Sildenafil reduces cardiovascular remodeling associated with hypertensive cardiomyopathy in NOS inhibitor-treated rats.

Abstract:

:Many of the physiological responses to nitric oxide (NO) are mediated by cyclic 5'-guanosine monophosphate (cGMP), the intracellular levels of which are regulated by phosphodiesterase type 5 (PDE5). In situations of reduced NO formation, the inhibition of PDE5 by selective inhibitors such as sildenafil could be beneficial in restoring physiological functions by enhancing the intracellular levels of cGMP. In this study, we evaluated the effects of sildenafil on the hemodynamic and histological alterations induced by the chronic treatment of rats with N(omega)-nitro-L-arginine-methyl ester (L-NAME). After 8 weeks of concomitant treatment with sildenafil and L-NAME, arterial blood pressure was significantly lower (P<0.05) than in L-NAME-treated rats. The fall in blood pressure was associated with a slight reduction in the total peripheral vascular resistance (P<0.05). Sildenafil partially prevented the decrease in cardiac output seen in L-NAME-treated rats. Morphologically, sildenafil reduced the total area of the myocardial lesions and attenuated the cardiomyocyte and vascular smooth muscle remodeling seen with L-NAME. These results show that sildenafil prevented the deleterious hemodynamic and morphological alterations associated with L-NAME-induced hypertension. This beneficial effect was probably mediated by an increase in cardiac and vascular cGMP levels as reflected in circulating plasma cGMP levels.

journal_name

Eur J Pharmacol

authors

Ferreira-Melo SE,Yugar-Toledo JC,Coelho OR,De Luca IM,Tanus-Santos JE,Hyslop S,Irigoyen MC,Moreno H Jr

doi

10.1016/j.ejphar.2006.04.039

subject

Has Abstract

pub_date

2006-08-07 00:00:00

pages

141-7

issue

1-3

eissn

0014-2999

issn

1879-0712

pii

S0014-2999(06)00415-8

journal_volume

542

pub_type

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