Ried Michael, Neu Reiner, Lehle Karla, Großer Christian, Szöke Tamas, Lang Gunter, Hofmann Hans-Stefan, Hoenicka Markus
Department of Thoracic Surgery, University Medical Center Regensburg, Regensburg, Germany.
Department of Cardiothoracic Surgery, University Medical Center Regensburg, Regensburg, Germany.
Interact Cardiovasc Thorac Surg. 2017 Aug 1;25(2):254-259. doi: 10.1093/icvts/ivx108.
Pulmonary arterial hypertension is characterized by pulmonary vascular proliferation and remodelling, leading to a progressive increase in pulmonary arterial resistance. Vasodilator properties of 3 different phosphodiesterase (PDE)-5 inhibitors alone and in combination with an endothelin (ET) receptor antagonist were compared in an ex vivo model.
Segments of human pulmonary arteries (PAs) and pulmonary veins (PVs) were harvested from lobectomy specimens. Contractile forces were determined in an organ bath. Vessels were constricted with norepinephrine (NE) to determine the effects of sildenafil, tadalafil and vardenafil and with ET-1 to assess the effects of bosentan.
All 3 PDE-5 inhibitors had no relevant effect on the basal tone of the vessels. Both sildenafil and vardenafil significantly (P < 0.0001) reduced the responses of the vessels to NE, whereas tadalafil was effective only in PA (P = 0.0009) but not in PV (P = 0.097). Sildenafil relaxed NE-preconstricted PV (P < 0.0001) but not PA (P = 0.143). Both tadalafil and vardenafil relaxed PA and PV significantly. Vardenafil appears to be the most potent of the PDE-5 inhibitors tested. Furthermore, we analysed the combination of bosentan and vardenafil in PA. Bosentan and vardenafil reduced ET-1 and NE induced vasoconstriction stronger than vardenafil alone (P ≤ 0.049).
Vardenafil caused the most consistent antihypertensive response in this ex vivo model. However, ET receptor antagonism appears to be an even more potent mechanism. A combination therapy using vardenafil and bosentan turned out to be an effective combination to lower vessel tension in PA.
肺动脉高压的特征是肺血管增殖和重塑，导致肺动脉阻力逐渐增加。在体外模型中比较了3种不同磷酸二酯酶（PDE）-5抑制剂单独使用以及与内皮素（ET）受体拮抗剂联合使用时的血管舒张特性。
从肺叶切除标本中获取人肺动脉（PA）和肺静脉（PV）段。在器官浴中测定收缩力。用去甲肾上腺素（NE）使血管收缩以确定西地那非、他达拉非和伐地那非的作用，并用ET-1使血管收缩以评估波生坦的作用。
所有3种PDE-5抑制剂对血管的基础张力均无显著影响。西地那非和伐地那非均显著（P<0.0001）降低了血管对NE的反应，而他达拉非仅对PA有效（P=0.0009），对PV无效（P=0.097）。西地那非使NE预收缩的PV舒张（P<0.0001），但对PA无效（P=0.143）。他达拉非和伐地那非均使PA和PV显著舒张。伐地那非似乎是所测试的PDE-5抑制剂中最有效的。此外，我们分析了波生坦和伐地那非在PA中的联合作用。波生坦和伐地那非比单独使用伐地那非更能有效降低ET-1和NE诱导的血管收缩（P≤0.049）。
在该体外模型中，伐地那非引起的降压反应最为一致。然而，ET受体拮抗作用似乎是一种更有效的机制。使用伐地那非和波生坦的联合治疗被证明是降低PA血管张力的有效组合。
