Protective effects of BAY 41-2272 (sGC stimulator) on hypertension, heart, and cardiomyocyte hypertrophy induced by chronic L-NAME treatment in rats.
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.
Zanfolin
Marcos
M
CEMIB-Multidisciplinar Center for Biological Investigation, Faculty of Medical Sciences, Brazil.
Faro
Renato
R
Araujo
Eugênio G
EG
Guaraldo
Ana Maria Aparecida
AM
Antunes
Edson
E
De Nucci
Gilberto
G
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D006332:Cardiomegaly / Q000517:prevention & control*; D005355:Fibrosis; D006162:Guanylate Cyclase / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000517:prevention & control*; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000473:pathology; D019331:NG-Nitroarginine Methyl Ester / Q000633:toxicity*; D009569:Nitric Oxide / Q000096:biosynthesis; D011720:Pyrazoles / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
C423582:3-(4-Amino-5-cyclopropylpyrimidine-2-yl)-1-(2-fluorobenzyl)-1H-pyrazolo(3,4-b)pyridine; D011720:Pyrazoles; D011725:Pyridines; D009569:Nitric Oxide; D006162:Guanylate Cyclase; D019331:NG-Nitroarginine Methyl Ester