Vlachopoulos Charalambos, Tsekoura Dorothea, Alexopoulos Nikolaos, Panagiotakos Demosthenes, Aznaouridis Konstantinos, Stefanadis Christodoulos
Cardiovascular and Sexual Health Unit, First Department of Cardiology, Athens Medical School, Hippokration Hospital, Athens, Greece.
Am J Hypertens. 2004 Nov;17(11 Pt 1):1040-4. doi: 10.1016/j.amjhyper.2004.06.027.
Endothelial dysfunction is a key early event in the process of atherosclerosis and a risk factor for cardiovascular events. Sildenafil, an effective oral treatment for patients with erectile dysfunction, inhibits cGMP degradation by specific type 5 phosphodiesterase (PDE) inhibition. Sildenafil has been shown to improve vascular function, however, the effect of type 5 PDE inhibition on acute smoking-induced endothelial dysfunction is unknown.
We studied the effect of 50 mg of sildenafil on acute smoking-induced endothelial dysfunction in 14 male smokers according to a randomized, placebo-controlled, cross-over design. Endothelial function was evaluated with flow-mediated dilatation (FMD) of the brachial artery using high-resolution ultrasonography.
Sildenafil abolishes the decrease in FMD of the brachial artery that is induced acutely by smoking (placebo/smoking session: from 4.56% +/- 0.60% to 2.80% +/- 0.43%, sildenafil/smoking session: from 3.83% +/- 0.64% to 4.33% +/- 0.47%, ie, improvement of 51%, P < .05). This was associated with no reversal effect of sildenafil on smoking-induced decrease in resting brachial artery diameter and with a partial reversal of the smoking-induced decrease in hyperemic brachial artery diameter (placebo/smoking session: from 4.68 +/- 0.13 mm to 4.53 +/- 0.15 mm, sildenafil/smoking session: from 4.72 +/- 0.12 mm to 4.64 +/- 0.13 mm, ie, improvement of 1.5%, P < .005).
The present study shows, for the first time, that type 5 PDE inhibition with sildenafil abrogates the smoking-induced acute decrease in FMD of the brachial artery. These findings may have clinical implications given the detrimental consequences of smoking and the strategic role of normal endothelial function.
内皮功能障碍是动脉粥样硬化过程中的一个关键早期事件，也是心血管事件的一个危险因素。西地那非是治疗勃起功能障碍患者的一种有效口服药物，通过特异性抑制5型磷酸二酯酶（PDE）来抑制环磷酸鸟苷（cGMP）降解。西地那非已被证明可改善血管功能，然而，5型PDE抑制对急性吸烟诱导的内皮功能障碍的影响尚不清楚。
我们根据随机、安慰剂对照、交叉设计，研究了50毫克西地那非对14名男性吸烟者急性吸烟诱导的内皮功能障碍的影响。使用高分辨率超声通过肱动脉的血流介导的血管舒张（FMD）来评估内皮功能。
西地那非消除了吸烟急性诱导的肱动脉FMD降低（安慰剂/吸烟时段：从4.56%±0.60%降至2.80%±0.43%，西地那非/吸烟时段：从3.83%±0.64%升至4.33%±0.47%，即改善了51%，P<.05）。这与西地那非对吸烟诱导的静息肱动脉直径降低无逆转作用以及与吸烟诱导的充血肱动脉直径降低的部分逆转相关（安慰剂/吸烟时段：从4.68±0.13毫米降至4.53±0.15毫米，西地那非/吸烟时段：从4.72±0.12毫米降至4.64±0.13毫米，即改善了1.5%，P<.005）。
本研究首次表明，西地那非抑制5型PDE可消除吸烟诱导的肱动脉FMD急性降低。鉴于吸烟的有害后果和正常内皮功能的战略作用，这些发现可能具有临床意义。
