Influence of the chronic nitric oxide synthesis inhibition on cardiomyocytes number.
This work analyzes the relationship between the number of viable cells and alteration of the cardiomyocytes growth response capacity of the hypertensive rat myocardium. Hypertension was induced in Wistar rats by means of nitric oxide synthesis blockade using NG-nitro-L-arginine methyl ester (L-NAME). L-NAME (12 mg/kg per day) was given to animals in drinking water ad lib for 15 weeks. Proliferating cell nuclear antigen (PCNA) protein expression and the disector method were used to evaluate the proliferation capacity of the cardiomyocytes and its numerical density alteration (Nv[m]), respectively. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) and monoclonal antibody to single-stranded DNA were two methods that detected the process of the apoptotic cell death. The association of the p53 expression with the apoptosis was investigated using anti-p53 antibody. The heart weight, body weight, and heart weight/body weight ratio of the control rats increased 114%, 77%, and 22%, respectively, and the Nv[m] decreased 60% (P<0.0001) relative to the L-NAME rats. The cardiomyocytes did not present PCNA labeling, indicating the absence of cellular proliferation. The decline of the Nv[m] was also associated with apoptotic cell death in the myocardium of the hypertensive rats. A p53-dependent pathway seems to mediate the programmed cell death in this model of hypertension.
Pessanha
M G
MG
Laboratório de Morfometria, UERJ, Instituto de Biologia, Centro Biomédico, Rio de Janeiro, Brasil. mgpessanha@hotmail.com
Mandarim-de-Lacerda
C A
CA
D000818:Animals; D000911:Antibodies, Monoclonal; D017209:Apoptosis; D002452:Cell Count; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006973:Hypertension / Q000139:chemically induced* / Q000201:enzymology / Q000473:pathology; D020287:In Situ Nick-End Labeling; D008297:Male; D009206:Myocardium / Q000737:chemistry / Q000201:enzymology / Q000473:pathology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
D000911:Antibodies, Monoclonal; D004791:Enzyme Inhibitors; D018809:Proliferating Cell Nuclear Antigen; D016159:Tumor Suppressor Protein p53; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester