Numerical density of cardiomyocytes in chronic nitric oxide synthesis inhibition.
OBJECTIVE
The myocardial effect on the normalization of arterial blood pressure in animals with hypertension previously induced by nitric oxide synthesis (NOS) inhibition is still unknown. The purpose of this study was to estimate the numerical density of cardiomyocytes that is able to show cardiomyocyte loss as a consequence of NOS inhibition.


METHODS
Sixty rats were divided into the following groups: control for 25 days (C25), control for 40 days (C40) control for 80 days (C80) and three other groups in which the rats received the NOS inhibitor N(G)-nitro-L-arginine-methyl-ester hydrochloride L-NAME; 50 mg/kg/day for 25 days (L25), 40 days (L40) and 40 days, respectively, the latter group having another 40 days of only water and food ad libitum (without L-NAME; L80 group). The detection of apoptotic cells was performed using a monoclonal antibody.


RESULTS
In the L25, L40 and L80 groups, blood pressure was 74.5, 90.2 and 56.3% higher than the respective age-matched control rats, the myocardium had hypertrophy of the cardiomyocytes and scattered areas of fibrosis, and apoptosis occurred in isolated cells. Compared to the controls, the heart mass/body mass ratio was significantly greater in the L-NAME groups L25, L40 and L80, i.e. 31, 26 and 21%, respectively, the numerical density of cardiomyocytes in L-NAME rats was 32.7, 48.8 and 41.7% lower and the mean volume of cardiomyocytes was 33, 53 and 48% greater.


CONCLUSIONS
The cardiomyocyte loss in NOS inhibition seems to be mainly due to necrosis, although apoptosis is also present.
Mandarim-De-Lacerda
C A
CA
Laboratory of Morphometry and Cardiovascular Morphology, Biomedical Center, Institute of Biology, State University of Rio de Janeiro, Rio de Janeiro, Brazil. mandarim@uerj.br
Meirelles Pereira
L M
LM
D000818:Animals; D017209:Apoptosis; D002452:Cell Count / Q000187:drug effects; D004277:DNA, Single-Stranded / Q000032:analysis; D004791:Enzyme Inhibitors / Q000633:toxicity; D006321:Heart / Q000187:drug effects; D007124:Immunoenzyme Techniques; D008297:Male; D009206:Myocardium / Q000201:enzymology* / Q000473:pathology; D019331:NG-Nitroarginine Methyl Ester / Q000633:toxicity; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052250:Nitric Oxide Synthase Type III; D051381:Rats; D017208:Rats, Wistar
D004277:DNA, Single-Stranded; D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D019331:NG-Nitroarginine Methyl Ester