The phosphodiesterase 5 inhibitor tadalafil has renoprotective effects in a rat model of chronic kidney disease
Male
Rats, Inbred Dahl
Physiology
phosphodiesterase 5 inhibitors
Blood Pressure
Phosphodiesterase 5 Inhibitors
renoprotection
Rats
Tadalafil
3. Good health
Proteinuria
03 medical and health sciences
0302 clinical medicine
Creatinine
Plasminogen Activator Inhibitor 1
QP1-981
Animals
Renal Insufficiency, Chronic
tadalafil
chronic kidney disease
Original Research
DOI:
10.14814/phy2.14556
Publication Date:
2020-09-05T15:45:16Z
AUTHORS (8)
ABSTRACT
Phosphodiesterase 5 inhibitors are widely used to treat erectile dysfunction and lower urinary tract symptoms with benign prostatic hyperplasia. Recent studies have indicated the renoprotective effects of this class of compounds. Whether renoprotection depends on blood pressure reduction remains controversial. In this study, we investigated the renoprotective effects of the phosphodiesterase 5 inhibitor, tadalafil, in a rat model of high-salt induced kidney injury with hypertension. Dahl salt-sensitive rats were fed a normal diet, high-salt (8% sodium chloride) diet, or high-salt diet with oral administration of either low- or high-dose tadalafil (1 and 10 mg kg-1 day-1 , respectively). Serum creatinine, urinary protein, and blood pressure were measured at baseline and after 8 weeks, at which point the rats were examined for glomerular injury and fibrosis. PAI1 mRNA levels were also evaluated. After 8 weeks, blood pressure, serum creatinine, and urinary protein levels were significantly higher in the high-salt group than those in the normal-salt group. Serum creatinine and urinary protein were significantly lower in both tadalafil groups than those in the high-salt group, while only high-dose tadalafil affected blood pressure. In addition, glomerulosclerosis and α-smooth muscle actin expression significantly decreased in both tadalafil treatment groups. PAI1 mRNA increased significantly in the high-salt group but decreased in both tadalafil-treated groups. Our results indicated that both low- and high-dose tadalafil prevented fibrosis and glomerular injury in a chronic kidney disease rat model. Mechanistically, these effects may be associated with PAI1 expression and glomerular structure protection.
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