thromboxane-a2 and Erectile-Dysfunction

To assess the effect of sildenafil on superoxide formation and p47(phox) (the active subunit of NADPH oxidase) expression in cultured corpus cavernosal smooth muscle cells (CVSMCs).. CVSMCs derived from rabbit penis were incubated with U46619 (thromboxane A2 analogue) with or without sildenafil for 1 or 16 h at 37 degrees C. Superoxide dismutase-inhibitable superoxide formation was assessed using the reduction of ferricytochrome c measured spectrophotometrically, and gp47(phox) assessed using Western blot analysis. The role of NAD[P]H oxidase and cGMP was further studied by using specific inhibitors of each.. Superoxide formation was significantly greater in cells incubated with U46619 after 1 and 16 h incubation than in controls, an effect blocked by NADP(H) oxidase inhibitors. These effects of U46619 were inhibited by sildenafil (1 and 10 nmol/L), which in turn were negated by the guanylyl cyclase inhibitor, ODQ; 10 nmol/L sildenafil inhibited p47phox expression induced by U46619.. Sildenafil is a potent inhibitor of superoxide formation in CVSMCs. This effect is mediated through the inhibition of PDE-5 which in turn augments the inhibitory action of the NO-cGMP axis on NAD[P]H oxidase expression and activity. This mechanism constitutes a new pharmacological action of sildenafil, consolidates the potential role of superoxide in ED, and indicates that thromboxane A(2) may be an important mediator of intrapenile oxidative stress.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Animals; Erectile Dysfunction; Male; Muscle, Smooth, Vascular; NADPH Oxidases; Penis; Piperazines; Purines; Rats; Sildenafil Citrate; Sulfones; Superoxides; Thromboxane A2; Vasoconstrictor Agents

The release of mediator substances of the arachidonic acid cascade is closely related to the functional state of the endothelium. A significant lower prostacyclin/thromboxane A2 ratio in penile plasma of organogenic impotent patients in comparison to patients with psychogenic erectile dysfunction has been described in the literature. We observed the time-related liberation of prostacyclin, thromboxane A2 and the vasoactive peptide endothelin for 16 minutes of a drug-induced erection. We compared kinetics of patients with penile deviation and transsexualism, to patients suffering from severe organogenic impotence. We assessed the usefulness of the prostacyclin-to-thromboxane A2 ratio as a possible indicator of corporal degeneration. An animal model has been created to observe differences between rabbits under 100 days of standard diet alimentation, rabbits under cholesterol enriched diet and rabbits with hereditary hyperlipidemia type II A. Hyperlipidemia is suspected to be one possible factor causing organogenic impotence. Enzyme-immuno-assays were used for the determination of all substances. The systemic prostacyclin-to-thromboxane A2 ratio differed significantly between control rabbits and rabbits with hyperlipidemia. Prostacyclin, thromboxane A2 and endothelin in corpus cavernosum plasma showed a typical profile during spontaneous and drug-induced erection. A significant difference between groups of patients suffering from organogenic or psychogenic impotence could not be found. The value of the determination of the studied substances in differential diagnosis seems to be dubious.

Topics: Alprostadil; Animals; Endothelins; Epoprostenol; Erectile Dysfunction; Humans; Kinetics; Male; Penile Diseases; Penile Erection; Penis; Prostaglandins; Rabbits; Thromboxane A2; Transsexualism

It has been suggested that penile hypercoagulability predisposes to aging penile vascular changes and impotence, and that elevated thromboxane A2 during erection may contribute to hypercoagulability and atherosclerosis. Since the ratio of the prostacyclin concentration to the thromboxane A2 concentration is constantly maintained in normal hemostatic responses, an imbalance between thromboxane A2 and prostacyclin may be a factor to initiate vascular diseases and decrease blood flow. We assess the usefulness of the prostacyclin-to-thromboxane A2 ratio in penile blood during erection for diagnosis of arteriogenic impotence. The ratio in the arteriogenic impotence group was significantly lower (p less than 0.01) than in the psychogenic and venogenic impotence groups. Therefore, the prostacyclin-to-thromboxane A2 ratio seems to be useful to diagnose arteriogenic impotence.

Topics: Adult; Epoprostenol; Erectile Dysfunction; Humans; Male; Penile Erection; Penis; Thromboxane A2; Vascular Diseases

Topics: Aging; Erectile Dysfunction; Humans; Male; Penis; Thromboxane A2; Thromboxane-A Synthase

Topics: Aging; Animals; Blood Platelets; Erectile Dysfunction; Male; Papio; Penis; Platelet Aggregation; Thromboxane A2