysis. To study its functional role, arteries (355 ± 11 μ m; n = 50) were mounted in a wire myograph set‐up to measure isometric force generation. After blockade of nitric oxide synthesis with N G ‐nitro‐ L ‐arginine (0.1 mmol/L) and prostaglandin synthesis with indomethacin (10 μ mol/L), methacholine (10 μ mol/L) induced a transient relaxation within 1 min of 72 ± 4.0% (as percentage of precontraction with phenylephrine; n = 27). 3. These responses were inhibited by a 60 mmol/L potassium buffer (18 ± 6.0%; n = 6) or endothelium denudation (12 ± 3.2%; n = 7), consistent with EDHF. 4. A function‐blocking monoclonal antibody against the integrin β 3 chain did not affect relaxation. 5. The RGD peptides gly–arg–gly–asp–thr–pro (GRGDTP), gly–arg–gly–asp–ser (GRGDS) and cyclic RGD, ligands for the RGD binding site of integrins, also did not affect relaxation induced by methacholine. 6. Cyclic RGD increased contraction from 91 ± 3 to 98 ± 3% (as percentage of 120 mmol/L potassium). 7. In conclusion, these data show that vasomotor responses related to integrins are small and not involved in hyperpolarization attributed to EDHF in rat mesenteric artery.