Previous studies concerning ischemic priapism revealed that hypoxia alters the erectile and contractile responses of penis. But the effects of accompanying acidosis on those responses have not been fully evaluated or understood yet. We performed this study to elucidate the role of acidosis on the trabecular smooth muscle contractility like in ischemic priapism.Under the general anesthesia, 55 mature male cats were conditioned to systemic metabolic acidosis by hypoventilation by animal ventilator. The changes of intracavernous pressure (ICP) to erectogenic agents (acetylcholine, L-arginine, prostaglandin E 1 : PGE 1 ), erectolytic agents (epinephrine, thromboxane A 2 ; TXA 2 ), K channel-related drugs (pinacidil, 4-aminopyridine, tetraethylammonium; TEA, glibenclamide) and calcium ionophore were monitored at Set 1 (PO 2 b 60 mmHg, pH b 7.25), Set 2 (PO 2`3 0 mmHg, 7.25 b pH b 7.0), Set 3 (PO 2`3 0 mmHg, pH`7.0), and Set 4 (PO 2 b 60 mmHg, pH`7.0) in vivo.At Set 1 and Set 2, epinephrine, TXA 2 , and ionomycin decreased the ICP by acetylcholine or PGE 1 (n 9, P`0.01). The decrease of ICP was in order of epinephrine, TXA 2 and ionomycin. Acidosis reduced the increase of ICP to acetylcholine or PGE 1 (n 8, P`0.01), TXA 2 or ionomycin did not affect ICP under severe acidosis but epinephrine decreased ICP even under severe acidosis (n 7, P`0.05). Pretreatment of potassium channel blockers did not suppress the increase of ICP by erectogenic agents under acidosis (n 6, P`0.05). Pinacidil did not affect ICP under acidosis (n 6, P`0.01).These results suggest that acidosis impairs the contractile response of cavernous smooth muscle to erectolytic agents. It may be the results of the interference by [H ] with the intra and extracellular mechanisms that regulate the homeostasis of [Ca 2 ]. Conclusively, besides hypoxia, acidosis is another limiting factor of trabecular smooth muscle contractility like in ischemic priapism.

These results suggest that pinacidil is effective in relaxing feline erectile tissue in vivo, probably via increased K+ permeability and subsequent hyperpolarization. Further comparative studies with erectogenic compounds on human erectile tissue and clinical testing are required to determine whether K+-channel openers can be used in the diagnosis and treatment of erectile dysfunction. However, pinacidil seems promising as an intracavernosal agent combined with PGE1 to produce synergistic effects.