Antihypertensive treatment improves endothelium-dependent hyperpolarization in the mesenteric artery of spontaneously hypertensive rats.
Antihypertensive treatment improves endothelium-dependent hyperpolarization in the mesenteric artery of spontaneously hypertensive rats.
复制标题
抗高血压治疗可改善自发性高血压大鼠肠系膜动脉内皮依赖性超极化。
DOI：
10.1161/01.cir.98.2.175
复制
发表时间：
1998
期刊：
影响因子：
37.8
通讯作者：
Masatoshi Fujishima
中科院分区：
文献类型：
--
作者：
U. Onaka;K. Fujii;Isao Abe;Masatoshi Fujishima
背景
血管内皮释放内皮源性超极化因子（EDHF）。在6 ~ 8月龄自发性高血压大鼠（SHR）的肠系膜动脉中，乙酰胆碱通过EDHF引起的超极化反应受到损害。
方法和结果
我们确定降压治疗是否可以改善EDHF介导的SHR反应。从8至9个月大开始，动物接受依那普利（40 mg x kg（-1）x d（-1））（SHR-E）或肼苯哒嗪（25 mg x kg（-1）x d（-1））和氢氯噻嗪（7.5 mg x kg（-1）x d（-1））（SHR-H）联合治疗3个月。对照组为年龄匹配的SHR（SHR-Cs）和Wistar京都大鼠（WKY）。两种治疗方法降低血压的程度相当。经治疗的SHR肠系膜动脉中乙酰胆碱诱导的超极化改善至与WKY相当的水平（乙酰胆碱10（-5）mol/L+去甲肾上腺素10（-5）mol/L：SHR-E，-14.4 +/- 1.8; SHR-H，-12.0 +/- 1.3; SHR-C，-7.2 +/- 1.2; WKY，-13.3 +/- 2.3 mV）。在去甲肾上腺素收缩的环中，通过对N（G）-硝基-L-精氨酸的乙酰胆碱抗性的舒张来评估EDHF介导的舒张，在治疗的SHR中显著改善（最大舒张：SHR-E，79.3+/-3.2%; SHR-H，47.4+/-8.6%; SHR-C，4.8+/-2.4%;和WKY，45.1+/-6.0%）。当用77 mmol/LKCl收缩环以消除EDHF反应时，四组间对乙酰胆碱的舒张作用无差异。类似地，对左克罗卡林（一种K+通道开放剂）的超极化和舒张在各组之间相当。
结论
降压治疗改善EDHF介导的超极化和舒张在SHR的肠系膜动脉，而NO介导的舒张没有出现调制的药物治疗。因此，EDHF系统的改变可能在SHR的内皮功能障碍及其药物治疗的改善中起关键作用。
BACKGROUND
The vascular endothelium releases endothelium-derived hyperpolarizing factor (EDHF). The mesenteric arteries of 6- to 8-month-old spontaneously hypertensive rats (SHRs) exhibit an impairment of the hyperpolarization induced by acetylcholine via EDHF.
METHODS AND RESULTS
We determined whether antihypertensive treatment can improve EDHF-mediated responses in SHRs. Beginning at age 8 to 9 months, the animals were treated with either enalapril (40 mg x kg(-1) x d(-1)) (SHR-Es) or a combination of hydralazine (25 mg x kg(-1) x d(-1)) and hydrochlorothiazide (7.5 mg x kg(-1) x d(-1)) (SHR-Hs) for 3 months. The control groups were age-matched SHRs (SHR-Cs) and Wistar Kyoto rats (WKYs). The two treatments lowered the blood pressure to comparable extents. The acetylcholine-induced hyperpolarization in the mesenteric artery of treated SHRs improved to a level comparable to that in WKYs (acetylcholine 10(-5) mol/L with norepinephrine 10(-5) mol/L: SHR-E, -14.4 +/- 1.8; SHR-H, -12.0 +/- 1.3; SHR-C, -7.2 +/- 1.2; and WKY, -13.3 +/- 2.3 mV). EDHF-mediated relaxation, as assessed by relaxation to acetylcholine resistant to N(G)-nitro-L-arginine in norepinephrine-contracted rings, was markedly improved in treated SHRs (maximal relaxation: SHR-E, 79.3+/-3.2%; SHR-H, 47.4+/-8.6%; SHR-C, 4.8+/-2.4%; and WKY, 45.1+/-6.0%). When the rings were contracted with 77 mmol/L KCl to eliminate EDHF response, no difference was found in relaxation to acetylcholine among the four groups. Similarly, the hyperpolarization and relaxation to levcromakalim, a K+ channel opener, were comparable among the groups.
CONCLUSIONS
Antihypertensive treatment improved EDHF-mediated hyperpolarization and relaxation in the mesenteric artery in SHRs, whereas NO-mediated relaxation did not appear to be modulated by drug therapy. Thus, alterations in the EDHF system may play a pivotal role in endothelial dysfunction and its improvement with drug therapy in SHRs.
影响因子：
20.1
作者：
Campbell, WB;Gebremedhin, D;Harder, DR
通讯作者：
Harder, DR
影响因子：
8.3
作者：
LUSCHER, TF;VANHOUTTE, PM
通讯作者：
VANHOUTTE, PM