Department of Pharmacology and Toxicology, School of Medicine, University Complutense of Madrid, 28040 Madrid, Spain; Ciber Enfermedades Respiratorias (CIBERES), 28029 Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), 28009 Madrid, Spain.
Ciber Enfermedades Respiratorias (CIBERES), 28029 Madrid, Spain; Department of Critical Care, Hospital Universitario de Getafe, 28905 Madrid, Spain.
Vascul Pharmacol. 2024 Jun;155:107371. doi: 10.1016/j.vph.2024.107371. Epub 2024 Apr 8.
An effective pulmonary hypertension (PH) treatment should combine antiproliferative and vasodilator effects. We characterized a wide-range of drugs comparing their anti-proliferative vs vasodilator effects in human and rat pulmonary artery smooth muscle cells (PASMC). Key findings: 1) Approved PH drugs (PDE5 inhibitors, sGC stimulators and PGI agonists) are preferential vasodilators. 2) cGMP stimulators were more effective in cells derived from hypertensive rats. 3) Nifedipine acted equally as vasodilator and antiproliferative. 4) quercetin and imatinib were potent dual vasodilator/antiproliferative drugs. 5) Tacrolimus and levosimendan lacked antiproliferative effects. 6) Forskolin, pinacidil and hydroxyfasudil were more effective as antiproliferative in human cells.
一种有效的肺动脉高压（PH）治疗方法应同时具有抗增殖和血管舒张作用。我们对多种药物进行了特征描述，比较了它们在人及大鼠肺动脉平滑肌细胞（PASMC）中的抗增殖作用与血管舒张作用。主要发现：1）已批准的 PH 药物（PDE5 抑制剂、sGC 刺激剂和 PGI 激动剂）为优先的血管舒张剂。2）cGMP 刺激剂在源自高血压大鼠的细胞中更有效。3）硝苯地平作为血管舒张剂和抗增殖剂同样有效。4）槲皮素和伊马替尼是有效的双重血管舒张/抗增殖药物。5）他克莫司和左西孟旦缺乏抗增殖作用。6）福司可林、烟碱及羟甲戊二酰基辅酶 A（HMG-CoA）还原酶抑制剂更有效地抑制人细胞的增殖。
