Allopurinol attenuates L-NAME induced cardiomyopathy comparable to blockade of angiotensin receptor.
It is widely recognized that L-NAME exposed rats develop myocardial fibrosis and hypertrophy. The aim of this study was to evaluate the contribution of xanthine oxidase (XO) to these phenomena using allopurinol, isolated or associated with olmesartan. Thirty adult male Wistar rats were divided into 5 groups (n=6) and studied for 5 weeks: L group (L-NAME, 40mg/kg/day); L+A group (L-NAME and allopurinol, 40 mg/kg/day); L+O group (L-NAME and olmesartan, 15mg/kg/day); L+A+O group (L-NAME, allopurinol, and olmesartan); and control group. L-NAME caused arterial hypertension and cardiomyocyte hypertrophy. Hypertension was prevented by olmesartan, but not by allopurinol. There was an increase of left ventricular mass index in the L-NAME group that was prevented by allopurinol, olmesartan and by the combination of both. The increase in mean cardiomyocyte transversal area caused by L-NAME was prevented by the allopurinol and olmesartan combination, or by olmesartan used as monotherapy, but not by allopurinol alone. There was a reduction in the myocardial vascularization index caused by L-NAME which was abolished by allopurinol or by olmesartan, but not by the association. L-NAME caused a reduction in the total number of cardiomyocyte nuclei. This was prevented by olmesartan alone or associated with allopurinol, but not by allopurinol alone. We conclude that XO has an important contribution to adverse cardiac remodeling in L-NAME exposed animals. Moreover, allopurinol acts without interfering with L-NAME induced hypertension. The protective action of this drug is comparable to the results obtained with olmesartan. Antioxidative mechanisms are proposed to account for the pressure independent effects of allopurinol.
Kasal
D A B
DA
Laboratory of Morphometry and Cardiovascular Morphology, Biomedical Center, Institute of Biology, Rio de Janeiro, Brazil.
Neves
M F
MF
Oigman
W
W
Mandarim-de-Lacerda
C A
CA
D000493:Allopurinol / Q000494:pharmacology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D009202:Cardiomyopathies / Q000201:enzymology / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006973:Hypertension / Q000139:chemically induced / Q000201:enzymology / Q000503:physiopathology / Q000517:prevention & control*; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D009206:Myocardium / Q000201:enzymology* / Q000473:pathology; D019331:NG-Nitroarginine Methyl Ester; D000068557:Olmesartan Medoxomil; D051381:Rats; D017208:Rats, Wistar; D013777:Tetrazoles / Q000494:pharmacology*; D013997:Time Factors; D014527:Uric Acid / Q000097:blood; D020257:Ventricular Remodeling / Q000187:drug effects; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors* / Q000378:metabolism
D047228:Angiotensin II Type 1 Receptor Blockers; D004791:Enzyme Inhibitors; D007093:Imidazoles; D013777:Tetrazoles; D014527:Uric Acid; D000493:Allopurinol; D000068557:Olmesartan Medoxomil; D014969:Xanthine Oxidase; D019331:NG-Nitroarginine Methyl Ester