RESUMO
Serum low-density lipoproteins (LDL) and high-density lipoproteins (HDL) were prepared by gradient ultracentrifugation and dialysis from 12 healthy subjects and 15 patients with coronary heart disease and hyperlipoproteinemia. In both lipoprotein fractions cholesterol and lipid peroxides were determined. The effect of these lipoproteins on spontaneous prostacyclin biosynthesis in rat aortic slices was studied. Serum lipoproteins were susceptible to peroxidation during the preparation procedure. LDL were more prone to peroxidation than HDL. Little lipid peroxides were formed in lipoproteins when calcium ions had been removed by EDTA, and when butylated hydroxytoluene (BHT) was present at all stages of their preparation. LDL when prepared without these precautions either from healthy subjects or from patients with coronary heart disease markedly suppressed prostacyclin generation by rat aortic slices. This inhibition was unrelated to LDL-cholesterol, but was due to LDL-lipid peroxides. Peroxide-low LDL prepared from most of the healthy subjects and patients with coronary heart disease and concomitant hyperlipoproteinemia, did not inhibit prostacyclin biosynthesis. However, in one quarter of the patients, LDL was inhibitory. Consequently, in some patients with coronary heart disease, there operate unknown mechanisms which are responsible for the inhibitory activity of LDL on prostacyclin generation.
Assuntos
Doença das Coronárias/sangue , Epoprostenol/biossíntese , Peróxidos Lipídicos/sangue , Lipoproteínas/sangue , Prostaglandinas/biossíntese , Adulto , Idoso , Animais , Aorta/efeitos dos fármacos , Aorta/metabolismo , Feminino , Humanos , Peróxidos Lipídicos/farmacologia , Lipoproteínas HDL/sangue , Lipoproteínas HDL/farmacologia , Lipoproteínas LDL/sangue , Lipoproteínas LDL/farmacologia , Masculino , Pessoa de Meia-Idade , RatosRESUMO
Isolated perfused cat lungs secreted spontaneously a PGI2-like substance that relaxed a strip of bovine coronary artery. The presence of PGI2 was confirmed by the identification of 6-oxo-PGF1 alpha by GC-MS. Both bioassay and mass fragmentography showed that PGI2 was released at a rate of 4 - 12 ng/ml. Generation of PGI2 by the perfused cat lungs was stimulated by angiotensin II (3 - 10 ng/ml). The above results along with our in vivo experiments point to the lung as an important source of endogenous PGI2 in the body.
Assuntos
Angiotensina II/farmacologia , Epoprostenol/biossíntese , Pulmão/metabolismo , Prostaglandinas/biossíntese , Animais , Aorta/efeitos dos fármacos , Bioensaio , Gatos , Bovinos , Vasos Coronários/efeitos dos fármacos , Epoprostenol/farmacologia , Cromatografia Gasosa-Espectrometria de Massas , Pulmão/efeitos dos fármacos , Perfusão , CoelhosAssuntos
Aorta Torácica/metabolismo , Arteriosclerose/sangue , Plaquetas/metabolismo , Epoprostenol/biossíntese , Artérias Mesentéricas/metabolismo , Miocárdio/metabolismo , Prostaglandinas/biossíntese , Tromboxano A2/biossíntese , Tromboxanos/biossíntese , Animais , Ácidos Araquidônicos/administração & dosagem , Dieta Aterogênica , Masculino , Agregação Plaquetária/efeitos dos fármacos , CoelhosRESUMO
Experimental atherosclerosis in rabbits was associated with a suppression of prostacyclin generation from exogenous arachidonic acid by the coronary vascular bed. The spontaneous formation of prostacyclin by incubated rings of mesenteric artery was also diminished. These results suggest that in atherosclerosis an impaired activity of the endothelial prostacyclin synthexizing system contributes to the intra-arterial formation of thrombi.
