Kahn S A, Gulmi F A, Chou S Y, Mooppan U M, Kim H
Department of Urology, The Brookdale University Hospital and Medical Center, Brooklyn, New York 11212, USA.
J Urol. 1997 May;157(5):1957-62.
In unilateral ureteral obstruction (UUO) vasoconstriction occurs both during and after release of UUO. ET-1, an endogenous peptide, causes marked vasoconstriction mediated by an increase in cytosolic calcium. We measured renal output of endothelin-1 (ET-1) in dogs with UUO and examined if the renal vasoconstriction that persisted after release of UUO could be reversed by a calcium antagonist, verapamil.
Hemodynamic and clearance experiments were performed in anesthetized mongrel dogs in three groups. Group I consisted of 9 dogs with sham-operation. Group 2 consisted of 7 dogs in whom ureteral obstruction was released 1.9 hours after UUO. Group 3 consisted of 5 dogs in whom verapamil was infused into the renal artery at two doses (5 and 10 microg./min., respectively) after release of UUO of 19-hour duration. ET-1 concentrations (measured by radioimmunoassay) were determined for renal venous and arterial plasma.
In Group 1 renal venous plasma ET-1 level was 16.7 +/- 2.2, significantly lowered than 22.8 +/- 3.2 pg./ml. in arterial plasma, indicating a net clearance of ET-1. In Group 2 and 3, renal venous plasma ET-1 levels (28.2 +/- 5.2 and 27.2 +/- 2.4 pg./ml., respectively) were significantly greater than those in arterial plasma (24.2 +/- 5.7 and 17.4 +/- 0.8 pg./ml., respectively), indicating a net output of ET-1 in the kidney, In addition, renal vasoconstriction occurred in Groups 2 and 3 as indicated by significantly lower renal blood flow and GFR than those in Group 1. In Group 3, intrarenal infusion of verapamil at two doses did not change arterial pressure but caused an ipsilateral, significant increase in RBF (from 132 +/- 4 17 to 1.84 +/- 19 and 180 +/- 16 ml./min., respectively) and dose-dependent increases in GFR (from 12 +/- 2 to 25 +/- 3 and 38 +/- 7 ml./min., respectively), associated with a profound dose-dependent ipsilateral diuresis and natriuresis.
Profound renal vasoconstriction in UUO was associated with an increase in renal production of ET-1, possibly contributing to renal vasoconstriction, and was reversed by intrarenal infusion of verapamil.
在单侧输尿管梗阻（UUO）过程中及梗阻解除后均会发生血管收缩。内皮素-1（ET-1）是一种内源性肽，可通过增加细胞内钙介导显著的血管收缩。我们测定了UUO犬的内皮素-1（ET-1）肾输出量，并研究了UUO解除后持续存在的肾血管收缩是否可被钙拮抗剂维拉帕米逆转。
对三组麻醉的杂种犬进行血流动力学和清除率实验。第一组由9只接受假手术的犬组成。第二组由7只在UUO后1.9小时解除输尿管梗阻的犬组成。第三组由5只在持续19小时的UUO解除后以两种剂量（分别为5和10微克/分钟）向肾动脉输注维拉帕米的犬组成。通过放射免疫测定法测定肾静脉和动脉血浆中的ET-1浓度。
在第一组中，肾静脉血浆ET-1水平为16.7±2.2，明显低于动脉血浆中的22.8±3.2皮克/毫升，表明ET-1有净清除。在第二组和第三组中，肾静脉血浆ET-1水平（分别为28.2±5.2和27.2±2.4皮克/毫升）明显高于动脉血浆中的水平（分别为24.2±5.7和17.4±0.8皮克/毫升），表明肾脏中有ET-1的净输出。此外，第二组和第三组出现了肾血管收缩，表现为肾血流量和肾小球滤过率明显低于第一组。在第三组中，以两种剂量向肾内输注维拉帕米并未改变动脉血压，但导致同侧肾血流量显著增加（分别从132±417增加到1.84±19和180±16毫升/分钟），肾小球滤过率呈剂量依赖性增加（分别从12±2增加到25±3和38±7毫升/分钟），同时伴有剂量依赖性的同侧显著利尿和利钠。
UUO时严重的肾血管收缩与肾脏ET-1生成增加有关，这可能是肾血管收缩的原因，并且通过向肾内输注维拉帕米可使其逆转。
