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

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T1 - Endothelin-1 Reduces Microvascular Fluid Permeability through Secondary Release of Prostacyclin in Cat Skeletal Muscle.

AU - Bentzer, Peter

AU - Holbeck, Staffan

AU - Grände, Per-Olof

PY - 2002

Y1 - 2002

N2 - 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.

AB - 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.

KW - Epoprostenol : antagonists & inhibitors : metabolism

KW - Male

KW - Microcirculation : metabolism

KW - Muscle Skeletal : cytology : metabolism

KW - Receptors Endothelin metabolism

KW - Support Non-U.S. Gov't

KW - Tranylcypromine : pharmacology

KW - Time Factors

KW - Endothelin-1 : biosynthesis

KW - Dose-Response Relationship Drug

KW - Cats

KW - Capillary Permeability

KW - Arteries : metabolism

KW - Capillaries : metabolism

KW - Animal

U2 - 10.1006/mvre.2001.2365

DO - 10.1006/mvre.2001.2365

M3 - Article

VL - 63

SP - 50

EP - 60

JO - Microvascular Research

T2 - Microvascular Research

JF - Microvascular Research

SN - 1095-9319

IS - 1

ER -