A Review of the Pathophysiology and Novel Treatments for Erectile Dysfunction

Erectile dysfunction (ED) affects up to 50% of men between the ages of 40 and 70. Treatment with PDE-5 inhibitors is effective in the majority of men with ED. However, PDE-5 inhibitors are not effective when levels of nitric oxide (NO), the principle mediator of erection, are low. The pharmacologic actions of three new potential treatments for ED are discussed in this paper: (1) sGC stimulators/activators, (2) Rho-kinase inhibitors, and (3) sodium nitrite

Analysis of Responses to Leukotriene D 4 in the Pulmonary Vascular Bed

SUMMARY. Pulmonary vascular responses to leukotriene D 4 were investigated in the intact-chest animal under conditions of controlled pulmonary blood flow. Intralobar injections of leukotriene D 4 in the sheep caused dose-dependent increases in' lobar arterial and small vein pressures without influencing left atrial or systemic arterial pressure. Leukotriene D 4 was very potent in increasing pulmonary vascular resistance in the sheep, with activity similar to that of U-46619, a thromboxane A 2 mimic. Pulmonary vascular responses to leukotriene D 4 in the sheep were similar when the lung was ventilated and when lobar ventilation was arrested. Responses to leukotriene D 4 were similar when the lung was perfused with blood or with dextran. Pulmonary vascular responses to leukotriene D 4 but not U-46619 in the sheep were reduced by inhibitors of cyclooxygenase and thromboxane synthesis. In contrast, leukotriene D 4 had modest pressor activity in the pulmonary vascular bed of the cat whereas U-46619 had marked activity in this species. Responses to leukotriene D 4 in the cat were not altered by cyclooxygenase inhibitors. It is concluded that leukotriene D 4 has marked pulmonary vasoconstrictor activity in the sheep, increasing pulmonary vascular resistance by constricting intrapulmonary veins and upstream segments. In this species, responses to leukotriene D 4 were independent of changes in ventilation or interaction with formed elements but were dependent on the formation of cyclooxygenase products including thromboxane A2. However, in the cat, leukotriene D 4 had very modest pressor activity, and this activity was not dependent on the integrity of the cyclooxygenase pathway. These data suggest considerable species difference in responses to leukotriene D 4 , a major component of the slow-reacting substance of anaphylaxis, in the pulmonary vascular bed. (Circ Res 55: 707-717, 1984