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Sildenafil reduces cardiovascular remodeling associated with hypertensive cardiomyopathy in NOS inhibitor-treated rats.
Eur J Pharmacol. 2006 Aug 07; 542(1-3):141-7.EJ

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.

Authors+Show Affiliations

Department of Pharmacology, Faculty of Medical Sciences, Institute of Biology, State University of Campinas, Campinas, SP, Brazil.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16806160

Citation

Ferreira-Melo, Silvia Elaine, et al. "Sildenafil Reduces Cardiovascular Remodeling Associated With Hypertensive Cardiomyopathy in NOS Inhibitor-treated Rats." European Journal of Pharmacology, vol. 542, no. 1-3, 2006, pp. 141-7.
Ferreira-Melo SE, Yugar-Toledo JC, Coelho OR, et al. Sildenafil reduces cardiovascular remodeling associated with hypertensive cardiomyopathy in NOS inhibitor-treated rats. Eur J Pharmacol. 2006;542(1-3):141-7.
Ferreira-Melo, S. E., Yugar-Toledo, J. C., Coelho, O. R., De Luca, I. M., Tanus-Santos, J. E., Hyslop, S., Irigoyen, M. C., & Moreno, H. (2006). Sildenafil reduces cardiovascular remodeling associated with hypertensive cardiomyopathy in NOS inhibitor-treated rats. European Journal of Pharmacology, 542(1-3), 141-7.
Ferreira-Melo SE, et al. Sildenafil Reduces Cardiovascular Remodeling Associated With Hypertensive Cardiomyopathy in NOS Inhibitor-treated Rats. Eur J Pharmacol. 2006 Aug 7;542(1-3):141-7. PubMed PMID: 16806160.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sildenafil reduces cardiovascular remodeling associated with hypertensive cardiomyopathy in NOS inhibitor-treated rats. AU - Ferreira-Melo,Silvia Elaine, AU - Yugar-Toledo,Juan Carlos, AU - Coelho,Otávio Rizzi, AU - De Luca,Iara M, AU - Tanus-Santos,José Eduardo, AU - Hyslop,Stephen, AU - Irigoyen,Maria Cláudia, AU - Moreno,Heitor,Jr Y1 - 2006/05/19/ PY - 2005/12/08/received PY - 2006/04/04/revised PY - 2006/04/10/accepted PY - 2006/6/30/pubmed PY - 2006/12/15/medline PY - 2006/6/30/entrez SP - 141 EP - 7 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 542 IS - 1-3 N2 - 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. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/16806160/Sildenafil_reduces_cardiovascular_remodeling_associated_with_hypertensive_cardiomyopathy_in_NOS_inhibitor_treated_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(06)00415-8 DB - PRIME DP - Unbound Medicine ER -