ENHANCEMENT BY ENDOTHELIN-1 OF MICROVASCULAR PERMEABILITY VIA THE ACTIVATION OF ET(A) RECEPTORS

被引:74
作者
FILEP, JG
SIROIS, MG
FOLDESFILEP, E
ROUSSEAU, A
PLANTE, GE
FOURNIER, A
YANO, M
SIROIS, P
机构
[1] UNIV SHERBROOKE,FAC MED,DEPT PHARMACOL,SHERBROOKE J1H 5N4,QUEBEC,CANADA
[2] NATL RECH SCI SANTE,MONTREAL H9R 1G6,PQ,CANADA
[3] BANYU PHARMACEUT CO,CENT RES LABS,TSUKUBA,JAPAN
关键词
ENDOTHELIN-1; ET(A) RECEPTOR; PROTEIN EXTRAVASATION; HEMOCONCENTRATION; AIRWAYS; GASTROINTESTINAL TRACT; KIDNEY; BQ-123;
D O I
10.1111/j.1476-5381.1993.tb13657.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
1 The objective of the present experiments was to assess the involvement of endothelin-A (ET(A)) receptors in mediating the effects of endothelin-1 on microvascular permeability in conscious rats. 2 Bolus injection of endothelin- 1 (0. 1 and 1 nmol kg-1, i.v.) resulted in a dose-dependent prolonged pressor effect preceded by a transient depressor response. These changes were accompanied by a dose-dependent loss of plasma volume. Endothelin- 1 (I nmol kg-1) enhanced the vascular permeability of the upper and lower bronchi, kidney, stomach, duodenum and spleen (up to 270%) as measured by the extravasation of Evans blue dye. 3 Pretreatment of the animals with the selective ET(A) receptor antagonist, BQ-123 (1 mg kg-1, i.v.) significantly blunted the pressor response to endothelin-I without affecting the depressor response. BQ-123 inhibited by 87% the endothelin-I (I nmol kg-1)-induced plasma volume loss. BQ-123 markedly attenuated protein extravasation elicited by endothelin-I in the upper and lower bronchi and kidney, whereas it completely inhibited the permeability effect of endothelin-1 in the stomach and duodenum. BQ-123 by itself had no significant effect on the parameters studied. 4 The endothelin-I analogue, [Trp(For)21]-endothelin-1, in which Trp21 is formylated, was as potent a pressor agent as endothelin-1, but had no depressor action. Bolus injection of [Trp(For)21]-endothelin-I (0.1 and 1 nmol kg-1, i.v.) evoked similar plasma volume losses to those observed following administration of equimolar doses of endothelin-1. Furthermore, 1 nmol kg-1 [Trp(For)21]-endothelin-I evoked increases in protein extravasation similar to endothelin- 1, 1 nmol kg-1. 5 The present findings suggest that endothelin-I enhances microvascular permeability, in part, via the activation of ET(A) receptors.
引用
收藏
页码:880 / 886
页数:7
相关论文
共 33 条
  • [1] INTERACTIONS AMONG INFLAMMATORY MEDIATORS ON EDEMA FORMATION IN THE CANINE FORELIMB
    AMELANG, E
    PRASAD, CM
    RAYMOND, RM
    GREGA, GJ
    [J]. CIRCULATION RESEARCH, 1981, 49 (02) : 298 - 306
  • [2] CLONING AND EXPRESSION OF A CDNA-ENCODING AN ENDOTHELIN RECEPTOR
    ARAI, H
    HORI, S
    ARAMORI, I
    OHKUBO, H
    NAKANISHI, S
    [J]. NATURE, 1990, 348 (6303) : 730 - 732
  • [3] ENDOTHELIN INDUCES POTENT MICROVASCULAR CONSTRICTION
    BRAIN, SD
    TIPPINS, JR
    WILLIAMS, TJ
    [J]. BRITISH JOURNAL OF PHARMACOLOGY, 1988, 95 (04) : 1005 - 1007
  • [4] ENDOTHELIN-1 - DEMONSTRATION OF POTENT EFFECTS ON THE MICROCIRCULATION OF HUMANS AND OTHER SPECIES
    BRAIN, SD
    CROSSMAN, DC
    BUCKLEY, TL
    WILLIAMS, TJ
    [J]. JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, 1989, 13 : S147 - S150
  • [5] ANTI-INFLAMMATORY EFFECTS OF ENDOTHELIN-1
    CHANDER, CL
    MOORE, AR
    DESA, FM
    HOWAT, DW
    WILLOUGHBY, DA
    [J]. JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, 1989, 13 : S218 - S219
  • [6] REGIONAL HEMODYNAMIC-EFFECTS OF ENDOTHELIN-1 IN RAT AND MAN - UNEXPECTED ADVERSE REACTIONS
    DAHLOF, B
    GUSTAFSSON, D
    HEDNER, T
    JERN, S
    HANSSON, L
    [J]. JOURNAL OF HYPERTENSION, 1990, 8 (09) : 811 - 817
  • [7] ENDOTHELIUM-DEPENDENT MESENTERIC VASORELAXANT EFFECTS AND SYSTEMIC ACTIONS OF ENDOTHELIN (16-21) AND OTHER ENDOTHELIN-RELATED PEPTIDES IN THE RAT
    DOUGLAS, SA
    HILEY, CR
    [J]. BRITISH JOURNAL OF PHARMACOLOGY, 1991, 104 (02) : 311 - 320
  • [8] RESPONSES TO ENDOTHELIN-1, HUMAN PROENDOTHELIN (1-38) AND PORCINE PROENDOTHELIN (1-39) IN THE RAT ON INTRAVENOUS ADMINISTRATION AND IN THE BLOOD PERFUSED MESENTERY
    DOUGLAS, SA
    HILEY, CR
    [J]. NEUROCHEMISTRY INTERNATIONAL, 1991, 18 (04) : 445 - 454
  • [9] MULTIPLE COMPARISONS USING RANK SUMS
    DUNN, OJ
    [J]. TECHNOMETRICS, 1964, 6 (03) : 241 - &
  • [10] VASCULAR-RESPONSES TO LEUKOTRIENE-B4, LEUKOTRIENE-C4 AND LEUKOTRIENE-D4 FOLLOWING FPL 55712, INDOMETHACIN, SARALASIN, PHENTOLAMINE AND VERAPAMIL IN THE CONSCIOUS RAT
    FILEP, J
    FOLDESFILEP, E
    FROLICH, JC
    [J]. BRITISH JOURNAL OF PHARMACOLOGY, 1987, 90 (02) : 431 - 439