Prostanoid production in rabbit corpus cavernosum .1. Regulation by oxygen tension

Purpose: To investigate the effects of oxygen tension on prostanoid synthesis in rabbit penile corpus cavernosum tissue (RCC) in organ culture. Materials and Methods: Strips of rabbit corpus cavernosum were incubated in organ culture media under varying oxygen conditions (0%, 12% and 21% oxygen), in the presence or absence of acetylcholine and arachidonate stimulation, Prostanoids were measured in collected media by radioimmunoassay. Prostaglandin H synthase (PGHS) protein levels and mRNA PGHS expression were measured under both 0% and 21% oxygen conditions, Results: Basal and acetylcholine-stimulated PGI(2) release was progressively diminished as a function of diminishing oxygen tension (pO(2) from similar to 165 to 25 mm.Hg). The basal and stimulated production of other prostanoids, thromboxane A(2), PGF(2 alpha) and PGE(2), was also significantly inhibited under 0% oxygen (similar to 25 mm.Hg) conditions. However, incubation under 0% oxygen did not alter PGHS protein levels nor mRNA PGHS expression, Cavernosal strips incubated under 0% oxygen but supplemented with exogenous arachidonate (10 mu M.) maintained significantly lower PGI(2) production than tissues exposed to 21% oxygen (similar to 165 mm.Hg). Conclusions: These data demonstrate that oxygen tension regulates prostaglandin production in corporal tissue. The reduction in prostanoid production during hypoxia can be attributed to inhibition of PGHS activity rather than the expression of the enzyme. In view of the role of PGI(2) as an inhibitor of platelet aggregation and white cell-endothelial adhesion, our findings may provide mechanistic insight into the alteration in corporal blood homeostasis during ischemic-hypoxic priapism.