Development of endothelin receptors in perinatal rabbit pulmonary resistance arteries

被引:8
作者
Docherty, C [1 ]
MacLean, MR [1 ]
机构
[1] Univ Glasgow, Inst Biomed & Life Sci, Div Neurosci & Biomed Syst, Pulm Res Grp, Glasgow G12 8QQ, Lanark, Scotland
基金
英国惠康基金;
关键词
perinatal rabbit pulmonary resistance arteries; endothelin-1; sarafotoxin S6c; BQ-788; FR139317; SB; 209670; acetylcholine; noradrenaline;
D O I
10.1038/sj.bjp.0701950
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
1 Contractile responses to endothelin-1 (ET-1) and sarafotoxin S6c (S6c) were studied in pulmonary resistance arteries (similar to 320 mu m i.d.) from fetal, 0-24 h, 4 day and 7 day rabbits. The effects of the ETA-selective antagonist FR139317, the selective ETB receptor antagonist BQ-788 and the non-selective ETA/ETB receptor antagonist SE 209670, on these responses, were determined. Acetylcholine-induced vasodilation and noradrenaline-evoked contractions were also examined. 2 ET-1 potency was in the following order (pECS(50) values): fetal (8.7) = 0-24 h (8.8) = 4 day (8.6) > 7 day (8.0). The order of potency for S6c was 7 days (11.1) = 4 days (10.8) > 0-24 h (9.7) > fetal (8.6). Hence, S6c and ET-1 were equipotent in the fetus but S6c was increasingly more potent than ET-1 with increasing age, being some 1000 times more potent by 7 days. By 7 days, responses to ET-1 were also resistant to both FR139317 and BQ-788. FR139317 inhibited responses to ET-1 in vessels from 0-24 h and 4 day, but not fetal, rabbits (pK(b): 6.4 in 4 day rabbits). BQ-788 inhibited responses to ET-1 at all age points except for 7 days (pK(b): 6.7 at 0-24 h; 6.2 at 4 days). BQ-788 inhibited responses to S6c at all age points (pK(b): 8.5 at 4 days). SE 209670 inhibited responses to ET-1 and S6c at 0-24 h and 4 days (pK(b) for ET-1: 8.3 and 8.0 respectively; pK(b) for S6c: 9.2 and 10.2 respectively). 3 Acetylcholine (1 mu M) induced vasodilation at all age points (inhibited by 100 mu M L-N-omega-nitroarginine methylester) although the degree of vasodilation was significantly reduced (similar to 75%) at 0-24 h. Noradrenaline induced contraction at all age points except 7 days and its response was significantly enhanced at 0-24 h. 4 Over the first week of life, the potency of S6c increases whilst that to ET-1 decreases suggesting differential development of responses to ET-1 and S6c and heterogeneity of ETA- or 'ETB-like' receptor-mediated responses. There is no synergism between ETA and ETB receptors at birth but this is established by 7 days. Immediately after birth rabbit Pulmonary Resistance Arteries are hyperresponsive to ET-1 and noradrenaline but exhibit impaired nitric-oxide dependent vasodilation.
引用
收藏
页码:1165 / 1174
页数:10
相关论文
共 62 条
[31]   Heterogeneity of endothelin-B receptors in rabbit pulmonary resistance arteries [J].
MacLean, MR ;
Mackenzie, JF ;
Docherty, CC .
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, 1998, 31 :S115-S118
[32]   ENDOTHELIN ET(A)-RECEPTOR-MEDIATED AND ET(B)-RECEPTOR-MEDIATED VASOCONSTRICTION IN RAT PULMONARY-ARTERIES AND ARTERIOLES [J].
MACLEAN, MR ;
MCCULLOCH, KM ;
BAIRD, M .
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, 1994, 23 (05) :838-845
[33]   Influence of applied tension and nitric oxide on responses to endothelins in rat pulmonary resistance arteries: effect of chronic hypoxia [J].
MacLean, MR ;
McCulloch, KM .
BRITISH JOURNAL OF PHARMACOLOGY, 1998, 123 (05) :991-999
[34]   INFLUENCES OF THE ENDOTHELIUM AND HYPOXIA ON ALPHA(1)-ADRENOCEPTOR-MEDIATED AND ALPHA(2)-ADRENOCEPTOR-MEDIATED RESPONSE IN THE RABBIT ISOLATED PULMONARY-ARTERY [J].
MACLEAN, MR ;
MCCULLOCH, KM ;
MCGRATH, JC .
BRITISH JOURNAL OF PHARMACOLOGY, 1993, 108 (01) :155-161
[35]  
MAJEWSKI H, 1984, BLOOD VESSELS, V21, P194
[36]   ENDOTHELIN-1-21 PLASMA-LEVELS ON THE FIRST AND 4TH POSTPARTUM DAY IN NORMAL FULL-TERM NEONATES [J].
MALAMITSIPUCHNER, A ;
ECONOMOU, E ;
SEVASTIADOU, S ;
EFSTATHOPOULOS, T ;
NICOLOPOULOS, D .
DEVELOPMENTAL PHARMACOLOGY AND THERAPEUTICS, 1993, 20 (3-4) :195-198
[37]   MOLECULAR AND CELLULAR MECHANISM OF ENDOTHELIN REGULATION - IMPLICATIONS FOR VASCULAR FUNCTION [J].
MASAKI, T ;
KIMURA, S ;
YANAGISAWA, M ;
GOTO, K .
CIRCULATION, 1991, 84 (04) :1457-1468
[38]  
MASAKI T, 1994, PHARMACOL REV, V46, P137
[39]   Endothelin receptors mediating contraction of rat and human pulmonary resistance arteries: effect of chronic hypoxia in the rat [J].
McCulloch, KM ;
Docherty, C ;
MacLean, MR .
BRITISH JOURNAL OF PHARMACOLOGY, 1998, 123 (08) :1621-1630
[40]   Endothelin(B) receptor-mediated contraction in human pulmonary resistance arteries [J].
McCulloch, KM ;
Docherty, CC ;
Morecroft, I ;
MacLean, MR .
BRITISH JOURNAL OF PHARMACOLOGY, 1996, 119 (06) :1125-1130