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

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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 < 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.

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Subject classification (UKÄ) – MANDATORY

  • Basic Medicine

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
Original languageEnglish
Pages (from-to)50-60
JournalMicrovascular Research
Volume63
Issue number1
Publication statusPublished - 2002
Publication categoryResearch
Peer-reviewedYes