PREVENTION OF CYCLOSPORINE-A-INDUCED VASCULAR TOXICITY BY PENTOXIFYLLINE

被引:25
作者
BERKENBOOM, G
UNGER, P
GOLDMAN, M
FANG, ZY
FONTAINE, J
机构
[1] UNIV LIBRE BRUXELLES, INST PHARM, DEPT PHARMACOL, B-1050 BRUSSELS, BELGIUM
[2] ERASME UNIV HOSP, DEPT IMMUNOL, B-1070 BRUSSELS, BELGIUM
关键词
CYCLOSPORINE-A; PENTOXIFYLLINE; RAT AORTA;
D O I
10.1097/00005344-199111000-00015
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
To determine whether an in vivo treatment with pentoxifylline (PTX) can prevent the vascular toxicity of cyclosporine A (Cx), three groups of rats were studied in parallel. The first group received daily injections of Cx (20 mg/kg intramuscularly) and pentoxifylline (80 mg/kg intraperitoneally) for 7 days, the second group was treated with Cx only, and the third group served as control (vehicle treatment). Cx serum levels were similar in groups 1 and 2. In thoracic aortic rings isolated from Cx group (group 2), the concentration-response curves to phenylephrine were potentiated: there was a significant leftward shift (p < 0.001 vs. control) in the EC50 values and an increase in the maximal responses (p < 0.05). After mechanical removal of the endothelium or inhibition of endothelium-derived relaxing factor formation (incubation with N(G)-monomethyl-L-arginine, L-NMMA), this enhanced responsiveness to phenylephrine persisted. In preparations from the same group (group 2), the endothelium-dependent relaxations to acetylcholine (ACh) were decreased whereas the endothelium-independent relaxations to nitroprusside (NTP 0.01-10 nM) and forskolin (1 nM) were slightly attenuated but without changes in the maximal response. In the group cotreated with Cx and PTX (group 1), the responses to ACh, NTP, and forskolin were not different from controls whereas the greater responsiveness to phenylephrine was only partially attenuated. In vivo cotreatment with PTX may prevent the endothelial dysfunction and the functional changes in smooth muscle cells induced by Cx.
引用
收藏
页码:761 / 768
页数:8
相关论文
共 21 条
[1]   CYCLOSPORINE-ASSOCIATED HYPERTENSION [J].
BENNETT, WM ;
PORTER, GA .
AMERICAN JOURNAL OF MEDICINE, 1988, 85 (02) :131-133
[2]   ENDOTHELIUM-DEPENDENT EFFECTS OF PENTOXIFYLLINE IN RAT AORTA [J].
BERKENBOOM, G ;
FANG, ZY ;
UNGER, P ;
GOLDMAN, M ;
FONTAINE, J .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1991, 193 (01) :81-86
[3]   TROPHIC EFFECTS OF PERIPHERAL ADRENERGIC-NERVES ON VASCULAR STRUCTURE [J].
BEVAN, RD .
HYPERTENSION, 1984, 6 (06) :19-26
[4]   CYCLOSPORINE A INHIBITS ENDOTHELIUM-DEPENDENT VASODILATATION AND VASCULAR PROSTACYCLIN PRODUCTION [J].
BOSSALLER, C ;
FORSTERMANN, U ;
HERTEL, R ;
OLBRICHT, C ;
RESCHKE, V ;
FLECK, E .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1989, 165 (01) :165-169
[5]   PREVENTION OF CYCLOSPORINE-INDUCED NEPHROTOXICITY WITH PENTOXIFYLLINE [J].
BRUNNER, LJ ;
VADIEI, K ;
IYER, LV ;
LUKE, DR .
RENAL FAILURE, 1989, 11 (2-3) :97-104
[6]   CLINICAL-PHARMACOLOGY OF PENTOXIFYLLINE WITH SPECIAL REFERENCE TO ITS HEMORRHEOLOGIC EFFECT FOR THE TREATMENT OF INTERMITTENT CLAUDICATION [J].
DETTELBACH, HR ;
AVIADO, DM .
JOURNAL OF CLINICAL PHARMACOLOGY, 1985, 25 (01) :8-26
[7]   THE OBLIGATORY ROLE OF ENDOTHELIAL-CELLS IN THE RELAXATION OF ARTERIAL SMOOTH-MUSCLE BY ACETYLCHOLINE [J].
FURCHGOTT, RF ;
ZAWADZKI, JV .
NATURE, 1980, 288 (5789) :373-376
[8]  
GRIEPP RB, 1977, SURGERY, V81, P262
[9]   THE PHARMACOLOGICAL AND PHYSIOLOGICAL-ROLE OF CYCLIC-GMP IN VASCULAR SMOOTH-MUSCLE RELAXATION [J].
IGNARRO, LJ ;
KADOWITZ, PJ .
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, 1985, 25 :171-191
[10]   CYCLOSPORINE AUGMENTS REACTIVITY OF ISOLATED BLOOD-VESSELS [J].
LAMB, FS ;
WEBB, RC .
LIFE SCIENCES, 1987, 40 (26) :2571-2578