Protective effects of BAY 41-2272 (sGC stimulator) on hypertension, heart, and cardiomyocyte hypertrophy induced by chronic L-NAME treatment in rats.

Abstract

This study evaluated the effects of BAY 41-2272 (BAY), a specific activator of sGC NO-independent action on changes of mean arterial blood pressure, heart and left ventricle weight indexes, cardiomyocyte hypertrophy (Vv) and fibrosis area induced by chronic N-nitro-L-arginine methyl ester (L-NAME) treatment in rats. The animals were divided into (a) control group, (b) L-NAME group, (c) L-NAME+BAY group, and (d) BAY group. Eight weeks of L-NAME treatment caused a significant increase in mean arterial blood pressure when compared with untreated rats (173 +/- 11.1 and 109 +/- 5.0 mm Hg, respectively; P < 0.01). L-NAME + BAY cotreatment abolished the L-NAME-induced hypertension (112 +/- 5.1 mm Hg; P < 0.01). Significant increases in heart and left ventricle weight indexes and in Vv were observed in the L-NAME-treated animals compared with control group, and concomitant treatment with BAY significantly attenuated this hypertrophic effect. Treatment with L-NAME presented several areas of repairing fibrosis in left ventricles, and this effect was also abolished by BAY cotreatment. Our results demonstrate that BAY 41-2272 inhibits hypertension and prevents heart abnormalities (cardiac hypertrophy and increased fibrosis areas) induced by NO synthase inhibition.

• Authors: Marcos Zanfolin, Renato Faro, Eugênio G Araujo, Ana Maria Aparecida Guaraldo, Edson Antunes, Gilberto De Nucci
• Journal: Journal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 47 Issue 3 Pg. 391-5 (Mar 2006) ISSN: 0160-2446 [Print] United States
• PMID: 16633081 (Publication Type: Journal Article)

Chemical References

• 3-(4-Amino-5-cyclopropylpyrimidine-2-yl)-1-(2-fluorobenzyl)-1H-pyrazolo(3,4-b)pyridine
• Pyrazoles
• Pyridines
• Nitric Oxide
• Guanylate Cyclase
• NG-Nitroarginine Methyl Ester

Topics

• Animals
• Blood Pressure (drug effects)
• Body Weight (drug effects)
• Cardiomegaly (prevention & control)
• Fibrosis
• Guanylate Cyclase (physiology)
• Heart Rate (drug effects)
• Hypertension (prevention & control)
• Male
• Myocytes, Cardiac (drug effects, pathology)
• NG-Nitroarginine Methyl Ester (toxicity)
• Nitric Oxide (biosynthesis)
• Pyrazoles (pharmacology)
• Pyridines (pharmacology)
• Rats
• Rats, Wistar