IN-VIVO EFFECTS OF ENDOTHELIN A-RECEPTOR AND B-RECEPTOR ANTAGONISTS IN GUINEA-PIGS

被引:20
作者
NAGASE, T
FUKUCHI, Y
MATSUI, H
AOKI, T
MATSUSE, T
ORIMO, H
机构
关键词
BQ-123; BQ-788; TISSUE RESISTANCE; AIRWAY RESISTANCE; ENDOTHELIN-1;
D O I
10.1152/ajplung.1995.268.5.L846
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Endothelin (ET)-1, a novel 21-amino acid constrictor peptide, has been recently reported to have a potential pathophysiological role in asthma. We hypothesized that ET-1 might affect guinea pig lung via different ET receptor subtypes, i.e., ET(A) and ET(B), in vivo. To test this hypothesis, we investigated the effects of ET-1 on airways in anesthetized, open-chest, mechanically ventilated [frequency (f) = 1 Hz; tidal volume (V-T) = 9 ml/kg; positive end-expiratory pressure (PEEP) = 4 cmH(2)O] guinea pigs in the absence or the presence of ET(A) and ET(B) selective antagonists, i.e., BQ-123 and BQ-788, respectively. We affixed alveolar capsules to the lungs to measure alveolar pressure and calculated the elastance of lung (E(L)) and the resistance of lung (R(L)), tissue (R(ti)), and airway (R(aw)) under control conditions and after intravenous administration of ET-1 (10(-8) mol/kg). ET-1 induced a concentration-dependent increase in R(L), R(ti), R(aw), and E(L). BQ-123 (2 mg/kg) partially blocks Delta R(L) and Delta R(aw) during ET-1 induced constriction, while Delta R(ti) and Delta E(L) were not significantly affected. BQ-788 (2 mg/kg) significantly inhibited Delta R(L), Delta R(ti), Delta R(aw), and Delta E(L) during ET-l-induced constriction. The combination of BQ-123 and BQ-788 completely ablated the response to ET-1. These data suggest that both ET receptor subtypes, i.e., ET(A) and ET(B), may have physiological roles in guinea pig airways in response to ET-1, a potential mediator of asthma.
引用
收藏
页码:L846 / L850
页数:5
相关论文
共 26 条
[1]   CLONING AND EXPRESSION OF A CDNA-ENCODING AN ENDOTHELIN RECEPTOR [J].
ARAI, H ;
HORI, S ;
ARAMORI, I ;
OHKUBO, H ;
NAKANISHI, S .
NATURE, 1990, 348 (6303) :730-732
[2]   THE LOW-FREQUENCY DEPENDENCE OF RESPIRATORY SYSTEM RESISTANCE AND ELASTANCE IN NORMAL DOGS [J].
BATES, JHT ;
SHARDONOFSKY, F ;
STEWART, DE .
RESPIRATION PHYSIOLOGY, 1989, 78 (03) :369-382
[3]   EVIDENCE FOR MULTIPLE ENDOTHELIN RECEPTORS IN THE GUINEA-PIG PULMONARY-ARTERY AND TRACHEA [J].
CARDELL, LO ;
UDDMAN, R ;
EDVINSSON, L .
BRITISH JOURNAL OF PHARMACOLOGY, 1992, 105 (02) :376-380
[4]   ALVEOLAR PRESSURE NONHOMOGENEITY DURING SMALL-AMPLITUDE HIGH-FREQUENCY OSCILLATION [J].
FREDBERG, JJ ;
KEEFE, DH ;
GLASS, GM ;
CASTILE, RG ;
FRANTZ, ID .
JOURNAL OF APPLIED PHYSIOLOGY, 1984, 57 (03) :788-800
[5]   EXPRESSION OF ENDOTHELIN-1 IN THE LUNGS OF PATIENTS WITH PULMONARY-HYPERTENSION [J].
GIAID, A ;
YANAGISAWA, M ;
LANGLEBEN, D ;
MICHEL, RP ;
LEVY, R ;
SHENNIB, H ;
KIMURA, S ;
MASAKI, T ;
DUGUID, WP ;
STEWART, DJ .
NEW ENGLAND JOURNAL OF MEDICINE, 1993, 328 (24) :1732-1739
[6]   ENDOTHELIN AND THE RESPIRATORY SYSTEM [J].
HAY, DWP ;
HENRY, PJ ;
GOLDIE, RG .
TRENDS IN PHARMACOLOGICAL SCIENCES, 1993, 14 (01) :29-31
[7]   BIOCHEMICAL AND PHARMACOLOGICAL PROFILE OF A POTENT AND SELECTIVE ENDOTHELIN B-RECEPTOR ANTAGONIST, BQ-788 [J].
ISHIKAWA, K ;
IHARA, M ;
NOGUCHI, K ;
MASE, T ;
MINO, N ;
SAEKI, T ;
FUKURODA, T ;
FUKAMI, T ;
OZAKI, S ;
NAGASE, T ;
NISHIKIBE, M ;
YANO, M .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (11) :4892-4896
[8]   PARTITIONING OF PULMONARY RESISTANCE DURING CONSTRICTION IN THE DOG - EFFECTS OF VOLUME HISTORY [J].
LUDWIG, MS ;
DRESHAJ, I ;
SOLWAY, J ;
MUNOZ, A ;
INGRAM, RH .
JOURNAL OF APPLIED PHYSIOLOGY, 1987, 62 (02) :807-815
[9]   A COMPARISON OF THE DOSE-RESPONSE BEHAVIOR OF CANINE AIRWAYS AND PARENCHYMA [J].
LUDWIG, MS ;
ROMERO, PV ;
BATES, JHT .
JOURNAL OF APPLIED PHYSIOLOGY, 1989, 67 (03) :1220-1225
[10]   EFFECT OF ENDOTHELIN-1 ON PULMONARY RESISTANCE IN RATS [J].
MATSUSE, T ;
FUKUCHI, Y ;
SURUDA, T ;
NAGASE, T ;
OUCHI, Y ;
ORIMO, H .
JOURNAL OF APPLIED PHYSIOLOGY, 1990, 68 (06) :2391-2393