Contribution of nitric oxide produced by inducible nitric oxide synthase to vascular responses of mesenteric arterioles in streptozotocin-diabetic rats
Contribution of nitric oxide produced by inducible nitric oxide synthase to vascular responses of mesenteric arterioles in streptozotocin-diabetic rats
复制标题
DOI：
10.1038/sj.bjp.0705611
复制
发表时间：
2004-01-01
影响因子：
7.3
通讯作者：
Nakayama, K
中科院分区：
文献类型：
--
作者：
Ishikawa, T;Kohno, F;Nakayama, K
1采用活体显微镜观察链脲佐菌素诱导的糖尿病患者肠系膜小动脉的功能变化。从麻醉大鼠身上取出肠系膜，铺在一个腔室中，用Tyrode溶液灌注。所有被试药物均应用于superusing Tyrode溶液中与年龄匹配的对照组相比，糖尿病大鼠对肾上腺素（一种α(1)-肾上腺素受体激动剂）的血管敏感性增强。用一氧化氮合酶（NOS）抑制剂n- g -硝基- l -精氨酸（L-NNA）预孵育肠系膜后，糖尿病大鼠和对照大鼠的苯肾上腺素浓度-反应曲线均向左移动。即使在L-NNA存在的情况下，糖尿病大鼠对苯肾上腺素的敏感性也高于对照组乙酰胆碱对两组大鼠肠系膜小动脉均有松弛作用，但对照组的松弛程度明显大于糖尿病大鼠。然而，l - rna诱导的小动脉收缩在两组之间没有显著差异。相反，诱导型NOS （iNOS）抑制剂s -乙基异硫脲诱导的肠系膜小动脉收缩幅度明显大于对照组用iNOS特异性抗体对肠系膜进行免疫染色，仅在糖尿病大鼠微血管中可见iNOS这些结果表明，stz -糖尿病大鼠肠系膜小动脉对α(1)-肾上腺素能受体刺激的收缩反应是敏化的，而小动脉平滑肌中iNOS的表达在抑制stz -糖尿病大鼠小动脉的基底张力和反应性中起作用。
1 The functional changes in mesenteric arterioles of streptozotocin-induced diabetes were investigated by intravital microscopy. The mesentery was exteriorized from anesthetized rats, spread in a chamber, and superfused with Tyrode solution. All drugs tested were applied to the superfusing Tyrode solution.2 Compared with age-matched controls, the diabetic rats showed enhanced vascular sensitivity to phenylephrine, an alpha(1)-adrenoceptor agonist. The preincubation of the mesentery with N-G-nitro-L-arginine (L-NNA), a nitric oxide synthase (NOS) inhibitor, shifted the phenylephrine-concentration-response curves to the left in both the diabetic and control rats. Even in the presence of L-NNA, the sensitivity to phenylephrine was higher in the diabetic rats than in the control.3 Acetylcholine relaxed the mesenteric arterioles in both groups, but to a significantly greater extent in the control than in the diabetic rats. However, the L-NNA-induced constriction of arterioles did not differ significantly between the groups. In contrast, the amplitude of the constrictions of mesenteric arterioles induced by S-ethylisothiourea, an inducible NOS (iNOS) inhibitor, was significantly greater in the diabetic rats than in the control.4 Immunostaining of the mesentery with a specific antibody for iNOS revealed iNOS in the microvessels of only the diabetic rats.5 These results suggest that constrictor responses to alpha(1)-adrenoceptor stimulation are sensitized in the mesenteric arterioles of STZ-diabetic rats, and that iNOS expressed in the arteriolar smooth muscle plays a role in suppressing the basal tone and the reactivity of the arterioles in STZ-diabetic rats.