Non-genomic mechanism of 17 beta-oestradiol-induced inhibition of contraction in mammalian vascular smooth muscle

被引:137
作者
Kitazawa, T [1 ]
Hamada, E [1 ]
Kitazawa, K [1 ]
Gaznabi, AKM [1 ]
机构
[1] UNIV TOKYO,FAC MED,DEPT INTERNAL MED 2,BUNKYO KU,TOKYO 113,JAPAN
来源
JOURNAL OF PHYSIOLOGY-LONDON | 1997年 / 499卷 / 02期
关键词
D O I
10.1113/jphysiol.1997.sp021944
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
1. 17 beta-Oestradiol (E2) at 0.1-10 mu M directly inhibited various tonic and phasic smooth muscle contractions. The mechanism(s) of oestrogen-induced inhibition of contraction was studied using intact and permeabilized strips and isolated single cells of smooth muscle. 2. In endothelium-denuded vascular smooth muscle, E2 attenuated high lif-induced force development and myosin light chain phosphorylation, and produced rapid and reversible relaxation. There were no significant differences in these inhibitory effects between tissue types (femoral artery vs. portal vein), species (rat vs. rabbit) or sexes. 3. The inhibitory potencies of several steroidal and non-steroidal oestrogen analogues were examined and their effects were for the most part stereo-specific. However, two steroids with negligible affinities for the nuclear oestrogen receptor also strongly inhibited high K+-induced contraction. 4. Genomic modulators including a protein synthesis inhibitor, an RNA synthesis inhibitor, and oestrogen receptor antagonists did not affect the inhibitory actions of E2. Inhibitors of cyclic nucleotide-dependent protein kinases did not reduce the E2 effect. 5. Ca2+ release from intracellular stores by agonists and by inositol 1,4,5-trisphosphate (IP3) does not appear to be modulated by E2. Neither pretreatment with ryanodine nor with thapsigargin affected the EB-induced inhibition of high K+-induced contraction. 6. E2 had no effect on either normal or GTP gamma S-increased Ca2+ sensitivity of the regulatory and contractile apparatus. 7. E2 and its analogues rapidly inhibited voltage-dependent L-type Ca2+ channel currents in isolated smooth muscle cells. Repetitive stimulation was not required for E2-induced inhibition of the currents. 8. This study strongly suggests that at pharmacological concentrations oestrogen primarily reduces Ca2+ influx through inhibition of L-type Ca2+ channels in a non-genomic manner and decreases myosin light chain phosphorylation and contraction of smooth muscle.
引用
收藏
页码:497 / 511
页数:15
相关论文
共 39 条
[1]   ESTROGEN AND CORONARY HEART-DISEASE IN WOMEN [J].
BARRETTCONNOR, E ;
BUSH, TL .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 1991, 265 (14) :1861-1867
[2]   EFFECTS OF DIETHYLSTILBESTROL AND OVARIAN STEROIDS ON CONTRACTILE RESPONSES AND CALCIUM MOVEMENTS IN RAT UTERINE SMOOTH-MUSCLE [J].
BATRA, S ;
BENGTSSON, B .
JOURNAL OF PHYSIOLOGY-LONDON, 1978, 276 (MAR) :329-342
[3]   NITRENDIPINE BLOCK OF CARDIAC CALCIUM CHANNELS - HIGH-AFFINITY BINDING TO THE INACTIVATED STATE [J].
BEAN, BP .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1984, 81 (20) :6388-6392
[4]  
BLACKMORE PF, 1991, J BIOL CHEM, V266, P18655
[5]   CARDIOVASCULAR PROTECTION BY ESTROGEN - A CALCIUM-ANTAGONIST EFFECT [J].
COLLINS, P ;
ROSANO, GMC ;
JIANG, CW ;
LINDSAY, D ;
SARREL, PM ;
POOLEWILSON, PA .
LANCET, 1993, 341 (8855) :1264-1265
[6]   The pharmacological actions of diethyl-stilboestrol and other oestrogenic and non-oestrogenic substances [J].
Dawson, RF ;
Robson, JM .
JOURNAL OF PHYSIOLOGY-LONDON, 1939, 95 (03) :420-430
[7]   The vascular protective effects of estrogen [J].
Farhat, MY ;
Lavigne, MC ;
Ramwell, PW .
FASEB JOURNAL, 1996, 10 (05) :615-624
[8]   A LOW-AFFINITY ESTROGEN-BINDING SITE IN PREGNANT RAT UTERI - ANALYSIS AND PARTIAL-PURIFICATION [J].
GRAY, WGN ;
BISWAS, EE ;
BASHIRELAHI, N ;
BISWAS, SB .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (24) :11502-11506
[9]   IMPROVED PATCH-CLAMP TECHNIQUES FOR HIGH-RESOLUTION CURRENT RECORDING FROM CELLS AND CELL-FREE MEMBRANE PATCHES [J].
HAMILL, OP ;
MARTY, A ;
NEHER, E ;
SAKMANN, B ;
SIGWORTH, FJ .
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 1981, 391 (02) :85-100
[10]   AGONIST-DEPENDENT MODULATION OF CA-2+ SENSITIVITY IN RABBIT PULMONARY-ARTERY SMOOTH-MUSCLE [J].
HIMPENS, B ;
KITAZAWA, T ;
SOMLYO, AP .
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 1990, 417 (01) :21-28