胰岛素对自发性高血压大鼠离体主动脉的舒张作用及机制

Vasodilatory effect and mechanism of insulin on isolated aorta in normal and spo ntaneously hypertensive rats

目的 :探讨自发性高血压大鼠 (SHR)的动脉血管对胰岛素 (Ins)反应性的改变及其主要机制。方法 :采用离体血管灌流方法 ,对比观察成年 (15周龄 )和幼年 (5周龄 )自发性高血压大鼠以及成年和幼年正常大鼠 (WKY)的胸主动脉环 ,在未加干预或施加干预 (机械法去除血管内皮或用一氧化氮合酶抑制剂处理 )后对 Ins反应的变化。结果 :Ins(1～ 12 0 U/ L )对成年和幼年 WKY胸主动脉血管具有舒张作用 ,而对相应年龄 SHR的舒张作用均降低。在12 0 U/ L Ins时 ,成年 SHR和 WKY大鼠的血管收缩率为 :73 %± 4% vs2 9%± 4% ,P<0 .0 1;幼年 SHR和 WKY大鼠的血管收缩率为 :61%± 5% vs 3 2 %± 6% ,P<0 .0 1。去除内皮或用 10μm ol/ L一氧化氮合酶抑制剂处理后 ,Ins对成年和幼年 WKY胸主动脉血管的舒张作用均降低 ,且和相应周龄的 SHR无显著差异。此外 ,成年 SHR动脉环在去除内皮前后对 Ins的反应无显著差异 (73 %± 4% vs82 %± 6% ,P>0 .0 5) ,而幼年 SHR在去除内皮后对Ins的反应显著降低 (61%± 5% vs 78%± 5% ,P<0 .0 5)。结论 :Ins对血管的舒张作用是部分通过内皮和一氧化氮 (NO)介导的。成年 SHR血管内皮细胞功能受损 ,而幼年 SHR内皮功能无明显损害。此外 ,两者可能都存在胰岛素抵抗的状态 ,从而降低了血管对

AIM: To observe the effect of insulin on vascular tone in hyp ertension conditions. METHODS: SHR before (5 weeks old) and after (15 weeks old) the esta blishment of hype rtension and two groups of age- and sex-matched WKY were studied. The vasodila tion induced by increasing doses of insulin (1 to 120 U/L) was tested on aortic rings. RESULTS: The va sodilation evoked by insulin was impaired in both the 5-week-old and 15-week -old SHR compared with the age- and sex-matched WKY[% of contraction(in 120 U/L Ins): 5-week-old, SHR 61±5 vs WKY 32±6, P <0.01; 15-week-o ld,SHR 73±4 vs WKY 29±4, P <0.01]. After the removal of endotheliu m or the inhibition of endothelial NO synthase, the vasodilati on evoked by the hormone was blunted and became similar between hypertensive and normotensive rats in both the 5-week-old and 15-week-old groups. CONC LUSION: ① Insulin has inhibitory effect on vascular tone. The effect is, partly at least, endothelium or NO-dependent. ② The vasorelaxant responses to insulin were sign ificantly blunted in both the young and adult SHR, suggesting that endothelium m ay be impaired in hypertension and the resistant states towards insulin may exis t even before the occurrence of hypertension in SHR.