| Insulin is a hormone which contains 51 amino acids and secreted by B cells of pancreas. The effects of insulin on cardiovascular system have being a subject of intensive study. It was found recently that insulin exerts inhibitory effect on vascular tone. On the other hand, vascular endothelial cells can synthesis and release nitric oxide (NO) which result in the relaxation of blood vessels. However, the relationship of the vasodilatory effect of insulin with endothelial production of NO and the mechanism of insulin on vascular mechanical activity in the condition of hypertension remain unknown.The aims of this study, therefore, were to observe and compare the effect of insulin on aortic rings from normal and hypertensive rats in vitro, and further to investigate its potential mechanisms. Experimental animals were WKY andSHR aged 5 to 6 weeks (young) and 12 to 15 weeks (adult), respectively. The experiments are consisted of: 1.The effect of cumulative application of insulin on the norepinephrine-induced contraction in isolated aortic rings from both WKY and SHR. 2. The effect of cumulative application of norepinephrine in control conditions and during exposure to insulin on isolated aortic rings from both WKY and SHR.The main results are as follows:1. The blood pressure was significantly higher in SHR compared with WKY in the adult rats (178±6 vs. 116 ± 4 mmHg, P<0.01), but not in the young rats (121 ±2 vs. 114±4 mmHg, P>0.05).2. The effect of cumulative application of insulin on the norepinephrine-induced contraction in isolated aortic rings from both WKY and SHR.The vasodilations induced by increasing doses of insulin (1 to 120 mU/ml) were tested on aortic rings. Compared with age-matched SHR, vasodilations evoked by insulin were more obvious in both the adult (% of maximal contraction: SHR 73±4 vs. WKY 29 ± 4%,P<0.01) and young (SHR 61 ±5 vs. WKY 32 ± 6%, P<0.01) WKY groups. After the removal of the aortic vascular endothelium or in the presence of the NO synthase inhibitor-L-NMMA, the vasodilations evoked by the hormone were blunted in WKY and became similar between SHR and WKY rats in both the two age groups.3. The effect of cumulative application of norepinephrine in control conditions and during exposure to insulin on isolated aortic rings from both WKY and SHR.The effects of norepinephrine in increasing concentrations (10-9 to 10-6mol/L) on the vascular reactivity of isolated aortic rings in control conditions and after 30 min of exposure to insulin (120 mU/ml) were examined in another experiment. The exposure of aortic rings to insulin reduced the vasoconstrictions caused by norepinephrine in both the adult (maximal vasoconstriction: 1461 ± 114 vs. 956 ± 100 mg, P<0.01) and young (1260±141 vs. 900 ± 128 mg,P<0.01 ) WKY groups. In different aged SHR, insulin failed to modify the vascular response to norepinephrine (adult 1300 ± 268 vs. 1063 ± 247 mg, P>0.05; young 692 ± 297 vs. 808 ±280 mg, P>0.05). After the removal of endothelium or in the presence of L-NMMA, vasoconstrictions could not be inhibited by insulin in either the adult or young WKY.In conclusion, our data demonstrate that: 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 significantly blunted in both the young and adult SHR, suggesting that endothelium may be impaired in hypertension and the resistent states towards insulin may exist even before the occurrence of hypertension in SHR.
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