title: Endothelin-1 reduces microvascular fluid permeability through secondary release of prostacyclin in cat Skeletal muscle.
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, non-vasodilator 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.
authors.affiliation: Department of Physiological Sciences, University of Lund and University Hospital of Lund, Lund, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Bentzer
authors.forename: Staffan
authors.initials: S
authors.lastname: Holbeck
authors.forename: Per-Olof
authors.initials: PO
authors.lastname: Grände
mesh_terms: D000818:Animals; D001158:Arteries / Q000378:metabolism; D002196:Capillaries / Q000378:metabolism; D002199:Capillary Permeability; D002415:Cats; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000096:biosynthesis*; D011464:Epoprostenol / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D008833:Microcirculation / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism*; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000378:metabolism; D013997:Time Factors; D014191:Tranylcypromine / Q000494:pharmacology
chemical_list: D019332:Endothelin-1; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D014191:Tranylcypromine; D011464:Epoprostenol