Kövér G, Tost H, Darvasi A
Department of Physiology, Semmelweis University Medical School, Budapest, Hungary.
Acta Physiol Hung. 1989;74(3-4):229-41.
Studies were performed to determine the mechanism by which the antihypertensive agent clonidine increased urine flow. The response of the kidney has been examined in four combinations. The parameters of renal function have been compared during volume expansion by 1.5-2.0% body weight Ringer solution. In the control animals, volume expansion by 2% body weight, resulted in a slight increase in sodium excretion and urine flow. In 10 anesthetized dogs 1.0 microgram/kg/min of clonidine infused i.v. during 30 minutes (the total amount of clonidine infused was 30 micrograms/kg) decreased the arterial blood pressure from 136 +/- 13 mmHg to 127 +/- 12 mmHg and elevated urine flow from 2.95 +/- 1.65 ml/min to 4.34 +/- 1.77 ml/min while the urine osmolality diminished from 399 +/- 107 mosm/l to 265 +/- 90 mosm/l and the glomerular filtration remained constant. In 5 animals 0.1 microgram/kg/min of clonidine was infused into the left renal artery (this dose is corresponding to the renal fraction of the cardiac output) without any effects in the left kidney. 1.0 microgram/kg/min of clonidine infused directly into the left renal artery produced vasoconstriction in the ipsilateral kidney, decreased the glomerular filtration rate and the urine flow. By contrast in the right kidney the urine flow rose without hemodynamic changes, and the urine osmolality became hypoosmotic compared to the plasma. In ten dogs 1.0 microgram/kg/min of clonidine and 1 mU/kg/min of arginine-vasopressin were infused intravenously. The vasopressin infusion superimposed on the clonidine could not inhibit the increase of the urine excretion, and the fall of the urine osmolality. The results suggest that the clonidine increases the renal medullary blood flow possibly via a direct mechanism, decreases the sympathetic outflow to the kidney and via an indirect pathway, mediated by the renin-angiotensin system. The renal medullary flow increase produces a washout of the medullary osmotic gradient, and the water reabsorption diminishes.
开展了多项研究以确定抗高血压药物可乐定增加尿流量的机制。已对肾脏在四种组合情况下的反应进行了检查。在通过体重1.5 - 2.0%的林格液进行容量扩张期间，对肾功能参数进行了比较。在对照动物中，体重增加2%的容量扩张导致钠排泄和尿流量略有增加。在10只麻醉犬中，静脉输注可乐定1.0微克/千克/分钟，持续30分钟（输注的可乐定总量为30微克/千克），动脉血压从136±13毫米汞柱降至127±12毫米汞柱，尿流量从2.95±1.65毫升/分钟升至4.34±1.77毫升/分钟，而尿渗透压从399±107毫渗量/升降至265±90毫渗量/升，肾小球滤过率保持恒定。在5只动物中，将0.1微克/千克/分钟的可乐定注入左肾动脉（此剂量相当于肾血流量占心输出量的比例），对左肾无任何影响。将1.0微克/千克/分钟的可乐定直接注入左肾动脉会使同侧肾脏血管收缩，降低肾小球滤过率和尿流量。相比之下，右肾的尿流量增加且无血流动力学变化，与血浆相比尿渗透压变为低渗。在10只犬中，静脉输注1.0微克/千克/分钟的可乐定和1毫单位/千克/分钟的精氨酸加压素。叠加在可乐定上的加压素输注并不能抑制尿排泄的增加和尿渗透压的下降。结果表明，可乐定可能通过直接机制增加肾髓质血流量，减少肾交感神经输出，并通过肾素 - 血管紧张素系统介导的间接途径起作用。肾髓质血流量增加导致髓质渗透梯度的冲销，水重吸收减少。
