Jeremy J Y, Gill J, DuBourg A, Pelat P, Mikhailidis D P
Department of Chemical Pathology and Human Metabolism, Royal Free Hospital and School of Medicine, London, UK.
Int J Impot Res. 1993 Sep;5(3):139-47.
The effect of buflomedil, a vasodilator, on: (a) in vitro prostacyclin (PGI2) synthesis by the rat aorta and penis, human cultured endothelial cells (HUVECs) and human iliac artery, (b) endothelin synthesis by HUVECs and (c) 45Ca2+ uptake by isolated human platelets was investigated. Buflomedil had no effect on PGI2 synthesis by rat aorta, iliac artery or HUVECs (short or long-term incubations). However, buflomedil inhibited noradrenaline- (but not arachidonate- or ionophore A23187-) stimulated PGI2 synthesis. Buflomedil had a weak stimulatory effect on PGI2 synthesis by the isolated rat penis, but this was not inhibited by cholinergic antagonists. Buflomedil (except at supra-therapeutic concentrations) exerted no effect on endothelin release by HUVECS. Buflomedil inhibited 45Ca2+ uptake by human platelets when stimulated with collagen and adrenaline, but not when stimulated with calcium ionophore A23187. These data demonstrate that buflomedil has no deleterious effect on the enzymes that control vascular PGI2 synthesis. The data also adds to the evidence that buflomedil is an alpha-adrenoceptor blocker and has stimulatory effects on penile PGI2 synthesis. Both of these properties may prove useful in the treatment of impotence. The specific inhibition of 45Ca2+ uptake consolidates that buflomedil has some calcium-channel-blocking properties which may explain, at least in part, its vasodilator and antiplatelet properties. Buflomedil may prove beneficial in the treatment of impotence via three mechanisms: (a) stimulation of penile PGI2 synthesis (b) alpha-adrenoceptor blockade and (c) calcium-mobilization-blocking properties.
(a) 大鼠主动脉和阴茎、人培养内皮细胞（HUVECs）及人髂动脉的体外前列环素（PGI2）合成；(b) HUVECs的内皮素合成；(c) 分离的人血小板对45Ca2+的摄取进行了研究。丁咯地尔对大鼠主动脉、髂动脉或HUVECs的PGI2合成（短期或长期孵育）无影响。然而，丁咯地尔抑制去甲肾上腺素（而非花生四烯酸或离子载体A23187）刺激的PGI2合成。丁咯地尔对分离的大鼠阴茎的PGI2合成有微弱的刺激作用，但这不受胆碱能拮抗剂的抑制。丁咯地尔（除超治疗浓度外）对HUVECs释放内皮素无影响。丁咯地尔抑制胶原和肾上腺素刺激时人血小板对45Ca2+的摄取，但不抑制钙离子载体A23187刺激时的摄取。这些数据表明丁咯地尔对控制血管PGI2合成的酶无有害作用。这些数据还进一步证明丁咯地尔是一种α-肾上腺素能受体阻滞剂，对阴茎PGI2合成有刺激作用。这两种特性可能在阳痿治疗中有用。对45Ca2+摄取的特异性抑制证实丁咯地尔具有一些钙通道阻滞特性，这至少可以部分解释其血管扩张和抗血小板特性。丁咯地尔可能通过三种机制在阳痿治疗中发挥有益作用：(a) 刺激阴茎PGI2合成；(b) α-肾上腺素能受体阻滞；(c) 钙动员阻滞特性。
