Pickkers Peter, Russel Frans G M, Thien Theo, Hughes Alun D, Smits Paul
Department of Intensive Care Medicine (519), University Medical Center St. Radboud, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
Eur J Pharmacol. 2003 Apr 18;466(3):281-7. doi: 10.1016/s0014-2999(03)01536-x.
Besides their diuretic action, loop diuretics may induce a rapid vasodilator effect that contribute to their short-term therapeutic properties. We examined the effects of furosemide (10(-6)-10(-3) mol l(-1)) in comparison with bumetanide (10(-6)-10(-4) mol l(-1)) on isolated resistance arteries from rat and guinea pig mesentery and human subcutaneous fat, and investigated the mechanism of the acute direct vasorelaxant action on an isometric microvascular myograph. Both loop diuretics induced concentration-dependent relaxation of resistance vessels irrespective of membrane potential. The maximal effect of furosemide was greatest in rat and least in human arteries. Both diuretics caused a rightward shift in the concentration-response curve to extracellular Ca(2+). Incubation with indomethacin (2 x 10(-5) mol l(-1)) or mechanical removal of the endothelium did not inhibit the loop diuretic-induced relaxation. At high concentrations (10(-4)-10(-3) mol l(-1)) loop diuretics exert only weak direct relaxant effects on isolated human subcutaneous resistance arteries compared to the vasorelaxant effects in rat and guinea pig mesenteric vessels.
除了其利尿作用外,袢利尿剂可能会诱发快速的血管舒张作用,这有助于其发挥短期治疗特性。我们研究了呋塞米(10⁻⁶ - 10⁻³ mol·l⁻¹)与布美他尼(10⁻⁶ - 10⁻⁴ mol·l⁻¹)对大鼠和豚鼠肠系膜以及人体皮下脂肪分离的阻力动脉的影响,并在等长微血管肌动描记器上研究了急性直接血管舒张作用的机制。两种袢利尿剂均能引起阻力血管的浓度依赖性舒张,且与膜电位无关。呋塞米的最大效应在大鼠中最大,在人体动脉中最小。两种利尿剂均使细胞外钙的浓度 - 反应曲线向右移动。用吲哚美辛(2×10⁻⁵ mol·l⁻¹)孵育或机械去除内皮均不抑制袢利尿剂诱导的舒张。与在大鼠和豚鼠肠系膜血管中的血管舒张作用相比,在高浓度(10⁻⁴ - 10⁻³ mol·l⁻¹)时,袢利尿剂对分离的人体皮下阻力动脉仅产生微弱的直接舒张作用。