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德国研究发现伟哥可治疗舒张性心力衰竭

2011/12/27 来源:新浪科技
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研究发现伟哥能够为心脏患者带去福音。这种药物能够让过于僵硬的心室壁变得更具弹性。研究中,科学家揭示出伟哥如何让舒张性心力衰竭患者受益。这种心脏病患者的主心室出现异常僵硬,无法充分泵血,导致血液进入肺部,引发呼吸困难。

科学家研制伟哥之初的目的就是用于治疗心脏病

德国科学家经研究发现,伟哥能够以一种令人吃惊的方式帮助心脏恢复——降低心肌的僵硬度,从而治疗舒张性心力衰竭。这种药物研制之初的目的就是用于治疗心脏病,但更著名的功效却是提高性能力这种堪称意外之喜的“副作用”。

研究发现伟哥能够为心脏患者带去福音。这种药物能够让过于僵硬的心室壁变得更具弹性。研究中,科学家揭示出伟哥如何让舒张性心力衰竭患者受益。这种心脏病患者的主心室出现异常僵硬,无法充分泵血,导致血液进入肺部,引发呼吸困难。

科学家发现伟哥能够激活一种促使心肌细胞中一种蛋白“放松”的酶。在服用伟哥几分钟后,科学家在患有舒张性心力衰竭的狗身上发现这种效用。研究领导人、德国波鸿鲁尔大学的沃尔夫冈-林克教授表示:“我们第一次找到可用于治疗动物的疗法,我们希望能够在人类患者身上复制这种成功。”

伟哥对血管产生类似影响,这也就是为什么这种药物研制之初的目的用于治疗高血压和心脏病。伟哥中的有效成分西地那非能够抑制与血流控制机制有关的酶。然而,这种酶在身体不同部位存在微小差异。研制伟哥的英国科学家最初陷入失望之中,因为这种药物无法有效治疗高血压患者。但令他们感到吃惊的是,伟哥却对阳痿患者产生神奇疗效。

伟哥能够有效抑制阴茎中的磷酸二酯酶,增加流入阴茎的血量。林克教授的研究小组发现,伟哥能够对心脏细胞中同样的酶产生抑制作用,让心肌中的肌联蛋白变得更具弹性。林克说:“肌联蛋白分子与橡皮筋类似,对心壁的硬度产生决定性作用。”研究发现刊登在《Circulation》杂志上。据统计,有近一半心力衰竭急诊患者存在心脏舒张问题。舒张性心力衰竭影响半个心动周期的心脏舒张,此时心室完成收缩,重新充满血。

 

Sildenafil and B-Type Natriuretic Peptide Acutely Phosphorylate Titin and Improve Diastolic Distensibility In Vivo

Kalkidan Bishu, MD; Nazha Hamdani, PhD; Selma F. Mohammed, MBBS; Martina Kruger, PhD; Tomohito Ohtani, MD, PhD; Ozgur Ogut, PhD; Frank V. Brozovich, MD, PhD; John C. Burnett Jr, MD; Wolfgang A. Linke, PhD; Margaret M. Redfield, MD

Background—In vitro studies suggest that phosphorylation of titin reduces myocyte/myofiber stiffness. Titin can be phosphorylated by cGMP-activated protein kinase. Intracellular cGMP production is stimulated by B-type natriuretic peptide (BNP) and degraded by phosphodiesterases, including phosphodiesterase-5A. We hypothesized that a phosphodiesterase-5A inhibitor (sildenafil) alone or in combination with BNP would increase left ventricular diastolic distensibility by phosphorylating titin.

Methods and Results—Eight elderly dogs with experimental hypertension and 4 young normal dogs underwent measurement of the end-diastolic pressure-volume relationship during caval occlusion at baseline, after sildenafil, and BNP infusion. To assess diastolic distensibility independently of load/extrinsic forces, the end-diastolic volume at a common end-diastolic pressure on the sequential end-diastolic pressure-volume relationships was measured (left ventricular capacitance). In a separate group of dogs (n=7 old hypertensive and 7 young normal), serial full-thickness left ventricular biopsies were harvested from the beating heart during identical infusions to measure myofilament protein phosphorylation. Plasma cGMP increased with sildenafil and further with BNP (7.31±2.37 to 26.9±10.3 to 70.3±8.1 pmol/mL; P<0.001). Left ventricular diastolic capacitance increased with sildenafil and further with BNP (51.4±16.9 to 53.7±16.8 to 60.0±19.4 mL; P<0.001). Changes were similar in old hypertensive and young normal dogs. There were no effects on phosphorylation of troponin I, troponin T, phospholamban, or myosin light chain-1 or -2. Titin phosphorylation increased with sildenafil and BNP, whereas titin-based cardiomyocyte stiffness decreased.

Conclusion—Short-term cGMP-enhancing treatment with sildenafil and BNP improves left ventricular diastolic distensibility in vivo, in part by phosphorylating titin.

文献链接:http://circ.ahajournals.org/content/124/25/2882.abstract?sid=a08db160-9f57-42d0-ba34-047096177ca7

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