Ovcharenko Elena, Abassi Zaid, Rubinstein Irith, Kaballa Aviva, Hoffman Aaron, Winaver Joseph
Department of Physiology and Biophysics, Faculty of Medicine, Technion, IIT, PO Box 9649, Haifa, 31096, Israel.
Nephrol Dial Transplant. 2006 May;21(5):1205-11. doi: 10.1093/ndt/gfk049. Epub 2006 Jan 5.
Urotensin II (U-II) and its receptor GPR-14 are expressed in the kidney and the cardiovascular system of various mammalian species. Recent studies suggested that the U-II/GPR-14 system is upregulated in patients with congestive heart failure (CHF). However, the involvement of the peptide in the alterations of renal function in CHF remains unknown.
The effects of incremental doses (1.0-100.0 nmol/kg) of human U-II (hU-II) on renal haemodynamic and clearance parameters were assessed in rats with an aorto-caval fistula, an experimental model of CHF, and sham controls. Additionally, the effects of pre-treatment with the nitric oxide (NO) synthase blocker, nitro-L-arginine methyl ester (L-NAME), and the cyclooxygenase inhibitor, indomethacin, on the renal haemodynamic response to hU-II were studied in CHF rats.
hU-II caused a decrease in mean arterial pressure in control and CHF rats. In controls, hU-II did not alter renal blood flow (RBF), and caused a minimal decrease (-12.5%) in renal vascular resistance (RVR). However, in CHF rats, the peptide induced a marked increase in RBF (+28%) and a decrease in RVR (-21.5%). These effects were attenuated by L-NAME, but not by indomethacin. Furthermore, hU-II caused a significant increase (+29%) in glomerular filtration rate (GFR) in CHF rats, whereas GFR tended to decrease in controls. Sodium excretion was not altered in control or in CHF rats in response to hU-II.
hU-II exerts an NO-dependent renal vasodilatation that is more pronounced in rats with CHF. The data further suggest that the U-II/GPR-14 system may be involved in the regulation of renal haemodynamics in CHF.
尾加压素 II（U-II）及其受体 GPR-14 在多种哺乳动物的肾脏和心血管系统中表达。最近的研究表明，充血性心力衰竭（CHF）患者的 U-II/GPR-14 系统上调。然而，该肽在 CHF 患者肾功能改变中的作用尚不清楚。
在主动脉 - 腔静脉瘘大鼠（一种 CHF 实验模型）和假手术对照组中，评估递增剂量（1.0 - 100.0 nmol/kg）的人 U-II（hU-II）对肾脏血流动力学和清除参数的影响。此外，在 CHF 大鼠中研究了用一氧化氮（NO）合酶阻滞剂硝基 - L - 精氨酸甲酯（L-NAME）和环氧化酶抑制剂吲哚美辛预处理对 hU-II 肾脏血流动力学反应的影响。
hU-II 使对照组和 CHF 大鼠的平均动脉压降低。在对照组中，hU-II 不改变肾血流量（RBF），并使肾血管阻力（RVR）略有降低（-12.5%）。然而，在 CHF 大鼠中，该肽诱导 RBF 显著增加（+28%）和 RVR 降低（-21.5%）。这些作用被 L-NAME 减弱，但不被吲哚美辛减弱。此外，hU-II 使 CHF 大鼠的肾小球滤过率（GFR）显著增加（+29%），而对照组中的 GFR 有下降趋势。hU-II 对对照组或 CHF 大鼠的钠排泄无影响。
hU-II 发挥 NO 依赖性肾血管舒张作用，在 CHF 大鼠中更明显。数据进一步表明，U-II/GPR-14 系统可能参与 CHF 中肾脏血流动力学的调节。
Zotero 插件