PROSTANOID PRODUCTION IN RABBIT CORPUS CAVERNOSUM .1. REGULATION BY OXYGEN-TENSION

Purpose: To investigate the effects of oxygen tension on prostanoid sy nthesis in rabbit penile corpus cavernosum tissue (RCC) in organ cultu re. Materials and Methods: Strips of rabbit corpus cavernosum were inc ubated in organ culture media under varying oxygen conditions (0%, 12% and 21% oxygen), in the presence or absence of acetylcholine and arac hidonate stimulation, Prostanoids were measured in collected media by radioimmunoassay. Prostaglandin H synthase (PGHS) protein levels and m RNA PGHS expression were measured under both 0% and 21% oxygen conditi ons, Results: Basal and acetylcholine-stimulated PGI(2) release was pr ogressively diminished as a function of diminishing oxygen tension (pO (2) from similar to 165 to 25 mm.Hg). The basal and stimulated product ion of other prostanoids, thromboxane A(2), PGF(2 alpha) and PGE(2), w as also significantly inhibited under 0% oxygen (similar to 25 mm.Hg) conditions. However, incubation under 0% oxygen did not alter PGHS pro tein levels nor mRNA PGHS expression, Cavernosal strips incubated unde r 0% oxygen but supplemented with exogenous arachidonate (10 mu M.) ma intained significantly lower PGI(2) production than tissues exposed to 21% oxygen (similar to 165 mm.Hg). Conclusions: These data demonstrat e that oxygen tension regulates prostaglandin production in corporal t issue. The reduction in prostanoid production during hypoxia can be at tributed 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 prov ide mechanistic insight into the alteration in corporal blood homeosta sis during ischemic-hypoxic priapism.