OBJECTIVES: We investigated the influence of
sildenafil on cardiac contractility and diastolic
relaxation and examined the distribution of
phosphodiesterase-5 in the
hearts of hypertensive
rats that were treated with by
NG-nitro-L-arginine methyl ester (
L-NAME ).
METHODS: Male Wistar rats were treated with
L-NAME and/or
sildenafil for eight weeks. The Langendorff
method was used to examine the effects of
sildenafil on cardiac contractility and diastolic
relaxation . The presence and
location of
phosphodiesterase-5 and phosphodiesterase-3 were assessed by
immunohistochemistry , and cGMP
plasma levels were measured by
ELISA .
RESULTS: In isolated
hearts ,
sildenafil prevented the reduction of diastolic
relaxation (dP/dt) that was induced by
L-NAME . In addition,
phosphodiesterase-5 immunoreactivity was localized in the intercalated discs between the myocardial
cells . The
staining intensity was reduced by
L-NAME , and
sildenafil treatment abolished this reduction. Consistent with these results, the
plasma levels of cGMP were decreased in the
L-NAME -treated
rats but not in
rats that were treated with
L-NAME +
sildenafil .
CONCLUSION: The
sildenafil -induced attenuation of the deleterious
hemodynamic and cardiac morphological effects of
L-NAME in
cardiac myocytes is mediated (at least in part) by the inhibition of
phosphodiesterase-5 .