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Endothelin-1 Reduces Microvascular Fluid Permeability through Secondary Release of Prostacyclin in Cat Skeletal Muscle.

Bentzer, Peter LU ; Holbeck, Staffan LU and Grände, Per-Olof LU (2002) In Microvascular Research 63(1). p.50-60
Abstract
The aim of the study was to analyze effects of various plasma concentrations of the vasoconstrictor endothelin-1 on microvascular fluid permeability and on transcapillary fluid exchange. We also analyzed whether the permeability-reducing substance prostacyclin is involved in the permeability effects of endothelin-1, as prostacylin is suggested to be released via ET(B) receptor stimulation. The study was performed on an autoperfused cat calf muscle preparation, and a capillary filtration coefficient (CFC) technique was used to estimate variations in microvascular fluid permeability (conductivity). Intraarterial infusion of endothelin-1 in low doses (5 and 10 ng/min/100 g muscle) caused transcapillary absorption, whereas higher doses (20-40... (More)
The aim of the study was to analyze effects of various plasma concentrations of the vasoconstrictor endothelin-1 on microvascular fluid permeability and on transcapillary fluid exchange. We also analyzed whether the permeability-reducing substance prostacyclin is involved in the permeability effects of endothelin-1, as prostacylin is suggested to be released via ET(B) receptor stimulation. The study was performed on an autoperfused cat calf muscle preparation, and a capillary filtration coefficient (CFC) technique was used to estimate variations in microvascular fluid permeability (conductivity). Intraarterial infusion of endothelin-1 in low doses (5 and 10 ng/min/100 g muscle) caused transcapillary absorption, whereas higher doses (20-40 ng/min/100 g) induced filtration despite further vasoconstriction. Low-dose endothelin-1 had no significant effect on CFC, while CFC was reduced to at most 55% of baseline at higher doses (P < 0.01). Simultaneous local intraarterial infusion of the prostacyclin synthesis inhibitor tranylcypromine restored CFC to 114% of baseline (P < 0.01) and further increased vascular resistance. A low, nonvasodilator dose of prostacyclin given intravenously counteracted the tranylcypromine effect on CFC. The decreased CFC induced by a high dose of endothelin-1 was counteracted by the ET(B) receptor antagonist BQ-788 with no change in vascular resistance (P < 0.05). We conclude that the decreased CFC following high doses of endothelin-1 can be attributed to a decrease in microvascular hydraulic conductivity, mediated by secondary release of prostacylin via stimulation of the ET(B) receptor. Endothelin-1 may induce edema through postcapillary vasoconstriction. (c)2001 Elsevier Science. (Less)
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keywords
Epoprostenol : antagonists & inhibitors : metabolism, Male, Microcirculation : metabolism, Muscle Skeletal : cytology : metabolism, Receptors Endothelin metabolism, Support Non-U.S. Gov't, Tranylcypromine : pharmacology, Time Factors, Endothelin-1 : biosynthesis, Dose-Response Relationship Drug, Cats, Capillary Permeability, Arteries : metabolism, Capillaries : metabolism, Animal
in
Microvascular Research
volume
63
issue
1
pages
50 - 60
publisher
Academic Press
external identifiers
  • wos:000173196800006
  • pmid:11749072
  • scopus:0036351269
ISSN
1095-9319
DOI
10.1006/mvre.2001.2365
language
English
LU publication?
yes
id
0915a05f-ddaf-41ee-ab49-3b9df7aeca29 (old id 106996)
alternative location
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11749072&dopt=Abstract
date added to LUP
2007-07-10 11:41:58
date last changed
2017-01-01 05:03:51
@article{0915a05f-ddaf-41ee-ab49-3b9df7aeca29,
  abstract     = {The aim of the study was to analyze effects of various plasma concentrations of the vasoconstrictor endothelin-1 on microvascular fluid permeability and on transcapillary fluid exchange. We also analyzed whether the permeability-reducing substance prostacyclin is involved in the permeability effects of endothelin-1, as prostacylin is suggested to be released via ET(B) receptor stimulation. The study was performed on an autoperfused cat calf muscle preparation, and a capillary filtration coefficient (CFC) technique was used to estimate variations in microvascular fluid permeability (conductivity). Intraarterial infusion of endothelin-1 in low doses (5 and 10 ng/min/100 g muscle) caused transcapillary absorption, whereas higher doses (20-40 ng/min/100 g) induced filtration despite further vasoconstriction. Low-dose endothelin-1 had no significant effect on CFC, while CFC was reduced to at most 55% of baseline at higher doses (P &lt; 0.01). Simultaneous local intraarterial infusion of the prostacyclin synthesis inhibitor tranylcypromine restored CFC to 114% of baseline (P &lt; 0.01) and further increased vascular resistance. A low, nonvasodilator dose of prostacyclin given intravenously counteracted the tranylcypromine effect on CFC. The decreased CFC induced by a high dose of endothelin-1 was counteracted by the ET(B) receptor antagonist BQ-788 with no change in vascular resistance (P &lt; 0.05). We conclude that the decreased CFC following high doses of endothelin-1 can be attributed to a decrease in microvascular hydraulic conductivity, mediated by secondary release of prostacylin via stimulation of the ET(B) receptor. Endothelin-1 may induce edema through postcapillary vasoconstriction. (c)2001 Elsevier Science.},
  author       = {Bentzer, Peter and Holbeck, Staffan and Grände, Per-Olof},
  issn         = {1095-9319},
  keyword      = {Epoprostenol : antagonists & inhibitors : metabolism,Male,Microcirculation : metabolism,Muscle Skeletal : cytology : metabolism,Receptors Endothelin metabolism,Support Non-U.S. Gov't,Tranylcypromine : pharmacology,Time Factors,Endothelin-1 : biosynthesis,Dose-Response Relationship Drug,Cats,Capillary Permeability,Arteries : metabolism,Capillaries : metabolism,Animal},
  language     = {eng},
  number       = {1},
  pages        = {50--60},
  publisher    = {Academic Press},
  series       = {Microvascular Research},
  title        = {Endothelin-1 Reduces Microvascular Fluid Permeability through Secondary Release of Prostacyclin in Cat Skeletal Muscle.},
  url          = {http://dx.doi.org/10.1006/mvre.2001.2365},
  volume       = {63},
  year         = {2002},
}