methylthiouracil and Arteriosclerosis

Following oral administration of methionine in high doses to normotensive (NR) and spontaneously hypertensive (SHR) rats, its degradation product, homocysteine (HC), which is markedly elevated in serum, exerts an angiotoxic action directed to the aorta. This is accompanied by considerable loss of endothelium and degeneration, partly with dissolution of the media cells with formation of characteristic processes of the degenerating mitochondria, and by elevated HC and cystathion (CT) values in the aortic wall. At the arterial vessels of other organs similar alterations did not occur. There are quantitative differences between NR and SHR. In SHR, serum shows higher HC and CT concentrations than in NR, and the methionine-related aortic alterations are considerably more pronounced and develop earlier, with the additional formation of connective tissue. Here, a certain dependence on the methionine dose is noted, in contrast to NR, for which the magnitude of the reaction appears to be more related to the length of time of methionine application. Additional administration of atherogenic substances (cholestane-3 beta, 5 alpha, 6 beta-triol, cholesterol, angiotensin II, cholic acid with methylthiouracil) in SHR causes an exacerbation of the methionine-related aortic alterations. Only cholestane-triol has the same effect on the aortic wall in NR and SHR, with more accentuation in SHR. Cholestane-triol has, in NR as well as in SHR, a high coincidence with methionine-induced morphological reactions including the formation of mitochondrial processes. Simultaneous application of these two substances did not cause a potentiation of the effect. High doses of cholesterol bring about aortic alterations in SHR but not in NR. Thus, in addition to the disorder of fat and carbohydrate metabolism, disturbed protein metabolism is of decisive importance as a risk factor for coronary and other vascular diseases.

Topics: Angiotensin II; Animals; Aorta; Arteriosclerosis; Cholestanols; Cholesterol; Cholic Acid; Cholic Acids; Endothelium, Vascular; Homocysteine; Hypertension; Hypolipidemic Agents; Male; Methionine; Methylthiouracil; Microscopy, Electron; Mitochondria; Rats; Rats, Inbred SHR; Rats, Wistar; Tunica Intima; Vasoconstrictor Agents

Due to present unavailability of Alkiron the authors tried to substitute it by Carbimazole in atherogenic diet aimed at inducing advanced atherosclerosis in rats. Carbimazole proved to be entirely ineffective in this respect and thus the thiouracil derivatives cannot be substituted by it.

Topics: Animals; Aorta; Arteriosclerosis; Carbimazole; Diet, Atherogenic; Female; Lipids; Methylthiouracil; Rats

Chronic investigations (up to 3 years) conducted in dogs have evidenced that periodic disturbances of vascular permeability produced by using dicoumarin with a long-term blocking of the thyroid function greatly aggravate pathological manifestations induced by the action of 6-methylthiouracil. They result in the development in the animals of endogenous hypercholesterinemia, elevated content in the blood of beta-lipoproteins and in a periodic rise of the arterial pressure. These changes were particularly spectacular at the final stage of the experiment in animals with marked manifestations of atherosclerosis and were accompanied by reduced stand-by potentialities of the adrenal gland, disruption of metabolic processes in the myocardium along with the slowed down resorption of NaI131 from the heart muscle. The sensitivity of the heart to adrenalin was down too.

Topics: 17-Hydroxycorticosteroids; Adrenal Cortex; Animals; Arteriosclerosis; Capillary Permeability; Dicumarol; Disease Models, Animal; Dogs; Lipids; Methylthiouracil

Topics: Animals; Aorta; Arteries; Arteriosclerosis; Capillary Permeability; Cholesterol; Coronary Vessels; Dicumarol; Dogs; Lipid Metabolism; Lipoproteins; Methods; Methylthiouracil

Topics: Amphetamine; Animals; Arteriosclerosis; Cholesterol; Disease Models, Animal; Humans; Mathematics; Methylthiouracil; Models, Theoretical; Oils; Rabbits

Topics: Animals; Arteries; Arteriosclerosis; Cholesterol; Dogs; Histocytochemistry; Methylthiouracil

Topics: Animals; Aorta; Arteriosclerosis; Cholesterol; Dogs; Galactose; Glucosamine; Mannose; Methylthiouracil; Phospholipids

Topics: Animals; Arteriosclerosis; Dicumarol; Diet, Atherogenic; Dietary Fats; Dogs; Electrocardiography; Hypercholesterolemia; Lipids; Methylthiouracil

Topics: Animals; Arteriosclerosis; Cardiovascular System; Cholesterol; Dogs; Hypercholesterolemia; Hypertension; Methylthiouracil

Topics: Animals; Arteriosclerosis; Atherosclerosis; Bile Acids and Salts; Cholesterol; Dietary Fats; Guinea Pigs; Lipid Metabolism; Methylthiouracil; Research; Salts

Topics: Arteriosclerosis; Atherosclerosis; Dietary Fats; Hypercholesterolemia; Methylthiouracil; Rats; Research; Toxicology

Topics: Arteriosclerosis; Blood Coagulation Factors; Cholesterol; Diet; Diet, Atherogenic; Ergocalciferols; Globulins; Lipids; Methylthiouracil; Thrombosis

Topics: Animals; Arteriosclerosis; Atherosclerosis; Methylthiouracil; Rats