Aorta products

Other surgical implants are essentially plastic repair products for worn out parts of the body. It is possible to conceive of major replacements of an entire organ such as a kidney or a heart by combining the plastic skills with tissue regeneration efforts that may extend life. This is used to time the heart action. Extensively used are plastic corrugated, fiber (silicone or TP polyester) braided aortas (24). 

A relationship between polyol pathway activity and reduction in endothelium-dependent relaxation in aorta from chronic STZ-diabetic rats has recently been reported (Cameron and Cotter, 1992). In agreement with several previous studies (Oyama et al., 1986 Kamata et al., 1989), endothelial-dependent relaxation was defective in the diabetic rats but the deficit was prevented by prior treatment with an AR inhibitor. The mechanism underlying the defect has been speculated to be due to decreased production of endothelium-derived relaxing factor (EDRF) or nitric oxide, NO (Hattori et al., 1991). It has been speculated that these vascular abnormalities may lead to diminished blood flow in susceptible tissues and contribute to the development of some diabetic complications. NO is synthesized from the amino-acid L-arginine by a calcium-dependent NO synthase, which requires NADPH as a cofactor. Competition for NADPH from the polyol pathway would take place during times of sustained hyperglycaemia and... 

Humans may be exposed to hydrogen sulfide both from its endogenous production or from exogenous sources. Most endogenous production apparently results from the metabolism of sulfhydryl-containing amino acids, e.g., cysteine, by bacteria present in both the intestinal tract and the mouth (Beauchamp et al. 1994 Tonzetich and Carpenter 1971) however, it is also produced in the brain and several smooth muscles, e.g., thoraic aorta, by enzymes found in these tissues (Abe and Kimura 1996 Hosoki et al. 1997). 

Cultured rat vascular smooth muscle cells (VSMCs), grown and prepared for respirometry as described in Doeller et al., 2005 [41], were injected into the respirometer chamber to a concentration of between 105 and 106 cells ml 1. Cell viability remained at >90% throughout experiments. Near 4pM 02, H2S production was stimulated by the addition of L-cysteine and PLP (Fig. 8.8). The initial H2S production rate was approximately 20% of the rat aorta homogenate rate. H2S production rate decreased after the initial rise in H2S concentration, perhaps the result of product feedback inhibition. The addition of the CGL inhibitor BCA showed an effect similar to aorta homogenate. 

FIGURE 8.8 H2S production in vascular tissues. IPS production by aorta homogenate (upper panel), cultured rat vascular smooth muscle cells (VSMCs middle panel), and intact rat aorta occurs after the addition of substrate L-cysteine (L-cys) and cofactor pyridoxal L-phosphate (PLP) for the enzyme CGL located in vascular tissue. H2S production is inhibited after the CGL. 3 cyano-L-alanine (BCA) is added. Ferric Lucina pectinata hemoglobin I (metHb) is added to confirm H2S production. The quantity of metHb-sulfide produced, determined spectrophotometrically, matched the levels of H2S detected by the PHSS (after [41]). 

The expression of 15-LOX in atherosclerotic lesions is one of the major causes of LDL oxidative modification during atherosclerosis. To obtain the experimental evidence of a principal role of 15-LOX in atherosclerosis under in vivo conditions, Kuhn et al. [67] studied the structure of oxidized LDL isolated from the aorta of rabbits fed with a cholesterol-rich diet. It was found that specific LOX products were present in early atherosclerotic lesions. On the later stages of atherosclerosis the content of these products diminished while the amount of products originating from nonenzymatic lipid peroxidation increased. It was concluded that arachidonate 15-LOX is of pathophysiological importance at the early stages of atherosclerosis. Folcik et al. [68] demonstrated that 15-LOX contributed to the oxidation of LDL in human atherosclerotic plaques because they observed an increase in the stereospecificity of oxidation in oxidized products. Arachidonate 15-LOX is apparently more active in young human lesions and therefore, may be of pathophysiological importance for earlier atherosclerosis. In advanced human plaques nonenzymatic lipid peroxidation products prevailed [69],... 

It should be mentioned that the inhibition of superoxide overproduction and lipid peroxidation by lipoic acid has been recently shown in animal models of diabetes mellitus. The administration of LA to streptozotocin-diabetic rats suppressed the formation of lipid peroxidation products [213], In another study the supplementation of glucose-fed rats with lipoic acid suppressed aorta superoxide overproduction as well as an increase in blood pressure and insulin resistance [214]. 

It has been found that the 3-hydroxy-3-methylglutaryl-CoA (HMG CoA) inhibitors statins (atorvastatin, pravastatin, and cerivastatin), widely prescribed cholesterol-lowering agents, are able to inhibit phorbol ester-stimulated superoxide formation in endothelial-intact segments of the rat aorta [64] and suppress angiotensin II-mediated free radical production [65]. Delbose et al. [66] found that statins inhibited NADPH oxidase-catalyzed PMA-induced superoxide production by monocytes. It was suggested that statins can prevent or limit the involvement of superoxide in the development of atherosclerosis. It is important that statin... 

As in the case of other cardiovascular diseases, the possibility of antioxidant treatment of diabetes mellitus has been studied in both animal models and diabetic patients. The treatment of streptozotocin-induced diabetic rats with a-lipoic acid reduced superoxide production by aorta and superoxide and peroxynitrite formation by arterioles providing circulation to the region of the sciatic nerve, suppressed lipid peroxidation in serum, and improved lens glutathione level [131]. In contrast, hydroxyethyl starch desferrioxamine had no effect on the markers of oxidative stress in diabetic rats. Lipoic acid also suppressed hyperglycemia and mitochondrial superoxide generation in hearts of glucose-treated rats [132],... 

Dimethyl-l,2,5-oxadiazolo[3,4-d]pyridazine 1,5,6-trioxide (41) is also an old product [7,11, 31] that has recently been found to react with GSH to give S-nitrosogluta-thione, NO and HNO [32]. It stimulates partially purified rat lung soluble guanylate cyclase, but not the heme-deficient enzyme. The activation is inhibited by ODQ. The product also displays significant vasodilator activity on rat thoracic aorta rings at nanomolar concentrations. Finally, [l,2,5]oxadiazolo[3,4-d]pyrimidine-5,7-dione 1-oxide derivatives (42, R,Ri=CH3,H) release NO, detected as nitrite, in the presence of thiols. A mechanism for this release has been proposed [33]. 

Spasmolytic activity. Ethanol (95%), ethanol/glycerin, and glycerin extracts of the leaf, administered to guinea pigs at a dose of 50 mg/kg, was active vs vasopressin-induced coronary spasms as determined from electrocardiogram ". Ethanol (30%) extract of the dried leaf, administered to rabbits at a concentration of 1 mg/mL, was active on aorta vs K -induced contractions ". Decoction of the dried leaf, administered to rats, was active on aorta, IC501.12 mg/mL. The effect of the lyophilized extract on phenylephrine-induced contraction and endothelium was present. Decoction of the dried leaf, administered to rats, was active on the aorta vs phenylephrine-induced contraction, IC501.16 mg/mL. Water extract of the dried leaf, administered to rats at a dose of 3 mg/mL, was active on trachea vs acetylcholine-induced contractions ". Superoxide production inhibition. Seed oil, administered to rats at a concentration... 

Benito, S., Lopez, D., Saiz, M.P., Buxaderas, S., Sanchez, J., Puig-Parellada, P., and Mitjavila, M.T., A flavonoid-rich diet increases nitric oxide production in rat aorta, Br. J. Pharmacol, 135, 910, 2002. 

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