Characterization of endothelium‐derived relaxing factors released by bradykinin in human resistance arteries

Relaxing factors released by the endothelium and their relative contribution to the endothelium‐dependent relaxation produced by bradykinin (BK) in comparison with different vasodilator agents were investigated in human omental resistance arteries. BK produced an endothelium‐dependent relaxation of...

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Published in:British journal of pharmacology 1997-06, Vol.121 (4), p.657-664
Main Authors: Ohlmann, P., Martínez, M. C., Schneider, F., Stoclet, J. C., Andriantsitohaina, R.
Format: Article
Language:English
Subjects:
Arteries - drug effects
Arteries - metabolism
Biological and medical sciences
Biological Factors - metabolism
Blood vessels and receptors
Bradykinin - pharmacology
Cyclooxygenase Inhibitors - pharmacology
Endothelium
Endothelium - drug effects
Endothelium, Vascular - drug effects
endothelium‐derived hyperpolarizing factor (EDHF)
Enzyme Inhibitors - pharmacology
Fundamental and applied biological sciences. Psychology
human resistance arteries
Humans
Indomethacin - pharmacology
Muscle Relaxation
NG-Nitroarginine Methyl Ester - pharmacology
Omentum - blood supply
Vertebrates: cardiovascular system
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Summary:Relaxing factors released by the endothelium and their relative contribution to the endothelium‐dependent relaxation produced by bradykinin (BK) in comparison with different vasodilator agents were investigated in human omental resistance arteries. BK produced an endothelium‐dependent relaxation of arteries pre‐contracted with the thromboxane A2 agonist, U46619. The B2 receptor antagonist, Hoe 140 (0.1, 1 and 10 μM), produced a parallel shift to the right of the concentration‐response curve to BK with a pA2 of 7.75. Neither the cyclo‐oxygenase inhibitor, indomethacin (10 μM) alone, the nitric oxide synthase inhibitor, Nω‐nitro‐L‐arginine methyl ester (L‐NAME, 300 μM) alone, the nitric oxide scavenger, oxyhaemoglobin (Hb, 10 μM) alone, nor the combination of L‐NAME plus Hb affected the concentration‐response curve to BK. Conversely, the combination of indomethacin with either L‐NAME or Hb attenuated but did not abolish the BK‐induced relaxation. By contrast, the relaxations produced by the Ca2+ ionophore, calcimycin (A23187), and by the inhibitor of sarcoplasmic reticulum Ca2+‐ATPase, thapsigargin (THAPS), were abolished in the presence of indomethacin plus L‐NAME. Also, the presence of indomethacin plus L‐NAME produced contraction of arteries with functional endothelium. The indomethacin plus L‐NAME resistant component of BK relaxation was abolished in physiological solution (PSS) containing 40 mM KCl and vice versa. However, in the presence of KCl 40 mM, indomethacin plus L‐NAME did not affect the nitric oxide donor, S‐N‐acetylpenicillamine‐induced relaxation. The indomethacin plus L‐NAME resistant component of the relaxation to BK was significantly attenuated by the K+ channel blocker tetrabutylammonium (TBA, 1 mM). However, it was not affected by other K+ channel blockers such as apamin (10 μM), 4‐aminopyridine (100 μM), glibenclamide (10 μM), tetraethylammonium (10 mM) and charybdotoxin (50 nM). In the presence of indomethacin plus L‐NAME, the relaxation produced by BK was not affected by the phospholipase A2 inhibitor, quinacrine (10 μM) or by the inhibitor of cytochrome P450, SKF 525a (10 μM). Another cytochrome P450 inhibitor, clotrimazole (10 μM) which also inhibits K+ channels, inhibited the relaxation to BK. These results show that BK induces endothelium‐dependent relaxation in human small omental arteries via multiple mechanisms involving nitric oxide, cyclo‐oxygenase derived prostanoid(s) and another factor (probably an endothelium‐derived hype
ISSN:0007-1188
1476-5381
DOI:10.1038/sj.bjp.0701169