RESUMO
To determine the effects of aging on vasoactivity in a primate model (Macaca fascicularis), 13 young male monkeys (aged 7.1+/-0.4 years) and 9 old male monkeys (aged 19.8+/-0.6 years) were chronically instrumented for measurement of left ventricular and aortic pressures and cardiac output. Total cholesterol, triglyceride, and fasting blood sugar levels were not different between the 2 groups. There were no significant differences in baseline mean aortic pressure and total peripheral resistance (TPR) in the young monkeys versus the old monkeys. TPR fell less (P<0.05) with acetylcholine (1 microg/kg) in old monkeys (-25+/-1%) than in young monkeys (-34+/-2%), whereas decreases in TPR with sodium nitroprusside were similar in old and young monkeys. There was no evidence of atherosclerosis, but apoptosis of endothelial cells was enhanced (P<0.05) in the aortas and femoral arteries, but not in the media, of the old monkeys. There was a relationship (r=0.62, P=0.013) between the incidence of terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL)-positive endothelial cells and endothelial cell density in the femoral artery. The reduced endothelial cell density was also correlated (r=0.82, P<0.01) with depressed TPR responses to acetylcholine. Thus, vascular endothelial dysfunction was present in old monkeys without evidence of atherosclerosis, which may be due to endothelial apoptosis and reduced endothelial cell density.
Assuntos
Envelhecimento/fisiologia , Endotélio Vascular/fisiologia , Acetilcolina/farmacologia , Animais , Aorta Abdominal/citologia , Aorta Abdominal/efeitos dos fármacos , Aorta Abdominal/fisiologia , Aorta Torácica/citologia , Aorta Torácica/efeitos dos fármacos , Aorta Torácica/fisiologia , Apoptose , Pressão Sanguínea/efeitos dos fármacos , Contagem de Células , Endotélio Vascular/citologia , Endotélio Vascular/efeitos dos fármacos , Artéria Femoral/citologia , Artéria Femoral/efeitos dos fármacos , Artéria Femoral/fisiologia , Marcação In Situ das Extremidades Cortadas , Macaca fascicularis , Masculino , Nitroprussiato/farmacologia , Resistência Vascular/efeitos dos fármacos , Vasodilatadores/farmacologiaRESUMO
A nonhuman primate model of tuberculosis that closely resembles human disease is urgently needed. We have evaluated the Philippine cynomolgus monkey, Macaca fasicularis, as a model of TB. Cynomolgus monkeys challenged intratracheally with extremely high doses of Mycobacterium tuberculosis (10(5) or 10(4) CFU) developed an acute, rapidly progressive, highly fatal multilobar pneumonia. However, monkeys challenged with moderate or low doses of M. tuberculosis (
Assuntos
Modelos Animais de Doenças , Doenças dos Macacos/fisiopatologia , Mycobacterium tuberculosis , Tuberculose Pulmonar/veterinária , Doença Aguda , Animais , Doença Crônica , Humanos , MacacaRESUMO
Large-scale breeding of Macaca fascicularis in the country of origin is a way in which the demands of the research community can be met whilst the feral population of monkeys is safeguarded. The establishment of the SICONBREC project and the success of its breeding programme to date is clear evidence of the future trend in the supply of non-human primates for biomedical research.