PULMONARY VASCULAR-RESPONSE TO ENDOTHELIN IN RATS

被引:50
作者
RAFFESTIN, B
ADNOT, S
EDDAHIBI, S
MACQUINMAVIER, I
BRAQUET, P
CHABRIER, PE
机构
[1] HOP ANTOINE BECLERE,PHYSIOL LAB,F-92141 CLAMART,FRANCE
[2] FAC MED CRETEIL,INSERM,U296,F-94010 CRETEIL,FRANCE
[3] INST H BEAUFOUR,F-91952 LES ULIS,FRANCE
关键词
PULMONARY CIRCULATION; ENDOTHELIUM; ENDOTHELIUM-DERIVED RELAXING FACTOR(S);
D O I
10.1152/jappl.1991.70.2.567
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
This study investigated the pulmonary vascular response to endothelin (ET) in rats. In conscious rats, an incremental intravenous bolus of ET-1 (100-1,000 pM) caused, after an initial drop in systemic arterial pressure (Psa), a secondary dose-dependent increase of Psa concomitant with a decrease of cardiac output (CO) and heart rate (HR). Pulmonary arterial pressure (Ppa) remained unchanged, and pulmonary vascular resistance (PVR) increased significantly only after 1,000 pM (+40.0 +/- 10.4 at 15 min). Meclofenamate (6 mg/kg iv) did not alter hemodynamic response to ET (300 pM). After autonomic blockade with hexamethonium (6 mg/kg iv) plus atropine (0.75 mg/kg iv), bradycardia response to ET (300 pM) was blocked, but CO decreased, systemic vascular resistance increased, and PVR remained unchanged as in controls. In anesthetized ventilated rats, bolus injections of ET (10-1,000 pM) induced a transient dose-related decrease in compliance (-10.9 +/- 1.8% after 1,000 pM) but no change of conductance. In isolated lungs, Ppa increased at doses > 100 pM, and edema developed in response to 1,000 pM ET. The rise of Ppa in response to 300 pM was not altered by meclofenamate (3.2 x 10(-6) M) but was potentiated by inhibitors of endothelium-derived relaxing factor(s) (EDRF), methylene blue (10(-4) M), pyrogallol (3 x 10(-5) M), and N(G)-monomethyl-L-arginine (6 x 10(-4) M) (3.9 +/- 0.3, 4.6 +/- 0.5, and 5.9 +/- 0.3 mmHg, respectively, compared with 1.5 +/- 0.5 mmHg in control lungs). These results suggest that circulating ET is a more potent constrictor of the systemic circulation than of the pulmonary vascular bed. The pulmonary vasopressor activity of ET appears to be attenuated by the release of EDRFs but not of prostanoids.
引用
收藏
页码:567 / 574
页数:8
相关论文
共 38 条
[1]   ATRIAL NATRIURETIC FACTOR ATTENUATES THE PULMONARY PRESSOR-RESPONSE TO HYPOXIA [J].
ADNOT, S ;
CHABRIER, PE ;
BRUNBUISSON, C ;
VIOSSAT, I ;
BRAQUET, P .
JOURNAL OF APPLIED PHYSIOLOGY, 1988, 65 (05) :1975-1983
[2]   AUGMENTATION OF HYPOXIC PULMONARY VASOCONSTRICTION IN THE ISOLATED PERFUSED RAT LUNG BY INVITRO ANTAGONISTS OF ENDOTHELIUM-DEPENDENT RELAXATION [J].
BRASHERS, VL ;
PEACH, MJ ;
ROSE, CE .
JOURNAL OF CLINICAL INVESTIGATION, 1988, 82 (05) :1495-1502
[3]  
CAIRO J, 1989, FASEB Journal, V3, pA878
[4]   ENDOTHELIN - A NEW FAMILY OF ENDOTHELIUM-DERIVED PEPTIDES WITH WIDESPREAD BIOLOGICAL PROPERTIES [J].
DEGOUVILLE, ACL ;
LIPPTON, HL ;
CAVERO, I ;
SUMMER, WR ;
HYMAN, AL .
LIFE SCIENCES, 1989, 45 (17) :1499-1513
[5]  
DENUCCI G, 1988, P NATL ACAD SCI USA, V85, P9797
[6]   LETHAL ISCHEMIA DUE TO INTRACORONARY ENDOTHELIN IN PIGS [J].
EZRA, D ;
GOLDSTEIN, RE ;
CZAJA, JF ;
FEUERSTEIN, GZ .
AMERICAN JOURNAL OF PHYSIOLOGY, 1989, 257 (01) :H339-H343
[7]   PROSTACYCLIN MEDIATES ANTIAGGREGATORY AND HYPOTENSIVE ACTIONS OF ENDOTHELIN IN ANESTHETIZED BEAGLE DOGS [J].
HERMAN, F ;
MAGYAR, K ;
CHABRIER, PE ;
BRAQUET, P ;
FILEP, J .
BRITISH JOURNAL OF PHARMACOLOGY, 1989, 98 (01) :38-40
[8]   HEMODYNAMIC-EFFECTS OF ENDOTHELIN IN CONSCIOUS RATS [J].
HINOJOSALABORDE, C ;
OSBORN, JW ;
COWLEY, AW .
AMERICAN JOURNAL OF PHYSIOLOGY, 1989, 256 (06) :H1742-H1746
[9]   ENDOTHELIN INDUCES AN INITIAL INCREASE IN CARDIAC-OUTPUT ASSOCIATED WITH SELECTIVE VASODILATION IN RATS [J].
HOFFMAN, A ;
GROSSMAN, E ;
OHMAN, KP ;
MARKS, E ;
KEISER, HR .
LIFE SCIENCES, 1989, 45 (03) :249-255
[10]   METHYLENE-BLUE SELECTIVELY INHIBITS PULMONARY VASODILATOR RESPONSES IN CATS [J].
HYMAN, AL ;
KADOWITZ, PJ ;
LIPPTON, HL .
JOURNAL OF APPLIED PHYSIOLOGY, 1989, 66 (03) :1513-1517