Involvement of alpha receptors and potassium channels in the mechanisn of action of sildenafil

Modulation of the adrenergic activity and interferring with channels such as potassium channels may affect relaxation and contraction of the corpus cavernosum. Sildenafil is a selective inhibitor of phosphodiesterase 5, proven effective in the treatment of erectile dysfunction. The objective of this study was to test the effect of sildenafil on alpha-receptors modulation and potassium channels. In the present study, it was found that the muscle relaxant effect of sildenafil [1 x 10 [-9] to 1 x 10 [-6] M] on phenylephrineprecontracted rabbit corpus cavernosum strips was not attenuated by NG-nitro-L-arginine [3 x 10 [-5] M]. Cumulative addition of sildenafil [1 x 10 [-9] - 1 x 10 [-6] M] and phentolamine [1 x 10 [-9] to 1 x 10 [-6] M] to the organ bath dose-dependently inhibited electrical field stimulation-induced contraction of rabbit corpus cavernosum and rat anococcygeus muscle with close ED50 values. Sildenafil [1 x 10 [-7] M] also inhibited phenylephrine-induced contraction of rat aortic rings by 39.83 +/- 3.01%. In addition. tetraethylammonium [1 x 10 [-3] M] significantly attenuated the muscle relaxant effect of sildenafil [1 x 10 [-9] - 1 x 10 [-6] M] on phenylephrine-precontracted strips of rabbit corpus cavernosum. sildenafil is capable of producing cavernosal smooth muscle relaxation by an additional mechanism involving alpha-receptors and potassium channel opening

Methanol poisoning in clofibrate treated rats

Small laboratory animals do not exhibit the common symptoms observed in humans poisoned with methanol. This presents a serious problem in the face of attempts trying to study, on experimental basis, the mechanism and treatment of human methanol poisoning. In this study, a suitable experimental animal model for this purpose has been developed. This was made possible by speeding up the rate of conversion of methanol to formate in vivo in rats through the use of clofibrate, a compound that increases hepatic catalase activity, and by concomitantly slowing down the rate of formate disappearance from the body by the use of methotrexate. Methanol administration to such rats resulted in a very marked accumulation of formate in the blood accompanied by the development of severe acidosis. These two changes are the most important characteristics of the human methanol poisoning syndrome. It is hoped that this animal model would be a useful tool in future methanol poisoning studies