EFFECTS OF THE NEUTRAL ENDOPEPTIDASE INHIBITOR, SQ 28,603, ON REGIONAL HEMODYNAMIC-RESPONSES TO ATRIAL-NATRIURETIC-PEPTIDE OR PROENDOTHELIN-1 [1-38] IN CONSCIOUS RATS

被引:21
作者
GARDINER, SM
KEMP, PA
BENNETT, T
机构
[1] Department of Physiology and Pharmacology, University of Nottingham Medical School, Queen's Medical Centre, Nottingham
关键词
RAT ATRIAL NATRIURETIC PEPTIDE [1-28; PROENDOTHELIN-1 [1-38; NEUTRAL ENDOPEPTIDASE INHIBITOR; SQ 28,603; HEMODYNAMICS;
D O I
10.1111/j.1476-5381.1992.tb14312.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
1 Regional haemodynamic responses to atrial natriuretic peptide (ANP, 0.5 nmol kg-1) or proendothelin-1 [1-38] (1.0 nmol kg-1) were assessed in the same conscious Long Evans rats before and 20 min after administration of the novel neutral endopeptidase (NEP) inhibitor, SQ 28,603 (50 mg kg-1, i.v.). In a separate experiment, responses to endothelin-1 (0.5 nmol kg-1), angiotensin I (0.25 nmol kg-1) and angiotensin II (0. 12 nmol kg-1) were measured before and after administration of SQ 28,603. 2 SQ 28,603 alone had no significant cardiovascular effects but caused significant prolongation of the hypotensive, tachycardic and renal and mesenteric vasoconstrictor effects of ANP. However, the early vasodilator and late vasoconstrictor responses in the hindquarters were not affected significantly. 3 SQ 28,603 caused significant attenuation of the pressor effects of proendothelin-1 [1-38] but the associated bradycardia was unchanged. SQ 28,603 caused a significant inhibition of the renal and mesenteric vasoconstrictor effects of proendotlielin-1 and also inhibited the initial vasodilator and subsequent vasoconstrictor responses in the hindquarters vascular bed. 4 SQ 28,603 had no significant effects on the haemodynamic responses to endothelin-1, angiotensin I, or angiotensin II. 5 The results are consistent with SQ 28,603 not only inhibiting NEP that is involved in the degradation of ANP, but also suppressing activity of the enzyme involved in the conversion of proendothelin-1 [1-38] to endothelin-1.
引用
收藏
页码:180 / 186
页数:7
相关论文
共 34 条
[1]   EFFECT OF SYMPATHECTOMY ON RENAL AND CIRCULATORY ACTION OF ATRIAL-NATRIURETIC-PEPTIDE [J].
ALLEN, DE .
AMERICAN JOURNAL OF PHYSIOLOGY, 1990, 259 (06) :R1274-R1280
[2]   CLEARANCE FUNCTION OF TYPE-C RECEPTORS OF ATRIAL NATRIURETIC FACTOR IN RATS [J].
ALMEIDA, FA ;
SUZUKI, M ;
SCARBOROUGH, RM ;
LEWICKI, JA ;
MAACK, T .
AMERICAN JOURNAL OF PHYSIOLOGY, 1989, 256 (02) :R469-R475
[3]   SYMPATHECTOMY FAILS TO REVEAL PROMINENT VASODILATION BY ATRIAL-NATRIURETIC-FACTOR [J].
BARBEE, RW ;
HARRISONBERNARD, LM ;
ZIMMERMAN, RS ;
TRIPPODO, NC ;
FROHLICH, ED .
HYPERTENSION, 1990, 15 (06) :888-893
[4]   INFLUENCE OF C-ANF RECEPTOR AND NEUTRAL ENDOPEPTIDASE ON PHARMACOKINETICS OF ANF IN RATS [J].
CHIU, PJS ;
TETZLOFF, G ;
ROMANO, MT ;
FOSTER, CJ ;
SYBERTZ, EJ .
AMERICAN JOURNAL OF PHYSIOLOGY, 1991, 260 (01) :R208-R216
[5]   NO MAJOR ROLE FOR ATRIAL-NATRIURETIC-PEPTIDE IN THE VASODILATOR RESPONSE TO ENDOTHELIN-1 IN THE SPONTANEOUSLY HYPERTENSIVE RAT [J].
FOZARD, JR ;
PART, ML .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1990, 180 (01) :153-159
[6]   ENDOTHELIN IS A POTENT SECRETAGOGUE FOR ATRIAL NATRIURETIC PEPTIDE IN CULTURED RAT ATRIAL MYOCYTES [J].
FUKUDA, Y ;
HIRATA, Y ;
YOSHIMI, H ;
KOJIMA, T ;
KOBAYASHI, Y ;
YANAGISAWA, M ;
MASAKI, T .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1988, 155 (01) :167-172
[7]   INHIBITION OF BIOLOGICAL ACTIONS OF BIG ENDOTHELIN-1 BY PHOSPHORAMIDON [J].
FUKURODA, T ;
NOGUCHI, K ;
TSUCHIDA, S ;
NISHIKIBE, M ;
IKEMOTO, F ;
OKADA, K ;
YANO, M .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1990, 172 (02) :390-395
[8]   REGIONAL HEMODYNAMIC-EFFECTS OF ATRIAL NATRIURETIC PEPTIDE OR CAPTOPRIL IN BRATTLEBORO RATS [J].
GARDINER, SM ;
COMPTON, AM ;
BENNETT, T .
AMERICAN JOURNAL OF PHYSIOLOGY, 1988, 255 (05) :R737-R743
[9]   REGIONAL HEMODYNAMIC-EFFECTS OF CALCITONIN GENE-RELATED PEPTIDE [J].
GARDINER, SM ;
COMPTON, AM ;
BENNETT, T .
AMERICAN JOURNAL OF PHYSIOLOGY, 1989, 256 (02) :R332-R338
[10]   REGIONAL AND CARDIAC HEMODYNAMIC-RESPONSES TO GLYCERYL TRINITRATE, ACETYLCHOLINE, BRADYKININ AND ENDOTHELIN-1 IN CONSCIOUS RATS - EFFECTS OF NG-NITRO-L-ARGININE METHYL-ESTER [J].
GARDINER, SM ;
COMPTON, AM ;
KEMP, PA ;
BENNETT, T .
BRITISH JOURNAL OF PHARMACOLOGY, 1990, 101 (03) :632-639