Effects of angiotensin II receptor antagonist on impaired endothelium-dependent and endothelium-independent relaxations in type II diabetic rats
Effects of angiotensin II receptor antagonist on impaired endothelium-dependent and endothelium-independent relaxations in type II diabetic rats
复制标题
血管紧张素II受体拮抗剂对II型糖尿病大鼠内皮依赖性和内皮非依赖性舒张受损的影响
作者：
Hideyuki Oniki;K. Fujii;Yasuo Kansui;K. Goto;M. Iida
背景糖尿病是心血管疾病的重要危险因素，血管扩张功能障碍可能是糖尿病血管并发症的重要原因。我们先前证明，血管紧张素II受体阻滞剂(ARB)可纠正内皮衍生超极化因子(EDHF)介导的高血压或衰老相关的动脉超极化和松弛，部分地不依赖于血压。目的检测2型糖尿病Goto-Kakizaki大鼠动脉血管内皮细胞生长因子(EDHF)介导的以及非内皮依赖性的舒张性是否会发生改变，以及ARB能否纠正这些改变。方法给Goto-Kakizaki大鼠灌胃ARB坎地沙坦或联用肼和氢氯噻嗪8周，从10周龄开始。记录离体肠系膜动脉的膜电位和收缩反应。结果两种治疗方法的降压效果相当。与年龄匹配的Wistar大鼠相比，未治疗的Goto-Kakizaki大鼠肠系膜动脉的乙酰胆碱诱导的、EDHF介导的超极化和松弛明显受损，ARB和联合治疗都不能改善这些反应。另一方面，在用高钾溶液预收缩的环中评估的内皮衍生一氧化氮的松弛在四组中是相似的。未治疗的Goto-Kakizaki大鼠对一氧化氮供体硝普钠和ATP敏感性钾通道开放剂左克罗卡林的松弛也受到损害，而经治疗的Goto-Kakizaki大鼠对硝普钠的反应部分改善。结论在2型糖尿病大鼠的动脉中，EDHF介导的超极化和舒张性以及非内皮依赖性的舒张性均受到损害，而降压治疗加或不加ARB可部分纠正NO供体的内皮非依赖性的舒张性，但不能纠正EDHF介导的反应。
Background Diabetes mellitus is an important risk factor for cardiovascular diseases, and vasodilator dysfunction may contribute to vascular complications in diabetes. We previously demonstrated that the angiotensin II receptor blocker (ARB) corrected the impaired endothelium-derived hyperpolarizing factor (EDHF)-mediated arterial hyperpolarization and relaxation associated with hypertension or aging, partially independently of blood pressure. Objective To test whether EDHF-mediated, as well as endothelium-independent, relaxations would be altered in arteries from type II diabetic Goto–Kakizaki rats, and whether ARB would correct these alterations. Methods Goto–Kakizaki rats were treated with either the ARB candesartan or a combination of hydralazine and hydrochlorothiazide for 8 weeks, beginning at 10 weeks of age. Membrane potentials and contractile responses were recorded from the isolated mesenteric arteries. Results The two treatments lowered blood pressure comparably. Acetylcholine-induced, EDHF-mediated hyperpolarization and relaxation in mesenteric arteries were markedly impaired in untreated Goto–Kakizaki rats compared with age-matched Wistar rats, and neither ARB nor the combination therapy improved these responses. On the other hand, relaxations to endothelium-derived nitric oxide, assessed in rings precontracted with high potassium solution, were similar among the four groups. Relaxation to the nitric oxide donor sodium nitroprusside and that to levcromakalim, an ATP-sensitive K+-channel opener, were also impaired in untreated Goto–Kakizaki rats, and the response to sodium nitroprusside was partially improved in treated Goto–Kakizaki rats. Conclusions These findings suggest that EDHF-mediated hyperpolarization and relaxation and endothelium-independent relaxations are both impaired in arteries of type II diabetic rats, and antihypertensive treatment with or without ARB partially corrects endothelium-independent relaxations to the nitric oxide donor but not EDHF-mediated responses.
登录
查看更多内容
影响因子：
37.8
作者：
Lund, DD;Faraci, FM;Heistad, DD
通讯作者：
Heistad, DD
影响因子：
20.1
作者：
Paul A. Zimmermann;H. Knot;Andra S. Stevenson;Mark Nelson
通讯作者：
Paul A. Zimmermann;H. Knot;Andra S. Stevenson;Mark Nelson
影响因子：
20.1
作者：
Campbell, WB;Gebremedhin, D;Harder, DR
通讯作者：
Harder, DR
影响因子：
7.7
作者：
Gunnett, CA;Heistad, DD;Faraci, FM
通讯作者：
Faraci, FM
影响因子：
--
作者：
MAYHAN, WG;FARACI, FM
通讯作者：
FARACI, FM