Effect of buflomedil on in vitro prostacyclin and endothelin synthesis by vascular (rat and human) and penile (rat) tissue and calcium uptake by isolated human platelets.

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.