Gene transfer of the KATP channel restores age‐related erectile dysfunction in rats

Abstract

To determine if gene transfer of the ATP-sensitive potassium (K(ATP)) channel can reverse age-related erectile dysfunction in the rat, as the K(ATP) channel is an important subtype of potassium channels regulating smooth muscle tone. In an in vitro study, gene were transferred using cDNA of the K(ATP) channel in cultured human corporal smooth muscle (CSM) cells and human embryonic kidney (HEK) cells. After gene transfer, the activities of transferred channels were assessed by the patch-clamp technique. In an in vivo study, 15 old rats were used for groups of gene therapy and nine young adult rats were used as normal controls. The old rats were divided into three groups, i.e. controls and two gene-transfer groups (Kir6.1 + SUR2B and Kir6.2 + SUR2B). The intracavernosal pressure (ICP) response to cavernosal nerve stimulation was assessed after intracorporal injection with naked cDNA of the K(ATP) channel. The transgene expression of the K(ATP) channel was examined by reverse transcription-polymerase chain reaction (RT-PCR) in rats transfected with cDNA of Kir 6.1 and 6.2. The transferred gene of the K(ATP) channel was functionally active and appropriate for gene transfer. The mean (sem) ratio of ICP to systemic blood pressure in the gene-transfer groups, at 79.4 (1)% and 76.5 (2.6)% (both eight rats) was significantly higher than that in age-matched control rats, at 59.4 (3.3)% (eight), and similar to that in the young control rats, at 77.1 (2.7)% (nine). The RT-PCR showed expression of Kir6.1 and 6.2 genes in the transfected groups. In vivo gene transfer of the K(ATP) channel can physiologically restore erectile function in aged rats, and might be applicable to the development of new forms of therapy for treating human erectile dysfunction.