INTERACTIONS OF PALMITOYL CARNITINE WITH THE ENDOTHELIUM IN RAT AORTA

被引:13
作者
DAINTY, IA
BIGAUD, M
MCGRATH, JC
SPEDDING, M
机构
[1] SYNTEX RES CTR,RES PK,EDINBURGH EH14 4AP,SCOTLAND
[2] UNIV GLASGOW,INST PHYSIOL,GLASGOW G12 8QQ,SCOTLAND
[3] MERRELL DOW RES INST,RES INST,F-67084 STRASBOURG,FRANCE
关键词
D O I
10.1111/j.1476-5381.1990.tb15789.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Palmitoyl carnitine (10-1000 μM) resembled Bay K 8644 (10-1000 nM) in that it directly contracted rat aortic rings which were partially depolarized with K+ (12 mM). However, the effects of Bay K 8644 were reduced in the presence of endothelium whereas the presence of the endothelium hardly affected the palmitoyl carnitine-induced contractions, which occurred at high concentrations (>10 μM). Lower concentrations of palmitoyl carnitine (0.3-30 μM; EC50 1.1 μM), but not Bay K 8644, carnitine or palmitic acid, antagonized the relaxant effects of acetylcholine in rat aorta. The antagonism was specific for endothelium-dependent relaxations, in that the relaxations to ATP and the calcium ionophore A23187 were also non-competitively antagonized, albeit at slightly higher concentrations, whereas the direct relaxant effects of sodium nitroprusside were unaffected. Palmitoyl carnitine therefore antagonizes the effects or the release of endothelial-derived relaxant factor (EDRF). The inhibitory effects were reversed on prolonged washout, indicating that the effects were not due to destruction of the endothelial cells. In superfusion experiments, palmitoyl carnitine inhibited the release of EDRF from rat aorta but did not affect the responsiveness to exogenous EDRF; indicating a site of action at the endothelial cell. In superfusion experiments, palmitoyl carnitine inhibited the release of EDRF from rat aorta but did not effect the responsiveness to exogenous EDRF, indicating a site of action at the endothelial cell. In superfusion experiments, palmitoyl carnitine, and lysophosphatidyl choline, caused direct relaxations of the aorta, indicating EDRF release, prior to inhibition of release evoked by receptor stimulation. These substances may modulate vascular responsiveness under certain conditions.
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页码:241 / 246
页数:6
相关论文
共 30 条
[1]  
BIGAUD M, 1986, British Journal of Pharmacology, V89, p540P
[2]   EXOGENOUS PALMITOYL CARNITINE AND MEMBRANE DAMAGE IN RAT HEARTS [J].
BUSSELEN, P ;
SERCU, D ;
VERDONCK, F .
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 1988, 20 (10) :905-916
[3]   AMPHIPATHIC METABOLITES AND MEMBRANE DYSFUNCTION IN ISCHEMIC MYOCARDIUM [J].
CORR, PB ;
GROSS, RW ;
SOBEL, BE .
CIRCULATION RESEARCH, 1984, 55 (02) :135-154
[4]   ELECTRO-PHYSIOLOGICAL EFFECTS OF AMPHIPHILES ON CANINE PURKINJE-FIBERS - IMPLICATIONS FOR DYSRHYTHMIA SECONDARY TO ISCHEMIA [J].
CORR, PB ;
SNYDER, DW ;
CAIN, ME ;
CRAFFORD, WA ;
GROSS, RW ;
SOBEL, BE .
CIRCULATION RESEARCH, 1981, 49 (02) :354-363
[5]   PATHOPHYSIOLOGICAL CONCENTRATIONS OF LYSOPHOSPHATIDES AND THE SLOW RESPONSE [J].
CORR, PB ;
SNYDER, DW ;
LEE, BI ;
GROSS, RW ;
KEIM, CR ;
SOBEL, BE .
AMERICAN JOURNAL OF PHYSIOLOGY, 1982, 243 (02) :H187-H195
[6]  
CRIDDLE DN, 1987, J PHYSIOL-LONDON, V391, pP47
[7]  
DAINTY LA, 1987, BLOOD VESSELS, V24, P203
[8]  
DUNCAN G P, 1987, British Journal of Pharmacology, V92, p554P
[9]   MODULATION OF CANINE MYOCARDIAL SARCOLEMMAL MEMBRANE FLUIDITY BY AMPHIPHILIC COMPOUNDS [J].
FINK, KL ;
GROSS, RW .
CIRCULATION RESEARCH, 1984, 55 (05) :585-594
[10]   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