Hydrogen sulfide as an endogenous regulator of vascular smooth muscle tone in trout
Hydrogen sulfide as an endogenous regulator of vascular smooth muscle tone in trout
复制标题
DOI：
10.1152/ajpregu.00419.2003
复制
发表时间：
2004-04-01
影响因子：
2.8
通讯作者：
Olson, KR
中科院分区：
文献类型：
--
作者：
Dombkowski, RA;Russell, MJ;Olson, KR
硫化氢(H_2S)是哺乳动物体内的一种内源性血管扩张剂，但在其他脊椎动物中的存在和功能尚不清楚。我们从NaHS中产生了H_2S，并检测了它们对钢头(StEBA)或彩虹鲑鱼(RtEBA)离体鳃动脉的影响。用比色法(CM)和离子选择电极法(ISE)测定虹鱼血浆中的H_2S浓度。NaHS在未受刺激的血管和预缩有卡巴胆碱(Carb)的stEBA中均产生由松弛(第1相)、收缩(第2相)和松弛(第3相)组成的三相反应。K-ATP(+)通道抑制剂格列本脲或环氧合酶、脂氧合酶和细胞色素P-450抑制剂(消炎痛、秦皮乙素和克霉唑)的混合物使未受刺激的血管的stEBA的1相和3相减少，2相增加。用ODQ或NS-2028抑制可溶性鸟苷环化酶可抑制stEBA的3相，但NaHS抑制rtEBA产生cGMP。肌球蛋白轻链激酶抑制剂ML-9可部分抑制STEBA的2相收缩，而L钙通道抑制剂(甲氧维拉帕米)对其无影响，而硝苯地平或细胞外钙的去除可部分抑制rtEBA的收缩。在用Carb和去甲肾上腺素(NE)预收缩的stEBA中，第三相松弛比用KCl或K2SO4收缩的更明显。STEBA 2期和3期反应呈剂量依赖性(EC50分别为1.1+/-1.2×10(-3)M和6.7+/-0.9×10(-5)M；n=7)。NaHS在动脉钢头球、腹膜肠系膜动脉和主干前静脉也有血管活性。虹鱼血浆硫化物浓度为4.0+/-0.3×10(-5)M，n=4(CM)和3.8+/-0.4×10(-5)M(ISE)，n=9(ISE)，与第三阶段EC50相似。由于NaHS在生理血浆浓度下具有显著的血管活性作用，我们认为其可溶性衍生物H_2S是鲑鱼体内一种具有张力活性的内源性血管调节剂。
Hydrogen sulfide (H2S) is an endogenous vasodilator in mammals, but its presence and function in other vertebrates is unknown. We generated H2S from NaHS and examined the effects on isolated efferent branchial arteries from steelhead (stEBA) or rainbow (rtEBA) trout. H2S concentration was measured colorimetrically ( CM) and with ion-selective electrodes (ISE) in rainbow trout plasma. NaHS produced a triphasic response consisting of a relaxation ( phase 1), constriction ( phase 2), and relaxation ( phase 3) in both unstimulated vessels and in stEBA precontracted with carbachol ( Carb). Phase 1 and phase 3 in stEBA were decreased and phase 2 increased in unstimulated vessels by K-ATP(+) channel inhibition ( glibenclamide), or a cocktail of inhibitors of cyclooxygenase, lipoxygenase, and cytochrome P-450 ( indomethacin, esculetin, and clotrimazole). Inhibition of soluble guanylate cyclase with ODQ or NS-2028 inhibited phase 3 in stEBA, although NaHS decreased cGMP production by rtEBA. stEBA phase 2 contractions were partially inhibited by the myosin light chain kinase inhibitor, ML-9, but unaffected by L-type calcium channel inhibition ( methoxyverapamil), whereas contraction in rtEBA was partially inhibited by nifedipine or removal of extracellular calcium. Phase 3 relaxations were more pronounced in stEBA precontracted with Carb and norepinephrine ( NE) than those contracted by KCl or K2SO4. stEBA phase 2 and phase 3 responses were dose dependent (EC50 = 1.1 +/- 1.2 x 10(-3) M and 6.7 +/- 0.9 x 10(-5) M, respectively; n = 7). NaHS was also vasoactive in steelhead bulbus arteriosus, celiacomesenteric arteries, and anterior cardinal veins. Rainbow trout plasma sulfide concentration was 4.0 +/- 0.3 x 10(-5) M, n = 4 ( CM) and 3.8 +/- 0.4 x 10(-5) M, n = 9 ( ISE); similar to phase 3 EC50. Because NaHS has substantial vasoactive effects at physiological plasma concentrations, we propose that its soluble derivative, H2S, is a tonically active endogenous vasoregulator in trout.