Full text
| |
| Author(s): |
Silvia Elaine de Sousa Ferreira Carvalho de Melo
Total Authors: 1
|
| Document type: | Doctoral Thesis |
| Press: | Campinas, SP. |
| Institution: | Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas |
| Defense date: | 2005-04-25 |
| Examining board members: |
Heitor Moreno Junior;
Marta Helena Krieger;
Wilson Nadruz Junior;
Jose Eduardo Tanus Santos;
Francisco Rafael Laurindo
|
| Advisor: | Heitor Moreno Junior |
| 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 Nw¿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 restored 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 reversed 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 (AU) | |