ROLE OF ENDOTHELIN-1 AND THE ET(A) RECEPTOR IN THE MAINTENANCE OF DEOXYCORTICOSTERONE ACETATE-SALT-INDUCED HYPERTENSION

被引:101
作者
FUJITA, K [1 ]
MATSUMURA, Y [1 ]
KITA, S [1 ]
MIYAZAKI, Y [1 ]
HISAKI, K [1 ]
TAKAOKA, M [1 ]
MORIMOTO, S [1 ]
机构
[1] OSAKA UNIV PHARMACEUT SCI,DEPT PHARMACOL,MATSUBARA,OSAKA 580,JAPAN
关键词
ENDOTHELIN-1 (ET-1); ENDOTHELIN RECEPTOR; ETA ANTAGONIST; DEOXYCORTICOSTERONE ACETATE SALT HYPERTENSION;
D O I
10.1111/j.1476-5381.1995.tb13292.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
1 To search for a possible role for endothelin-1 (ET-1) in deoxycorticosterone acetate (DOCA)-salt-induced hypertension, we examined changes in concentration of ET-I in vascular and renal tissue in DOCA-salt hypertensive rats and evaluated the antihypertensive effect of the ET(A) receptor antagonist, FR139317. 2 There was an increase in aortic immunoreactive-ET (IR-ET) concentrations in association with hypertension-induced treatment. There were no significant changes in ET-1 levels in the kidney with DOCA-salt treatment. 3 In DOCA-salt hypertensive rats, a significant correlation (r=0.83, P<0.01) was found between aortic IR-ET concentrations and systolic blood pressure. 4 High-performance liquid chromatography analysis of the aortic extract from DOCA-salt rats revealed one major component corresponding to the elution position of synthetic ET-1. 5 The intravenous bolus injection of FR139317 (10 mg kg(-1)) produced a slight decrease in blood pressure in the control rats and in the DOCA-salt hypertensive rat, FR139317 had a more pronounced hypotensive effect. 6 We propose that ET-I production in vascular tissues is increased in DOCA-salt hypertensive rats. In addition, our study indicates the pathophysiological importance of increased endogenous ET-1 in the maintenance of DOCA-salt-induced hypertension, through interaction of the peptide with ET(A) receptors.
引用
收藏
页码:925 / 930
页数:6
相关论文
共 37 条
[1]  
BAZIL MK, 1992, J CARDIOVASC PHARM, V20, P940, DOI 10.1097/00005344-199212000-00011
[2]   A SPECIFIC ENDOTHELIN SUBTYPE-A RECEPTOR ANTAGONIST PROTECTS AGAINST INJURY IN RENAL-DISEASE PROGRESSION [J].
BENIGNI, A ;
ZOJA, C ;
CORNA, D ;
ORISIO, S ;
LONGARETTI, L ;
BERTANI, T ;
REMUZZI, G .
KIDNEY INTERNATIONAL, 1993, 44 (02) :440-444
[3]   DISCRIMINATION BETWEEN ETA-RECEPTOR-MEDIATED AND ETB-RECEPTOR-MEDIATED EFFECTS OF ENDOTHELIN-1 AND [ALA1,3,11,15]ENDOTHELIN-1 BY BQ-123 IN THE ANESTHETIZED RAT [J].
BIGAUD, M ;
PELTON, JT .
BRITISH JOURNAL OF PHARMACOLOGY, 1992, 107 (04) :912-918
[4]   PATHOPHYSIOLOGICAL ROLE OF ENDOTHELIN REVEALED BY THE 1ST ORALLY-ACTIVE ENDOTHELIN RECEPTOR ANTAGONIST [J].
CLOZEL, M ;
BREU, V ;
BURRI, K ;
CASSAL, JM ;
FISCHLI, W ;
GRAY, GA ;
HIRTH, G ;
LOFFLER, BM ;
MULLER, M ;
NEIDHART, W ;
RAMUZ, H .
NATURE, 1993, 365 (6448) :759-761
[5]   IMPORTANCE OF VASOPRESSIN IN THE DEVELOPMENT AND MAINTENANCE OF DOC-SALT HYPERTENSION IN THE RAT [J].
CROFTON, JT ;
SHARE, L ;
SHADE, RE ;
LEEKWON, WJ ;
MANNING, M ;
SAWYER, WH .
HYPERTENSION, 1979, 1 (01) :31-38
[6]   PHOSPHORAMIDON-SENSITIVE CONVERSION OF BIG ENDOTHELIN-1 AND DEGRADATION OF ENDOTHELIN-1 IN RAT-KIDNEY [J].
FUJITA, K ;
MATSUMURA, Y ;
KITA, S ;
HISAKI, K ;
TAKAOKA, M ;
MORIMOTO, S .
HYPERTENSION, 1994, 24 (02) :227-233
[7]   CHARACTERIZATION OF ENDOTHELIN SECRETION BY VASCULAR ENDOTHELIAL-CELLS [J].
HEXUM, TD ;
HOEGER, C ;
RIVIER, JE ;
BAIRD, A ;
BROWN, MR .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1990, 167 (01) :294-300
[8]   ALTERATIONS IN RENAL ENDOTHELIN-1 PRODUCTION IN THE SPONTANEOUSLY HYPERTENSIVE RAT [J].
HUGHES, AK ;
CLINE, RC ;
KOHAN, DE .
HYPERTENSION, 1992, 20 (05) :666-673
[9]   BIOLOGICAL PROFILES OF HIGHLY POTENT NOVEL ENDOTHELIN ANTAGONISTS SELECTIVE FOR THE ETA RECEPTOR [J].
IHARA, M ;
NOGUCHI, K ;
SAEKI, T ;
FUKURODA, T ;
TSUCHIDA, S ;
KIMURA, S ;
FUKAMI, T ;
ISHIKAWA, K ;
NISHIKIBE, M ;
YANO, M .
LIFE SCIENCES, 1992, 50 (04) :247-255
[10]   INDUCTION OF ENDOTHELIN-1 GENE BY ANGIOTENSIN AND VASOPRESSIN IN ENDOTHELIAL-CELLS [J].
IMAI, T ;
HIRATA, Y ;
EMORI, T ;
YANAGISAWA, M ;
MASAKI, T ;
MARUMO, F .
HYPERTENSION, 1992, 19 (06) :753-757