PULSE EXPOSURE TO PROTEIN-SYNTHESIS INHIBITORS ENHANCES VASCULAR-RESPONSES TO DES-ARG9-BRADYKININ - POSSIBLE ROLE OF INTERLEUKIN-1

被引:87
作者
DEBLOIS, D [1 ]
BOUTHILLIER, J [1 ]
MARCEAU, F [1 ]
机构
[1] UNIV LAVAL,CTR RECH,HOTEL DIEU QUEBEC,11 COTE PALAIS,QUEBEC CITY G1R 2J6,QUEBEC,CANADA
关键词
DES-ARG9-BRADYKININ; BIOLOGICAL ACTIVITY; RABBIT AORTIC STRIPS; SENSITIZATION TO KININS; MODULATION; CYCLOHEXIMIDE; VASCULAR EFFECTS; INTERLEUKIN-1;
D O I
10.1111/j.1476-5381.1991.tb12300.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
1 The modulation of the spontaneous increase in contractile responses to des-Arg9-bradykinin (des-Arg9-BK) of rabbit aortic strips incubated in vitro was studied. Rapid hypotensive responses to exogenous kinins were also measured in rabbits anaesthetized 5 h following pretreatment. 2 Continuous exposure to the protein synthesis inhibitors cycloheximide (71-mu-M) or anisomycin (3.8-mu-M) profoundly inhibited the sensitization to des-Arg9-BK in incubated aortic strips. However, temporary (3 h) inhibition of protein synthesis in vitro followed by further incubation (3 h) of tissues without inhibitor, paradoxically enhanced both the maximal contractile responses to des-Arg9-BK (1.7-mu-M) and the apparent affinity of the kinin without affecting contractions to noradrenaline (NA, 100 nM) at 6.5 h. 3 The stimulatory activity of the short treatment (pulse) with cycloheximide was abolished in the presence of dexamethasone sodium phosphate (100-mu-M throughout the incubation). The function of receptors for kinins did not appear to be altered directly by the steroid treatment. 4 Interleukin-1-beta (IL-1-beta), applied at low concentrations (100-250 pg ml-1) on aortic strips between 3 h and 6.5 h of incubation time, mimicked the selective stimulatory effect of the cycloheximide pulse on responses to des-Arg9-BK. Higher concentrations of IL-1-beta (0.5-5 ng ml-1) did not further amplify the responses to des-Arg9-BK but decreased the contractile responses to NA. 5 The modulation by IL-1-beta of vascular sensitivity to des-Arg9-BK and to NA was prevented by blockade of protein synthesis. 6 The induction in vivo by IL-1-beta (5-mu-g kg-1) or by cycloheximide (10 mg kg-1) of cardiovascular responsiveness to des-Arg9-BK was demonstrated with a blood pressure assay of exogenous kinins or with tissues isolated ex vivo 5 h after pretreatment of animals. Evidence of active disposition of cycloheximide in vivo was also obtained. 7 We propose the production of endogenous IL-1 as a possible mechanism for the enhancement of responsiveness to des-Arg9-BK observed in tissues pulsed with a protein synthesis inhibitor and for the inducing effect of cycloheximide or E. coli lipopolysaccharide in vivo. These results suggest that effects mediated by the BK1 receptor for kinins are potentially present in pathological conditions associated with IL-1 production.
引用
收藏
页码:1057 / 1066
页数:10
相关论文
共 41 条
  • [1] INTERLEUKIN-1 INHIBITS CONTRACTION OF VASCULAR SMOOTH-MUSCLE
    BEASLEY, D
    COHEN, RA
    LEVINSKY, NG
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1989, 83 (01) : 331 - 335
  • [2] FURTHER EVIDENCE FOR THE EXISTENCE OF 2 RECEPTOR-SITES FOR BRADYKININ RESPONSIBLE FOR THE DIPHASIC EFFECT IN THE RAT ISOLATED DUODENUM
    BOSCHCOV, P
    PAIVA, ACM
    PAIVA, TB
    SHIMUTA, SI
    [J]. BRITISH JOURNAL OF PHARMACOLOGY, 1984, 83 (02) : 591 - 600
  • [3] STUDIES ON THE INDUCTION OF PHARMACOLOGICAL RESPONSES TO DES-ARG9-BRADYKININ INVITRO AND INVIVO
    BOUTHILLIER, J
    DEBLOIS, D
    MARCEAU, F
    [J]. BRITISH JOURNAL OF PHARMACOLOGY, 1987, 92 (02) : 257 - 264
  • [4] CANNON JG, 1989, J IMMUNOL, V142, P2299
  • [5] RELAXATION OF ISOLATED MESENTERIC-ARTERIES BY DES-ARG9-BRADYKININ STIMULATION OF B1-RECEPTORS
    CHURCHILL, L
    WARD, PE
    [J]. EUROPEAN JOURNAL OF PHARMACOLOGY, 1986, 130 (1-2) : 11 - 18
  • [6] PEPTIDES AND THE HUMAN-COLON - AN INVITRO PHARMACOLOGICAL STUDY
    COUTURE, R
    MIZRAHI, J
    REGOLI, D
    DEVROEDE, G
    [J]. CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY, 1981, 59 (09) : 957 - 964
  • [7] PHARMACOLOGICAL MODULATION OF THE UP-REGULATED RESPONSES TO DES-ARG9-BRADYKININ INVIVO AND INVITRO
    DEBLOIS, D
    BOUTHILLIER, J
    MARCEAU, F
    [J]. IMMUNOPHARMACOLOGY, 1989, 17 (03): : 187 - 198
  • [8] EFFECT OF GLUCOCORTICOIDS, MONOKINES AND GROWTH-FACTORS ON THE SPONTANEOUSLY DEVELOPING RESPONSES OF THE RABBIT ISOLATED AORTA TO DES-ARG9-BRADYKININ
    DEBLOIS, D
    BOUTHILLIER, J
    MARCEAU, F
    [J]. BRITISH JOURNAL OF PHARMACOLOGY, 1988, 93 (04) : 969 - 977
  • [9] THE ABILITY OF DES-ARG9-BRADYKININ TO RELAX RABBIT ISOLATED MESENTERIC-ARTERIES IS ACQUIRED DURING INVITRO INCUBATION
    DEBLOIS, D
    MARCEAU, F
    [J]. EUROPEAN JOURNAL OF PHARMACOLOGY, 1987, 142 (01) : 141 - 144
  • [10] MULTIPLE BIOLOGICAL-ACTIVITIES OF HUMAN RECOMBINANT INTERLEUKIN-1
    DINARELLO, CA
    CANNON, JG
    MIER, JW
    BERNHEIM, HA
    LOPRESTE, G
    LYNN, DL
    LOVE, RN
    WEBB, AC
    AURON, PE
    REUBEN, RC
    RICH, A
    WOLFF, SM
    PUTNEY, SD
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1986, 77 (06) : 1734 - 1739