Stanke F, Devillier P, Bréant D, Chavanon O, Sessa C, Bricca G, Bessard G
Laboratory of Pharmacology, PCEBM, Faculté de Médecine, La Tronche, France.
Br J Clin Pharmacol. 1998 Dec;46(6):571-5. doi: 10.1046/j.1365-2125.1998.00820.x.
Frusemide is widely used in the treatment of acute pulmonary oedema, chronic congestive heart failure and, to a lesser degree, in the treatment of hypertension. Evidence suggests that frusenuide exerts an anti-vasoconstrictor effect independent of its diuretic properties. Since angiotensin II is a highly potent vasoconstrictor involved in the pathophysiology of these diseases, we have investigated the effect of frusemide on the contraction elicited by angiotensin II on human internal mammary artery (IMA) and saphenous vein (SV).
Rings of IMA and SV were suspended for isometric tension recording in organ baths. Concentration-response curves to angiotensin II were performed in the absence (control) or in the presence of frusemide (10(-6) to 10(-3) M). In addition, the effect of frusemide was evaluated after cyclooxygenase inhibition by indomethacin (10(-6) M) and was compared with those of the other loop diuretic bumetanide (10(-4) M).
Frusemide induced a concentration-dependent decrease of the contraction elicited by angiotensin II on IMA and SV. On both vessels, the inhibitory effect on the maximal contraction to angiotensin II was significant with concentrations of frusemide from 10(-5) to 10(-3) M. Angiotensin II potency (pD2) was only reduced by 10(-3) M frusemide. The effect of frusemide was not altered in the presence of indomethacin. Bumetanide was less potent than frusemide in inhibiting angiotensin II-induced contractions in both IMA and SV.
Frusemide, at concentrations in the therapeutic range (10(-5) M), inhibits angiotensin II-induced contraction on human isolated IMA and SV. This inhibitory effect is cyclooxygenase independent and appears mediated, at least in part, by inhibition of Na+/K+/2Cl- symport. Reduction in the vasoconstrictor effect of angiotensin 1 may be involved in the therapeutic efficacy of frusemide.
速尿广泛用于治疗急性肺水肿、慢性充血性心力衰竭，在较小程度上也用于治疗高血压。有证据表明，速尿发挥抗血管收缩作用与其利尿特性无关。由于血管紧张素II是参与这些疾病病理生理过程的强效血管收缩剂，我们研究了速尿对血管紧张素II引起的人乳内动脉（IMA）和大隐静脉（SV）收缩的影响。
将IMA和SV的血管环悬挂在器官浴槽中进行等长张力记录。在不存在（对照）或存在速尿（10⁻⁶至10⁻³M）的情况下绘制血管紧张素II的浓度-反应曲线。此外，在通过吲哚美辛（10⁻⁶M）抑制环氧化酶后评估速尿的作用，并与另一种袢利尿剂布美他尼（10⁻⁴M）的作用进行比较。
速尿引起血管紧张素II对IMA和SV收缩的浓度依赖性降低。在两条血管上，速尿浓度为10⁻⁵至10⁻³M时对血管紧张素II最大收缩的抑制作用显著。血管紧张素II的效价（pD2）仅在10⁻³M速尿时降低。在吲哚美辛存在的情况下，速尿的作用未改变。在抑制IMA和SV中血管紧张素II诱导的收缩方面，布美他尼的效力低于速尿。
治疗范围内浓度（10⁻⁵M）的速尿可抑制血管紧张素II对人离体IMA和SV的收缩。这种抑制作用不依赖环氧化酶，至少部分似乎是由对Na⁺/K⁺/2Cl⁻同向转运体的抑制介导的。血管紧张素I血管收缩作用的降低可能与速尿的治疗效果有关。
