Alonso C, Proto M, Coviello A, Peral de Bruno M
Universidad Nacional de Tucuman, INSIBIO-CONICET Departamento Biomédico Orientacion Fisiologia, Facultad de Medicina Balcarce 32, (4000) San Miguel de Tucuman, Argentina.
Cell Mol Biol (Noisy-le-grand). 2005 Nov 8;51(6):565-72.
We investigated the effect of insulin on basal tone and contractile response in isolated aorta from hypertensive streptozotocin-induced diabetic rats (DR) and the role of endothelium in this response. The effect of insulin was tested in rings of control rats (CR) and DR in different protocols: in basal tone, in the plateau of norepinephrine (NE) or KCl contracted rings and in the response to NE or KCl preincubated with insulin. The role of nitric oxide (NO) on insulin response was investigated in rings treated with L-NAME. We found in DR: a) An endothelium independent-vasorelaxant effect of insulin on basal tone; b) A decreased response to NE (without differences in the sensibility) and to KCl (20 mmol/l) and an improvement of this hyporeactivity by insulin pre-treatment, and c) A potentiated vasorelaxant response of insulin dependent of increased vascular tone. Furthermore, an additional action of insulin on endothelial response through NO-release was observed in precontracted vessels from CR, not observed in DR. Our results support that insulin plays a role in regulation of arterial basal tone from DR by a direct effect on smooth muscle vascular cells exposed to high blood pressure. The vasorelaxant effect of insulin dependent of endothelium is blunted in DR by a reduced endothelial NO production. Our work also suggest that insulin could improve the endothelial function in vessels with increased tone in absence of diabetes.
我们研究了胰岛素对链脲佐菌素诱导的高血压糖尿病大鼠（DR）离体主动脉基础张力和收缩反应的影响，以及内皮在该反应中的作用。在不同实验方案中，检测胰岛素对对照大鼠（CR）和DR血管环的作用：基础张力状态下、去甲肾上腺素（NE）或氯化钾（KCl）收缩血管环的平台期，以及对预先与胰岛素孵育的NE或KCl的反应。在用L - 精氨酸甲酯（L - NAME）处理的血管环中，研究一氧化氮（NO）对胰岛素反应的作用。我们在DR中发现：a）胰岛素对基础张力具有不依赖内皮的血管舒张作用；b）对NE（敏感性无差异）和KCl（20 mmol/L）的反应降低，胰岛素预处理可改善这种反应低下，以及c）胰岛素的血管舒张反应增强，依赖于血管张力增加。此外，在CR的预收缩血管中观察到胰岛素通过释放NO对内皮反应有额外作用，而在DR中未观察到。我们的结果支持胰岛素通过直接作用于暴露于高血压的血管平滑肌细胞，在调节DR的动脉基础张力中发挥作用。DR中胰岛素依赖内皮的血管舒张作用因内皮NO生成减少而减弱。我们的研究还表明，在无糖尿病情况下，胰岛素可改善张力增加的血管的内皮功能。
