The Experimental Study On Relationship Between Insulin Resistance And Vascular Endothelium Dependent Pressure Regulation In Rats

Background: The metabolic syndrome ( yndrome X;insulin resistance syndrome) is a cluster of closely associated and interdependent abnormalities, including insulin resistance, compensatory hyperinsulinemia, hyperuricemia, dyslipidemia, and hypertension, and predisposes individuals to type 2 diabetes, hypertension, and coronary heart disease(CHD), and its foundation is considered to be insulin resistance. Although the relationship between insulin resistance and hypertension is not completely clear, a lot of reports have emphasized that endothelium-dependent vascular relaxation dysfunction plays a great role in it. To investigate the relationship and mechanism between endothelium dysfunction and hypertension, we tested the blood pressure and circulatory vasoactive factors in animal models in the present study.Method: fifty male SD rats were randomly divided into 5 groups, each contained 10 rats : the control rats(fed with standard rat chow and had acess to tap water adlibitum);sucrose-fed rats(10% in drinking water);Ins-infused rats (3U/d Insulin Zinc Protamine infused subcutaneously for 60 days);sucrose -fed plus Ins-infused rats A and B(10% in drinking water plus 3U/d Insulin Zinc Protamine infused subcutaneously ). Weight and systolic pressure (by tail cuff method) were tested every week. After about 8 weeks , rats were infused with 1μg/min acetylcholine and 1.5μg/min sodium nitroprusside respectively for 6 minutes through a jugular vein catheter. Systolic pressure was recorded through a carotid artery catheter simultaneously. After recording the time course of the change in systolic pressure, samples of blood were collected rapidly from heart for the measurements of AT II ,insulin, blood glucose, NO, GSH concentration and NOS, SOD activity. sucrose-fed plus Ins-infused rats A and 5 control rats were disposaled at the fifth week ahead for comparison.Results: There is no significantly difference in weight in all groups at the same time during the study (p>0.05) . Systolic blood pressure was found to be significantly higher in Ins-infused rats, sucrose-fed rats and sucrose-fed plus Ins-infused rats compared with control rats from the third week on(155. 33 + 1.87mmHg vs 156. 70 + 2. 41mmHg vs 155. 60 + 2. 59mmHg vs 110.40 + 6.54 mmHg, p<0.05).At the end of study, the descending blood pressure extent after infusing sodium nitropmsside was significantly higher than acetylcholine in Ins-infused rats, sucrose-fed rats and sucrose-fed plus Ins-infused rats B compared with the control and sucrose-fed plus Ins-infused rats A rats (33. 59 + 12. 51mmHg vs. 58. 78 + 22. 24 mmHg, p<0.05;41. 36+12. 78mmHg vs. 63.70 +12. 66mmHg, p<0. 05;35. 07+8. 07mmHg vs. 46. 47 + 13. 09mmHg, p<0. 05;31.73 + 12.17mmHgvs 41. 41 + 14. 39mmHg, p>0. 05;38. 86+8. OlmmHg vs. 43. 24 ±13.18mmHg, p > 0. 05).Plasma glucose level was not found to be significantly elevated (8. 70 + 2. 50mmol/l, 9. 36 + 3. 01 mmol/1, 9. 85 + 2. 32 mmol/1, 8.45 + 0.95 mmol/1, 8.06 + 0.96 mmol/1, p>0.05);the serum NO ,SOD and plasma insulin level were found to be significantly higher in Ins -infused rats, sucrose-fed rats and sucrose-fed plus Ins-infused rats B compared with the control rats (NO: 10. 51+3. 60u mol/1, 10. 75±2. 25u mol/1 vs 15.16 + 2. 91 u mol/1, 17. 43 + 3. 44 u mol/1, 17. 55 + 5. 51 u mol/1, p< 0.05;SOD: 142.82 + 6. 32NU/ml, 138. 71 +4. 72NU/ml VS 153.80 + 3.91 NU/ml, 155. 09±2. 60NU/ml, 150. 59 + 4. 76NU/ml, p<0. 05);plasma insulin level was significantly higher in the experimental groups compared with the control rats (214. 05 + 21. 95U/L, 210.19+13. 55U/L, 148. 48±9. 72U/L, 136. 41+9. 55U/L vs. 35. 78 ± 7. 78U/L , p < 0.05).serum NOS level was Viiaher in Tns-infiisftH rats rnmnared the other four erounsC40. 90 +2.19U/ml VS 33. 27±3. 55U/ml, 32. 92 + 3. 06U/ml, 33. 62 + 1. 89U/ml, 32. 85 +1. 8lU/ml, p<0.05);plasma AT II level was found to be significantly higher in sucrose-fed plus Ins-infused rats B compared with the other four groups (330.11 + 27. 35pg/ml VS 155. 96+19. 55pg/ml, 157. 45 + 6. 52pg/ml, 140. 94 + 20. 44pg/ml, 140. 77 + 15. 26pg/ml, p<0.05);serum GSH level was significantly decreased in Ins-infused rats, sucrose-fed rats and sucrose-fed plus Ins-infused rats compared with the control rats (567. 36 + 25. 05mgGSH/L, 600. 13±49. llmgGSH/L, 570. 31 +29. 22mgGSH/L, 583. 60 + 40. OlmgGSH/L VS 851.19±43.47mgGSH/L, p<0.05).Conclusion: These findings demonstrate that sucrose-fed and (or) insulin -infused can induce endothelium dysfunction and result in hypertension ultimately, endothelium-dependent vascular relaxation dysfunction plays a critical role in the development of hypertension. Decreased nitric oxide bioavailability and oxidative stress and some other vascular active factors are the primary causes in the development of hypertension.