RESUMEN
Changes in the structure and functional properties of the vascular wall after 8 months of alimentary hypercholesterolemia (HCE) were studied. The experiments were conducted on the circular bands of the arch of the aorta in rabbits. Sharp inhibition of the reactivity of the vascular bands was established, which was associated first of all with thickening of the intima due to the development of fibro-atheromatous changes in it. At the same time, the smooth-muscle cells of the vascular wall maintained marked reactivity to various direct and receptor-mediated test effects. The functional significance of the endothelium in regulation of the vascular tonus, manifested by weakened endothelium-dependent relaxation, was sharply inhibited in the late stages of HCE. It is shown that reduction of the sensitivity of the smooth-muscle cells to the endothelium-dependent relaxation factor is the principal factor of weakening of the endothelium-dependent dilatational effects. After 8 months of HCE the aortic wall is capable of liberating a substance which is similar to the endothelium-dependent relaxation factor in its action, even when the thickened intima is completely removed.
Asunto(s)
Vasos Sanguíneos/fisiopatología , Hipercolesterolemia/fisiopatología , Animales , Conejos , Factores de TiempoRESUMEN
The authors studied the effect of various calcium antagonists--verapamil (VP) and Mg2+ (MgCl2) on the character of affection of the vascular wall ulcer conditions of prolonged hypercholesterolemia (HCE). The blood cholesterol (CS) content increased by the end of the 8th month of HCE to eight-fold the value in intact animals. The specific atherosclerotic changes in this case occupied approximately 80% of the area of the thoracic aorta whose functional properties changed essentially. The values of constricting responses of bands to noradrenaline (NA) was 45% of that in intact rabbits, the dilatating responses to acetyl choline (AC) and nitroglycerin (NG) were 20% and 35% of those in intact animals, respectively. Combination of HCE with daily VP injection (1 mg) led to a decrease in the area of affection of the aorta by 20%, which hardly affected the severity of HCE. A slightly more pronounced than in animals only with HCE (controls) was the response of bands to NA, AC, and NG (by 5, 30, and 15%, respectively). The protective effect of MgCl2 (200 mg/kg) was more significant--the affected area of the thoracic aorta reduced by 50% as compared to the controls, the constricting response to NA was maintained at a level exceeding the control level by 25%, the dilatating responses to NG and AC exceeded the control values 2 and 1.5 times, respectively, on the average. The severity of HCE diminished by 50%. The results of the study indicate that the organic and, in particular, the inorganic blocking agents of the calcium canals possess a marked angioprotective action and may be applied for the prevention of vascular atherosclerosis.
Asunto(s)
Arteriosclerosis/prevención & control , Bloqueadores de los Canales de Calcio/uso terapéutico , Endotelio Vascular/efectos de los fármacos , Cloruro de Magnesio/uso terapéutico , Verapamilo/uso terapéutico , Animales , ConejosRESUMEN
The authors studied the changes in the functional properties of a rabbit heart in protracted alimentary hypercholesterolemia (HCE). It is shown that HCE has a little effect on the characteristics of myocardial contractility and adrenergic sensitivity. In protracted HCE the probability of the occurrence of a myocardial own rhythm in response to the effect of isoprenaline increased. HCE with simultaneous vasopressin administration failed to change the contractile properties of the myocardium but had a marked effect on the adrenoreceptor apparatus. The sensitivity of muscles to isoprenaline and phenylephrine increased significantly. The possibility of the appearance of a myocardial own rhythm increased. The results of the study are indicative of the essential role of vasospasm in the development of atherosclerotic myocardial injuries.
Asunto(s)
Arteriosclerosis/fisiopatología , Cardiotónicos/farmacología , Corazón/fisiopatología , Receptores Adrenérgicos/efectos de los fármacos , Animales , Corazón/efectos de los fármacos , Corazón/inervación , ConejosRESUMEN
The course of the rabbit aortic wall reactivity changes due to hypercholesterolemia involved, in the first place, the inhibition of the endothelium relaxing influence on the smooth muscle contractile activity and an increase in the muscle sensitivity to neurogenic and humoral tonic influences. Later, a sharp inhibition of the vessel's wall functional activity occurred due to a mechanical factor: the development of connective tissue which prevents active vascular reactions. Nevertheless, endothelial and smooth muscle cells functional activity was high enough. The main cause of the vascular reactivity disturbances involved structural changes in the vessel wall whilst the direct influence of high blood cholesterol was much less obvious.
Asunto(s)
Endotelio Vascular/fisiopatología , Hipercolesterolemia/fisiopatología , Músculo Liso Vascular/fisiopatología , Acetilcolina/farmacología , Animales , Aorta/efectos de los fármacos , Aorta/fisiopatología , Calcimicina/farmacología , Enfermedad Crónica , Dieta Aterogénica , Endotelio Vascular/efectos de los fármacos , Contracción Muscular/efectos de los fármacos , Contracción Muscular/fisiología , Músculo Liso Vascular/efectos de los fármacos , Nitroglicerina/farmacología , Norepinefrina/farmacología , Fenilefrina/farmacología , ConejosRESUMEN
The investigations were performed on the ring strips of rabbit aorta. The electrical activity of the vessels smooth muscle cells was registered by the "sucrose gap" method; the contractile activity of the strips was determined simultaneously. Experimental atherosclerosis was induced by keeping rabbits on a special diet enriched by cholesterol for 2 and 4 months. Strips were prepared with intact or mechanically removed endothelium. Hypercholesterolemia was shown to inhibit the reactivity of the vessel's wall to the weakening action of acetylcholine due to endothelial stimulation. The cause of these changes was the inhibition of the endothelial functional activity and inactivation of mechanisms by which endothelium influences smooth muscle cells.
Asunto(s)
Endotelio Vascular/fisiología , Hipercolesterolemia/fisiopatología , Contracción Muscular , Acetilcolina/farmacología , Animales , Arteriosclerosis/fisiopatología , Endotelio Vascular/efectos de los fármacos , Técnicas In Vitro , Contracción Muscular/efectos de los fármacos , Músculo Liso Vascular/efectos de los fármacos , Músculo Liso Vascular/fisiopatología , Nitroglicerina/farmacología , ConejosRESUMEN
Acetylcholine and nitroglycerin were shown to induce relaxation in muscles of the ring vascular segments of canine coronary arteries and rabbit aortic archs, the magnitude of the reaction depending on the level of initial tonic tension. Methylene blue abolished the relaxation. Mechanical removal of endothelium abolished the reaction to acetylcholine but not to nitroglycerin. Verapamil decreased the relaxation by 70%. The endothelium-dependent relaxation seems to be connected mainly with a decrease in the calcium entering vascular smooth muscle cells through voltage-dependent channels.