Sildenafil preserves diastolic relaxation after reduction by L-NAME and increases phosphodiesterase-5 in the intercalated discs of cardiac myocytes and arterioles
Clinics
;
66(7): 1253-1258, 2011. ilus, tab
Article
in English
| LILACS
| ID: lil-596917
ABSTRACT
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.
Full text:
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Index:
LILACS (Americas)
Main subject:
Piperazines
/
Sulfones
/
NG-Nitroarginine Methyl Ester
/
Enzyme Inhibitors
/
Heart
/
Hypertension
Limits:
Animals
Language:
English
Journal:
Clinics
Journal subject:
Medicine
Year:
2011
Type:
Article
Affiliation country:
Brazil
Institution/Affiliation country:
USP/BR
/
Unicamp/BR
/
Universidade de São Paulo/BR
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