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P2Y receptor-induced EDHF vasodilatation is of primary importance for the regulation of perfusion pressure in the peripheral circulation of the rat.

Malmsjö, Malin LU ; Chu, Z M; Croft, K; Erlinge, David LU ; Edvinsson, Lars LU and Beilin, L J (2002) In Acta Physiologica Scandinavica1888-12-31+01:002006-01-01+01:00 174(4). p.301-309
Abstract
Extracellular nucleotides have been shown to induce vasodilatation of conductance arteries by release of the endothelium-derived hyperpolarizing factor (EDHF). As small resistance arteries are of greater importance for blood pressure regulation, a whole rat mesenteric arterial bed preparation was used in the present study when evaluating the physiological relevance for EDHF in mediating nucleotide dilatation. Dilatory responses were examined after pre-contraction with noradrenaline in the presence of 10 mM indomethacin. Adenosine-5'-O-thiodiphosphate (ADPbetaS), adenosine triphosphate (ATP) and uridine triphosphate (UTP) induced vasodilatation (pEC50=6.5-7 and E(max)=40-70%), while uridine diphosphate (UDP) was ineffective.... (More)
Extracellular nucleotides have been shown to induce vasodilatation of conductance arteries by release of the endothelium-derived hyperpolarizing factor (EDHF). As small resistance arteries are of greater importance for blood pressure regulation, a whole rat mesenteric arterial bed preparation was used in the present study when evaluating the physiological relevance for EDHF in mediating nucleotide dilatation. Dilatory responses were examined after pre-contraction with noradrenaline in the presence of 10 mM indomethacin. Adenosine-5'-O-thiodiphosphate (ADPbetaS), adenosine triphosphate (ATP) and uridine triphosphate (UTP) induced vasodilatation (pEC50=6.5-7 and E(max)=40-70%), while uridine diphosphate (UDP) was ineffective. Endothelium-derived hyperpolarizing factor was studied in the presence of 0.5 mM Nvarpi-nitro-L-arginine (L-NOARG). ADPbetaS and UTP induced strong and potent EDHF-dilatations, while ATP only had a weak effect (E(max)=25%). After P2X1 receptor desensitization with 10 microM alphabeta-methylene-adenosine triphosphate, the ATP response was significantly increased (E(max)=65%). Putatively, this could be because of simultaneous activation of both endothelial P2Y receptors and P2X1 receptors on smooth muscle cells, which resulted in the release of EDHF and subsequent hyperpolarization, and depolarization, respectively. Nitric oxide (NO) was studied in the presence of 60 mM K+. ADPbetaS, ATP and UTP induced weak NO dilatations, suggesting a minor role for NO as compared with EDHF. In conclusion, extracellular nucleotides stimulate dilatation by activating P2Y(1) and P2Y(2)/P2Y(4) receptors, but not P2Y(6) receptors. The dilatory responses are mediated primarily by EDHF in the peripheral vascular bed. (Less)
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publication status
published
subject
keywords
Vascular : drug effects, Vasodilator Agents : pharmacology, Vasodilation : drug effects, Non-U.S. Gov't, Support, Splanchnic Circulation : physiology, Splanchnic Circulation : drug effects, Purinergic P2 : physiology, Receptors, Sprague-Dawley, Rats, Mesenteric Arteries : drug effects, Mesenteric Arteries : physiology, Drug Synergism, Endothelium, Animal, Drug, Dose-Response Relationship, Biological Factors : pharmacology, Female, Vascular : physiology
in
Acta Physiologica Scandinavica1888-12-31+01:002006-01-01+01:00
volume
174
issue
4
pages
301 - 309
publisher
Wiley-Blackwell
external identifiers
  • wos:000174851900001
  • scopus:0036268291
ISSN
0001-6772
DOI
10.1046/j.1365-201x.2002.00956.x
language
English
LU publication?
yes
id
7192757d-2d96-41fe-94d7-2daa1f7fe772 (old id 107512)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11942917&dopt=Abstract
date added to LUP
2007-06-29 14:11:40
date last changed
2017-11-27 13:21:35
@article{7192757d-2d96-41fe-94d7-2daa1f7fe772,
  abstract     = {Extracellular nucleotides have been shown to induce vasodilatation of conductance arteries by release of the endothelium-derived hyperpolarizing factor (EDHF). As small resistance arteries are of greater importance for blood pressure regulation, a whole rat mesenteric arterial bed preparation was used in the present study when evaluating the physiological relevance for EDHF in mediating nucleotide dilatation. Dilatory responses were examined after pre-contraction with noradrenaline in the presence of 10 mM indomethacin. Adenosine-5'-O-thiodiphosphate (ADPbetaS), adenosine triphosphate (ATP) and uridine triphosphate (UTP) induced vasodilatation (pEC50=6.5-7 and E(max)=40-70%), while uridine diphosphate (UDP) was ineffective. Endothelium-derived hyperpolarizing factor was studied in the presence of 0.5 mM Nvarpi-nitro-L-arginine (L-NOARG). ADPbetaS and UTP induced strong and potent EDHF-dilatations, while ATP only had a weak effect (E(max)=25%). After P2X1 receptor desensitization with 10 microM alphabeta-methylene-adenosine triphosphate, the ATP response was significantly increased (E(max)=65%). Putatively, this could be because of simultaneous activation of both endothelial P2Y receptors and P2X1 receptors on smooth muscle cells, which resulted in the release of EDHF and subsequent hyperpolarization, and depolarization, respectively. Nitric oxide (NO) was studied in the presence of 60 mM K+. ADPbetaS, ATP and UTP induced weak NO dilatations, suggesting a minor role for NO as compared with EDHF. In conclusion, extracellular nucleotides stimulate dilatation by activating P2Y(1) and P2Y(2)/P2Y(4) receptors, but not P2Y(6) receptors. The dilatory responses are mediated primarily by EDHF in the peripheral vascular bed.},
  author       = {Malmsjö, Malin and Chu, Z M and Croft, K and Erlinge, David and Edvinsson, Lars and Beilin, L J},
  issn         = {0001-6772},
  keyword      = {Vascular : drug effects,Vasodilator Agents : pharmacology,Vasodilation : drug effects,Non-U.S. Gov't,Support,Splanchnic Circulation : physiology,Splanchnic Circulation : drug effects,Purinergic P2 : physiology,Receptors,Sprague-Dawley,Rats,Mesenteric Arteries : drug effects,Mesenteric Arteries : physiology,Drug Synergism,Endothelium,Animal,Drug,Dose-Response Relationship,Biological Factors : pharmacology,Female,Vascular : physiology},
  language     = {eng},
  number       = {4},
  pages        = {301--309},
  publisher    = {Wiley-Blackwell},
  series       = {Acta Physiologica Scandinavica1888-12-31+01:002006-01-01+01:00},
  title        = {P2Y receptor-induced EDHF vasodilatation is of primary importance for the regulation of perfusion pressure in the peripheral circulation of the rat.},
  url          = {http://dx.doi.org/10.1046/j.1365-201x.2002.00956.x},
  volume       = {174},
  year         = {2002},
}