Premium
Threshold gene transfer with hSlo enhances sildenafil‐induced erectile responses in 2 month streptozotocin(STZ)‐diabetic rats
Author(s) -
Zhao Weixin,
Machingal Masood,
Turner Chanda,
Davies Kelvin,
Andersson KarlErik,
Melman Arnold,
Christ George J.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a420-c
Subject(s) - sildenafil , streptozotocin , erectile dysfunction , potassium channel opener , erectile tissue , medicine , endocrinology , nitric oxide , priapism , intracavernous injection , potassium channel , chemistry , diabetes mellitus , surgery
Both K channels and the nitric oxide (NO)/cGMP pathway play a critical role in erectile physiology/dysfunction. The purpose of this study was to investigate the effect of K channel gene transfer with hSlo (pore‐forming subunit of the human maxi‐K channel) on cavernous nerve (CN) stimulated intracavernous pressure (ICP) responses in the absence and presence of the PDE‐5 inhibitor sildenafil (SIL). 40 F‐344 rats were made diabetic (DM) with streptozotocin (STZ). 2 months after confirmation of DM, 10 μg pVAX/ hSlo was injected into the corpus cavernosum of 20 rats. A week later, control CN stimulations were obtained at 4 mA (a consistent non‐erectile stimulus) and then repeated on the same animal after the IV injection of SIL with using ICP/BP. (1) DM‐0.1 mg/kg SIL (n=10), 0.42±0.01 before, and 0.57±0.01 a after; 2: DM‐1 mg/kg SIL (n=10), 0.42±0.01 before, and 0.59±0.02 a after; 3: DM+hSlo‐0.1 mg/kg SIL (n=10), 0.44±0.01 before, and 0.66±0.02 ab after; 4: DM+hSlo‐1 mg/kg SIL (n=10), 0.43±0.01 before, and 0.84±0.02 ab after;5: a: Sig. different from before SIL and b: Sig. different from DM. Increases were observed in ICP/BP after SIL in all groups, but in the presence of hSlo the responses to SIL were enhanced at both doses. The data suggests that combination therapy with low‐dose gene transfer and orally active agents may increase the efficacy and logically reduce side effects of the latter (Pfizer).