Urocortin relaxes rat tail arteries by a PKA‐mediated reduction of the sensitivity of the contractile apparatus for calcium
Urocortin relaxes rat tail arteries by a PKA‐mediated reduction of the sensitivity of the contractile apparatus for calcium
复制标题
DOI：
10.1038/sj.bjp.0704418
复制
发表时间：
2001-12
影响因子：
7.3
通讯作者：
L. Lubomirov;H. Gagov;P. Petkova-Kirova;D. Duridanova;V. Kalentchuk;R. Schubert
中科院分区：
文献类型：
--
作者：
L. Lubomirov;H. Gagov;P. Petkova-Kirova;D. Duridanova;V. Kalentchuk;R. Schubert
Urocortin是一种内源性血管扩张剂，但其血管松弛机制尚不完全清楚。使用等长张力记录和钙荧光测定法验证了涉及到平滑肌钙浓度改变的假设。促肾上腺皮质激素释放因子对42 MMK-PSS预收缩的血管有浓度依赖性的松弛作用(pD28.59±0.06，n=6)。去除血管内皮细胞并不改变其作用，pD2为8.49±0.11，n=5。促肾上腺皮质激素释放因子松弛42 MMK-PSS预收缩的血管的效力弱于尿皮质素(pD26.99±0.28)。N=5)，在100 nM时，Urocortin使42 MMK-PSS预收缩59.6±4.6%(n=8)，与500 n去甲肾上腺素预收缩25.2±6.8%(n=6)。尿皮质激素使张力与细胞内钙的关系显著右移0.33±0.07U/ (n=5)。在0.3 mMRP-8-cPT-cAMPS的存在下，尿皮质激素引起的松弛作用显著减弱。PKA激活剂Sp-5，6- -cBIMPS松弛42 nmMK-PSS预收缩血管(pD24.98±0.07，n=6)。在0.1 mm时，SP-5，6-DCL-cBIMPS使血管收缩85.3%±2.5%(n=5)，但不改变细胞内钙浓度。综上所述，数据表明Urocortin是一种有效的，非内皮依赖性的大鼠尾动脉扩张器，并提示这种作用是通过PKA导致收缩装置对钙的敏感性降低所介导的
Urocortin is an endogenous vasodilator although the mechanism of vasorelaxation is not completely understood. The hypothesis that an alteration of smooth muscle calcium concentration is involved was tested using isometric tension recording and calcium fluorimetry. The relationship between contraction and intracellular calcium was also estimated.Urocortin produced a concentration dependent relaxation (pD28.59±0.06,n=6) of vessels pre‐contracted with a physiological salt solution containing 42 mMKCl (42 mMK‐PSS).Removal of the endothelium did not alter the effect of urocortin, pD2was 8.49±0.11,n=5.Corticotropin‐releasing factor relaxed 42 mMK‐PSS pre‐contracted vessels with less potency compared to urocortin (pD26.99±0.28,n=5).Urocortin at 100 nMrelaxed vessels pre‐contracted with 42 mMK‐PSS by 59.6±4.6% (n=8) and vessels pre‐contracted with 500 nMnoradrenaline by 25.2±6.8% (n=6). Both effects were not accompanied by a change in the intracellular calcium concentration.Urocortin at 100 nMproduced a significant rightward shift of 0.33±0.07 units of normalized intracellular calcium (n=5) of the relationship between tension and intracellular calcium.The urocortin‐induced relaxation was considerably reduced in the presence of 0.3 mMRp‐8‐CPT‐cAMPS, a cyclic AMP‐dependent protein kinase (PKA) inhibitor.The PKA‐activator Sp‐5,6‐DCl‐cBIMPS relaxed 42 mMK‐PSS pre‐contracted vessels (pD24.98±0.07,n=6). Sp‐5,6‐DCl‐cBIMPS at 0.1 mMrelaxed vessels by 85.3±2.5% (n=5), but did not change the intracellular calcium concentration.In conclusion, the data show that urocortin is a potent, endothelium‐independent dilator of rat tail arteries and suggest that this effect is mediated by PKA causing a reduction of the sensitivity of the contractile apparatus for calcium.British Journal of Pharmacology(2001)134, 1564–1570; doi:10.1038/sj.bjp.0704418