Atorvastatin but not elocalcitol increases
نویسندگان
چکیده
27 Spontaneously hypertensive rats (SHR) are characterized by impaired erectile function and by 28 overactivity of the pro-contractile RhoA/Rho-kinase (RhoA/ROCK) pathway, as compared to their 29 normotensive counterpart, Wistar Kyoto rats. By measuring intracavernous pressure/mean arterial 30 pressure (ICP/MAP) ratio after electrostimulation of the cavernous nerve, we confirmed these findings 31 and showed that also responsiveness to sildenafil (25 mg/kg by oral gavage) is hampered in SHR. A 32 two-week treatment with atorvastatin (5 and 30 mg/kg) improved sildenafil-induced ICP/MAP increase 33 and normalized RhoA and ROCK2 over-expression (qRT-PCR) in SHR corpora cavernosa (CC). 34 Conversely, other genes, nNOS, eNOS and PDE5, were unaffected. In human foetal smooth muscle 35 cells derived from CC (hfPSMC), atorvastatin inhibited RhoA membrane translocation and ROCK 36 activity as well as RhoA-dependent biological functions, like cell migration and proliferation. 37 Atorvastatin effect on migration was dose-dependently rescued by geranylgeranyl pyrophosphate, 38 suggesting the involvement of RhoA geranylgeranylation. In hfPSMC, atorvastatin decreased the 39 expression of RhoA-dependent genes as ROCK2, desmin, α-smooth muscle actin, SM22α and 40 myocardin. In contrast to atorvastatin, elocalcitol, a vitamin D analogue, which also interferes with 41 RhoA activation in SHR bladder, was unable to restore penile responsiveness to sildenafil. In 42 conclusion, atorvastatin, but not elocalcitol, ameliorates sildenafil-induced penile erections in SHR rats, 43 likely by interfering with RhoA/ROCKs signaling within the penis. 44 45
منابع مشابه
Atorvastatin but not elocalcitol increases sildenafil responsiveness in spontaneously hypertensive rats by regulating the RhoA/ROCK pathway.
Spontaneously hypertensive rats (SHR) are characterized by impaired erectile function and overactivity of the procontractile RhoA/Rho-associated, coiled-coil-containing protein kinase (RhoA/ROCK) pathway, as compared with their normotensive counterpart, Wistar-Kyoto rats. By measuring the intracavernous pressure:mean arterial pressure (ICP:MAP) ratio after electrostimulation of the cavernous ne...
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