Advanced

Endothelium-dependent relaxation by substance P in human isolated omental arteries and veins: relative contribution of prostanoids, nitric oxide and hyperpolarization

Wallerstedt, Susanna M and Bodelsson, Mikael LU (1997) In British Journal of Pharmacology 120(1). p.25-30
Abstract
1. The objective of the present study was to investigate human omental arteries and veins with respect to: (i) the contractile effect of the thromboxane A2 analogue U46619, (ii) endothelium-dependency and mediators of the relaxing effect of substance P (SP) and acetylcholine (ACh). 2. Changes in isometric tension in response to administration of U46619, SP and ACh were measured in human isolated omental arteries and veins with and without endothelium. To investigate the mechanism of action of SP, the SP-induced relaxation was measured in the presence of indomethacin (cyclo-oxygenase inhibitor), NG-monomethyl-L-arginine (L-NMMA, nitric oxide-synthase inhibitor), KCl (inhibitor of endothelium-dependent hyperpolarization), tetraethylammonium... (More)
1. The objective of the present study was to investigate human omental arteries and veins with respect to: (i) the contractile effect of the thromboxane A2 analogue U46619, (ii) endothelium-dependency and mediators of the relaxing effect of substance P (SP) and acetylcholine (ACh). 2. Changes in isometric tension in response to administration of U46619, SP and ACh were measured in human isolated omental arteries and veins with and without endothelium. To investigate the mechanism of action of SP, the SP-induced relaxation was measured in the presence of indomethacin (cyclo-oxygenase inhibitor), NG-monomethyl-L-arginine (L-NMMA, nitric oxide-synthase inhibitor), KCl (inhibitor of endothelium-dependent hyperpolarization), tetraethylammonium (TEA; non-selective inhibitor of K(+)-channels, with some preference for the high conductance Ca(2+)-activated K(+)-channel, BKCa), glibenclamide (inhibitor of the ATP-sensitive K(+)-channel) and/or clotrimazole (inhibitor of the cytochrome P450-system and the intermediate conductance Ca(2+)-activated K(+)-channel, IKCa). 3. U46619 contracted both the artery and the vein segments. Endothelium removal did not alter the contraction. 4. ACh caused neither contraction nor relaxation in artery and vein segments precontracted with U46619. 5. In both artery and vein segments precontracted with U46619, SP produced endothelium-dependent relaxation. The relaxation was unaffected by indomethacin, but was incompletely reduced by L-NMMA and KCl respectively. The L-NMMA-resistent relaxation was abolished in the presence of KCl. 6. TEA inhibited the SP-induced relaxation in artery and vein segments both in the presence and absence of L-NMMA and indomethacin, while glibenclamide and clotrimazole had no effect. 7. In conclusion, the SP-induced relaxation in human omental arteries and veins seems to be mediated via NO and endothelium-dependent hyperpolarization. KATP and IKCa are probably not involved in the hyperpolarization, but activation of BKCa may contribute to the hyperpolarization. Prostanoid synthesis and the cytochrome P450-system are probably not involved in the SP-induced relaxation in this area. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Human blood vessels, substance P, nitric oxide, hyperpolarization, K+ channels
in
British Journal of Pharmacology
volume
120
issue
1
pages
25 - 30
publisher
The British Pharmacological Society
external identifiers
  • pmid:9117094
  • scopus:0031037450
ISSN
1476-5381
DOI
10.1038/sj.bjp.0700879
language
English
LU publication?
yes
id
af0af704-760f-4ef6-90a7-5721fd37da2c (old id 1111526)
date added to LUP
2008-07-17 15:43:32
date last changed
2017-07-30 04:25:22
@article{af0af704-760f-4ef6-90a7-5721fd37da2c,
  abstract     = {1. The objective of the present study was to investigate human omental arteries and veins with respect to: (i) the contractile effect of the thromboxane A2 analogue U46619, (ii) endothelium-dependency and mediators of the relaxing effect of substance P (SP) and acetylcholine (ACh). 2. Changes in isometric tension in response to administration of U46619, SP and ACh were measured in human isolated omental arteries and veins with and without endothelium. To investigate the mechanism of action of SP, the SP-induced relaxation was measured in the presence of indomethacin (cyclo-oxygenase inhibitor), NG-monomethyl-L-arginine (L-NMMA, nitric oxide-synthase inhibitor), KCl (inhibitor of endothelium-dependent hyperpolarization), tetraethylammonium (TEA; non-selective inhibitor of K(+)-channels, with some preference for the high conductance Ca(2+)-activated K(+)-channel, BKCa), glibenclamide (inhibitor of the ATP-sensitive K(+)-channel) and/or clotrimazole (inhibitor of the cytochrome P450-system and the intermediate conductance Ca(2+)-activated K(+)-channel, IKCa). 3. U46619 contracted both the artery and the vein segments. Endothelium removal did not alter the contraction. 4. ACh caused neither contraction nor relaxation in artery and vein segments precontracted with U46619. 5. In both artery and vein segments precontracted with U46619, SP produced endothelium-dependent relaxation. The relaxation was unaffected by indomethacin, but was incompletely reduced by L-NMMA and KCl respectively. The L-NMMA-resistent relaxation was abolished in the presence of KCl. 6. TEA inhibited the SP-induced relaxation in artery and vein segments both in the presence and absence of L-NMMA and indomethacin, while glibenclamide and clotrimazole had no effect. 7. In conclusion, the SP-induced relaxation in human omental arteries and veins seems to be mediated via NO and endothelium-dependent hyperpolarization. KATP and IKCa are probably not involved in the hyperpolarization, but activation of BKCa may contribute to the hyperpolarization. Prostanoid synthesis and the cytochrome P450-system are probably not involved in the SP-induced relaxation in this area.},
  author       = {Wallerstedt, Susanna M and Bodelsson, Mikael},
  issn         = {1476-5381},
  keyword      = {Human blood vessels,substance P,nitric oxide,hyperpolarization,K+ channels},
  language     = {eng},
  number       = {1},
  pages        = {25--30},
  publisher    = {The British Pharmacological Society},
  series       = {British Journal of Pharmacology},
  title        = {Endothelium-dependent relaxation by substance P in human isolated omental arteries and veins: relative contribution of prostanoids, nitric oxide and hyperpolarization},
  url          = {http://dx.doi.org/10.1038/sj.bjp.0700879},
  volume       = {120},
  year         = {1997},
}