Beenen O H, Mathy M J, Pfaffendorf M, van Zwieten P A
Department of Pharmacotherapy, University of Amsterdam, Academic Medical Centre, The Netherlands.
J Hypertens. 1996 Sep;14(9):1125-30. doi: 10.1097/00004872-199609000-00013.
The aim of this study was to investigate whether diabetes and hypertension cause additive effects in the responses to various vasoconstrictor and vasodilator agents, in isolated perfused kidneys obtained from streptozotocin (STZ)-diabetic Wistar-Kyoto (WKY) rats and from diabetic spontaneously hypertensive rats (SHR).
SHR and WKY rats were administered STZ 55 mg/kg by intravenous injection into a lateral tail vein at age 12 weeks. Eight weeks later the kidneys were isolated and perfused via the left renal artery with a physiological salt solution. Renal perfusion pressure was measured continuously. Concentration response curves were plotted for various vasoconstrictor and vasodilator agents.
Both the diabetic and the hypertensive state were associated with an increased wet kidney weight. The contractile responses of the renal arterial system to phenylephrine (PhE), serotonin (5-HT) and angiotensin II (Ang II) in terms both of the maximal rise in perfusion pressure (mmHg) and of the sensitivity (log EC50) were the same in preparations from diabetic WKY rats and in those from normoglycaemic WKY rats. The maximal contractile responses both to PhE and to Ang II were enhanced in kidneys from SHR compared with those in kidneys from their normotensive controls, whereas simultaneously occurring diabetes impaired this sensitization. After precontraction with 3 x 10(-6) mol/l PhE both endothelium-dependent (methacholine) and endothelium-independent (sodium nitroprusside) vasodilator drugs caused the same vasodilator response in the preparations taken from the four groups of animals.
In isolated perfused kidneys obtained from STZ-diabetic WKY rats and SHR, the isolated diabetic state did not influence the vasoconstriction caused by various agonists. However, the enhanced vascular reactivity in the hypertensive state was blunted by simultaneously occurring diabetes mellitus. Endothelium-dependent and -independent vasorelaxation in this model was not affected neither by the hypertensive nor by the diabetic state.
本研究旨在探讨糖尿病和高血压对链脲佐菌素（STZ）诱导的糖尿病Wistar-Kyoto（WKY）大鼠及糖尿病自发性高血压大鼠（SHR）分离灌注肾对各种血管收缩剂和血管舒张剂反应是否具有叠加效应。
12周龄时，通过尾静脉外侧静脉注射将55mg/kg STZ给予SHR和WKY大鼠。8周后分离肾脏，经左肾动脉用生理盐溶液进行灌注。连续测量肾灌注压。绘制各种血管收缩剂和血管舒张剂的浓度反应曲线。
糖尿病状态和高血压状态均与肾湿重增加有关。糖尿病WKY大鼠制备物中肾动脉系统对去氧肾上腺素（PhE）、5-羟色胺（5-HT）和血管紧张素II（Ang II）的收缩反应，无论是灌注压的最大升高（mmHg）还是敏感性（log EC50），均与血糖正常的WKY大鼠制备物相同。与正常血压对照组的肾脏相比，SHR肾脏对PhE和Ang II的最大收缩反应增强，而同时存在的糖尿病损害了这种敏感性。在用3×10⁻⁶mol/L PhE预收缩后，内皮依赖性（乙酰甲胆碱）和内皮非依赖性（硝普钠）血管舒张药物在四组动物制备物中引起相同的血管舒张反应。
在从STZ诱导的糖尿病WKY大鼠和SHR获得的分离灌注肾中，单纯糖尿病状态不影响各种激动剂引起的血管收缩。然而，同时存在的糖尿病使高血压状态下增强的血管反应性减弱。在该模型中，内皮依赖性和非依赖性血管舒张不受高血压状态或糖尿病状态的影响。
