Recovery of impaired K+ channels in mesenteric arteries from spontaneously hypertensive rats by prolonged treatment with cholecalciferol
Recovery of impaired K+ channels in mesenteric arteries from spontaneously hypertensive rats by prolonged treatment with cholecalciferol
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DOI：
10.1038/sj.bjp.0702581
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发表时间：
1999-06-01
影响因子：
7.3
通讯作者：
Paiva, TB
中科院分区：
文献类型：
--
作者：
Borges, ACR;Feres, T;Paiva, TB
1研究了胆钙化醇长期治疗自发性高血压大鼠（SHR）后血压下降的机制。每天口服0.125 mg胆钙化醇（kg-1体重）对SHR进行两周治疗，可显著降低收缩压和恒定流速下肠系膜血管床的静息灌注压。2此外，治疗动物对去甲肾上腺素的最大血管收缩反应正常化，肾上腺素浓度-反应曲线的最大效应降低。后一种效应可能是由于受损的与α（2）-肾上腺素受体偶联的Ca 2+依赖性K+通道的恢复，因为它被apamin阻止。3用胆钙化醇治疗还使SHR去内皮化肠系膜动脉的平滑肌细胞膜电位及其对α（2）-肾上腺素能激动剂的超极化反应正常化，4在具有内皮的肠系膜环中，α（2）-肾上腺素能激动剂在SHR以及血压正常的Wistar（NWR）和Wistar京都（WKY）中引起了类似的超极化反应。在非胆钙化醇处理的SHR中，参与这种效应的超极化介质是NO，而在NWR中，它是内皮源性超极化因子（EDI-IF）。胆钙化醇治疗后，SHR平滑肌细胞中α（2）-肾上腺素能激动剂诱导的超极化由EDHF介导，与NWR相同。5我们的研究结果表明，胆钙化醇在SHR中的作用可能是由于血管反应性正常化，通过恢复血管平滑肌细胞膜上的apamin和ATP敏感性K+通道的功能，在SHR中受损。
1 The mechanism responsible for blood pressure reduction in spontaneously hypertensive rats (SHR) after prolonged cholecalciferol treatment was studied. Two-week treatment of SHR with 0.125 mg cholecalciferol kg(-1) body weight per day orally caused significant reductions of systolic blood pressure and of the resting perfusion pressure of the mesenteric vascular bed at constant flow.2 In addition, the treated animals presented a normalization of the maximum vasoconstriction response to noradrenaline and a reduction of the maximum effect of the adrenaline concentration-response curves. This latter effect probably was due to recovery of the impaired Ca2+-dependent K+ channels coupled to alpha(2)-adrenoceptors since it was prevented by apamin.3 The treatment with cholecalciferol also normalized the smooth muscle cell membrane potential of de-endothelialized mesenteric arteries of SHR and their hyperpolarizing responses to alpha(2)-adrenergic agonists, which were depressed in untreated SHR.4 In mesenteric rings with endothelium, alpha(2)-adrenergic agonists caused similar hyperpolarizing responses in the SHR and in normotensive Wistar (NWR) and Wistar Kyoto (WKY). In non cholecalciferol-treated SHR the hyperpolarizing mediator involved in this effect was NO, while in NWR it was the endothelium-derived hyperpolarizing factor (EDI-IF). After cholecalciferol treatment, the hyperpolarization induced by alpha(2)-adrenergic agonists in SHR smooth muscle cells was mediated by EDHF, as in NWR.5 Our results indicate that the hypotensive effect of cholecalciferol in the SHR is probably due to the normalization of vascular reactivity, by restoring the functioning of apamin- and ATP-sensitive K+ channels located in the vascular smooth muscle cell membrane, which are impaired in the SHR.