Phosphodiesterase type 5 expression in human and rat lower urinary tract tissues and the effect of tadalafil on prostate gland oxygenation in spontaneously hypertensive rats.
Level 5 - mechanism / opinion, no new human data
Preclinical bench and animal study (in vitro human tissue and rodent model)
PubMed 21812935 · doi:10.1111/j.1743-6109.2011.02416.x
What was done
The authors examined phosphodiesterase type 5 (PDE5) expression and activity in human vesicular-deferential arteries using quantitative RT-PCR, immunohistochemistry, and cyclic guanosine monophosphate (cGMP) breakdown assays with tadalafil and sodium nitroprusside. In vivo, spontaneously hypertensive rats (SHR), which exhibit genitourinary ischemia, were treated with tadalafil (2 mg/kg/day) for 1, 7, or 28 days and compared to untreated SHR and normotensive Wistar-Kyoto (WKY) controls. Prostatic oxygenation and hypoxia markers (Hypoxyprobe-1, HIF-1α, ETB, and the HIF-1α target gene BNIP3) were measured.
What was found
Human vesicular-deferential arteries demonstrated high PDE5 expression localized to endothelial and smooth muscle layers, with tadalafil inhibiting cGMP breakdown at an IC50 in the low nanomolar range and enhancing sodium nitroprusside-induced relaxation. In untreated SHR, prostate tissue showed marked hypoxia with elevated Hypoxyprobe immunopositivity, HIF-1α, and ETB staining. Tadalafil treatment restored prostate oxygenation to WKY control levels at 1, 7, and 28 days, and partially restored the elevated mRNA expression of BNIP3 toward control levels.
Why it matters
This study provides a mechanistic basis for how PDE5 inhibitors may alleviate lower urinary tract symptoms, suggesting they improve pelvic blood supply and reverse prostatic hypoxia.
Limits
The study is restricted to in vitro human vascular preparations and an animal model of hypertension-induced ischemia. Exact sample sizes and quantitative numerical values (beyond general IC50 ranges) were not reported in the abstract. Clinical efficacy and direct perfusion changes in human prostate tissue were not evaluated.
Cited by
- partial Low-dose tadalafil (2.5 to 5 mg per day) is effective for improving perfusion of the prostate.