Department of Physiology, Medical College of Georgia at Augusta University , Augusta, Georgia.
Department of Cellular Biology & Anatomy, Medical College of Georgia at Augusta University , Augusta, Georgia.
Am J Physiol Renal Physiol. 2018 Jan 1;314(1):F81-F88. doi: 10.1152/ajprenal.00374.2017. Epub 2017 Sep 27.
Hyperinsulinemia has been hypothesized to cause hypertension in obesity, type 2 diabetes, and metabolic syndrome through a renal mechanism. However, it has been challenging to isolate renal mechanisms in chronic experimental models due, in part, to technical difficulties. In this study, we tested the hypothesis that a renal mechanism underlies insulin hypertension. We developed a novel technique to permit continuous insulin infusion through the renal artery in conscious rats for 7 days. Mean arterial pressure increased by ~10 mmHg in rats that were infused intravenously (IV) with insulin and glucose. Renal artery doses were 20% of the intravenous doses and did not raise systemic insulin levels or cause differences in blood glucose. The increase in blood pressure was not different from the IV group. Mean arterial pressure did not change in vehicle-infused rats, and there were no differences in renal injury scoring due to the renal artery catheter. Glomerular filtration rate, plasma renin activity, and urinary sodium excretion did not differ between groups at baseline and did not change significantly with insulin infusion. Thus, by developing a novel approach for chronic, continuous renal artery insulin infusion, we provided new evidence that insulin causes hypertension in rats through actions initiated within the kidney.
高胰岛素血症被认为是通过肾脏机制导致肥胖、2 型糖尿病和代谢综合征患者发生高血压的原因。然而，由于技术上的困难，在慢性实验模型中分离肾脏机制一直具有挑战性。在这项研究中，我们检验了胰岛素引起高血压的肾脏机制假说。我们开发了一种新的技术，可在清醒大鼠中通过肾动脉持续输注胰岛素 7 天。静脉输注胰岛素和葡萄糖的大鼠平均动脉压升高约 10mmHg。肾动脉剂量为静脉剂量的 20%，不会升高全身胰岛素水平或导致血糖差异。血压升高与静脉组无差异。输注载体的大鼠平均动脉压没有变化，并且由于肾动脉导管，肾脏损伤评分没有差异。肾小球滤过率、血浆肾素活性和尿钠排泄在基线时在各组之间没有差异，并且随着胰岛素输注没有显著变化。因此，通过开发一种用于慢性、持续肾动脉胰岛素输注的新方法，我们提供了新的证据，证明胰岛素通过肾脏内的作用导致大鼠发生高血压。
