RESUMO
Current knowledge of atherogenesis is largely based on animal models of hypercholesterolemia, which rarely show changes similar to the lesions described in humans. We studied the influence of two low cholesterol-enriched diets on the development of anatomopathologic lesions and on the reactivity of the isolated aorta in rabbits. Compared with controls (rabbits fed a normal diet), a 0.1% cholesterol-enriched diet over a 6- or 9-month period produced increases of the 5-hydroxytryptamine (5-HT)-induced contractile responses, as well as a decreases in acetylcholine (ACh)-induced relaxing response (endothelium-dependent, through the production of NO). Noradrenaline (NA)-induced contractions and relaxations elicited by sodium nitroprusside (SNP; endothelium independent) were not significantly modified. Because at 6 months, significant anatomopathologic intimal early lesions were not found, functional endothelial changes can explain such findings. There was a defect in NO synthesis, release, or diffusion; 5 HT, but not NA, may be responsible for inducing NO production. In 0.2% cholesterol-fed rabbits at 4 and 12 weeks, increases of 5-HT- and NA-induced contractile responses were found. In both cases, there was a decrease of ACh-induced relaxing effect, whereas responses to SNP remained unchanged. Intimal early and advanced lesions were present at both the 4- and 12-week periods. These data suggest abnormalities of the NO system. The effects obtained with NA may be explained by a possible decrease of catechol-O-methyltransferase (COMT) or monoamine oxidase (MAO) activities or both or by decreased amine uptake. The extent to which NA may induce NO production is small, because changes in NA-induced contractions are verified only in the presence of significant alterations in the endothelium. The use of a 0.2% cholesterol diet for a short time may induce atherosclerotic lesions, whereas the 0.1% cholesterol diet for a 9-month period, besides being closer to the human diet, allows the detection of functional abnormalities before the evidence of structural lesions.
Assuntos
Arteriosclerose/etiologia , Colesterol na Dieta/efeitos adversos , Vasoconstrição/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos , Animais , Aorta/efeitos dos fármacos , Aorta/fisiologia , Arteriosclerose/patologia , Colesterol/sangue , Colesterol na Dieta/administração & dosagem , Relação Dose-Resposta a Droga , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiologia , Lipídeos/sangue , Masculino , Norepinefrina/farmacologia , Coelhos , Serotonina/farmacologia , Vasoconstritores/farmacologiaRESUMO
Using a model of experimental atherogenesis in New Zealand rabbits we found a lower noradrenaline level in the aorta than in the femoral artery. The activity of monoamine oxidase was decreased in the femoral artery and increased in the aorta of the cholesterol-fed animals when compared with controls.
Assuntos
Hipercolesterolemia/enzimologia , Monoaminoxidase/metabolismo , Animais , Aorta/enzimologia , Artéria Femoral/enzimologia , Masculino , Norepinefrina/análise , CoelhosAssuntos
Adenocarcinoma/patologia , Ensaios de Seleção de Medicamentos Antitumorais , Neoplasias Intestinais/patologia , Transplante de Neoplasias/patologia , Transplante Heterotópico/patologia , Adenocarcinoma/tratamento farmacológico , Animais , Biomarcadores Tumorais/análise , Feminino , Sobrevivência de Enxerto/fisiologia , Humanos , Técnicas Imunoenzimáticas , Mucosa Intestinal/patologia , Neoplasias Intestinais/tratamento farmacológico , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Ensaio de Cápsula Sub-RenalRESUMO
New Zealand White rabbits fed a low-level cholesterol-enriched diet (0.1%) were used to study and characterize a possible model of experimental atherogenesis. For the determination of the degree of atherosclerosis, more consistent and reproducible morphometric methods were used. Simultaneously the influence of plasma cholesterol levels on vascular noradrenaline content was studied. The effect of a new lipid-regulating drug (0.1% L 44-0, the N-oxide of a nicotinic acid derivative) on analyzed parameters was studied as well. This study suggests that the low-level cholesterol-enriched diet is atherogenic, with macroscopically detectable lesions of atherosclerosis becoming apparent by week 12 of the study. The same diet increases the vascular noradrenaline content in the renal artery and in the femoral artery and vein; however, it does not influence that content in the carotid and mesenteric arteries. L 44-0 counteracts most of the observed effects.