Departamento de Fisiología, Facultad de Veterinaria, Universidad de la República, Montevideo 11600, Uruguay.
J Anim Sci. 2012 Apr;90(4):1192-200. doi: 10.2527/jas.2011-4129. Epub 2011 Nov 7.
To test the effect of insulin on renal perfusion and the participation of NO and PG as mediators of this response, renal blood flow (RBF) was measured in sheep (n = 8) implanted with ultrasonic flow probes around renal arteries and with a systemic arterial pressure (SAP, n = 4) telemetry device. Three protocols were performed: 1) RBF and SAP were recorded (0800 to 1800 h) in fed and fasted sheep, with the latter receiving intravenous (i.v.) infusions (0.5 mL/min) of insulin at 2 or 6 mU/(kg·min); 2) fasted sheep received i.v. infusions of either an inhibitor of NO synthesis (N(G)-nitro-L-arginine methyl ester, L-NAME) alone [0.22 mg/(kg·min), 1000 to 1200 h] or L-NAME (1000 to 1200 h) + insulin during the second hour (6 mU/(kg·min), 1100 to 1200 h); and 3) the same protocol was followed as in protocol 2, substituting L-NAME with ketoprofen [0.2 mg/(kg·min)], a cyclooxygenase inhibitor. In all protocols, plasma insulin and glucose were determined. During insulin administration, euglycemia was maintained and hypokalemia was prevented by infusing glucose and KCl solutions. After the onset of meals, a long-lasting 18% increase in RBF and a 48% insulin increase were observed (P < 0.05), without changes in SAP. Low- and high-dose insulin infusions increased RBF by 19 and 40%, respectively (P < 0.05). As after meals, the increases in RBF lasted longer than the insulin increase (P < 0.05). The L-NAME infusion decreased RBF by 15% (P < 0.05); when insulin was added, RBF increased to preinfusion values. Ketoprofen decreased RBF by 9% (P < 0.05); when insulin was added, RBF increased to 13% above preinfusion values (P < 0.05). In no case was a modification in SAP or glucose noted during the RBF changes. In conclusion, insulin infusion mimics the meal-dependent increase in RBF, independent of SAP, and lasts longer than the blood insulin plateau. The RBF increase induced by insulin was only partially prevented by L-NAME. Ketoprofen failed to prevent the insulin-dependent RBF increase. Both facts suggested that complementary vasodilatatory agents accounted for the insulin effect on sheep renal hemodynamics.
为了测试胰岛素对肾灌注的影响以及 NO 和 PG 作为这种反应的介导物的参与，我们在植入了超声血流探头的绵羊（n=8）中测量了肾血流量（RBF），并植入了系统动脉压（SAP，n=4）遥测设备。进行了三个方案：1）在进食和禁食的绵羊中记录 RBF 和 SAP（0800 至 1800 h），后者以 2 或 6 mU/（kg·min）的速度静脉内（i.v.）输注胰岛素；2）禁食绵羊接受单独的一氧化氮合成抑制剂（N（G）-硝基-L-精氨酸甲酯，L-NAME）的静脉内输注[0.22 mg/（kg·min），1000 至 1200 h]或 L-NAME（1000 至 1200 h）+胰岛素在第二个小时（6 mU/（kg·min），1100 至 1200 h）；3）按照方案 2 进行相同的方案，用酮洛芬[0.2 mg/（kg·min）]代替 L-NAME，酮洛芬是一种环氧化酶抑制剂。在所有方案中，均测定血浆胰岛素和葡萄糖。在胰岛素给药期间，通过输注葡萄糖和 KCl 溶液来维持正常血糖和预防低钾血症。进餐后，RBF 持续增加 18%，胰岛素增加 48%（P < 0.05），SAP 无变化。低剂量和高剂量胰岛素输注分别使 RBF 增加 19%和 40%（P < 0.05）。与进餐后一样，RBF 的增加持续时间长于胰岛素的增加（P < 0.05）。L-NAME 输注使 RBF 减少 15%（P < 0.05）；当添加胰岛素时，RBF 增加到输注前的值。酮洛芬使 RBF 减少 9%（P < 0.05）；当添加胰岛素时，RBF 增加到输注前值的 13%以上（P < 0.05）。在 RBF 变化期间，SAP 或葡萄糖均未发生变化。总之，胰岛素输注模拟了与进餐相关的 RBF 增加，与 SAP 无关，并且持续时间长于血液胰岛素平台期。胰岛素诱导的 RBF 增加仅部分被 L-NAME 阻止。酮洛芬未能阻止胰岛素依赖性 RBF 增加。这两个事实表明，互补的血管舒张剂解释了胰岛素对绵羊肾血流动力学的作用。
