Vascular smooth muscle, vitamin

Lead is toxic to the kidney, cardiovascular system, developiag red blood cells, and the nervous system. The toxicity of lead to the kidney is manifested by chronic nephropathy and appears to result from long-term, relatively high dose exposure to lead. It appears that the toxicity of lead to the kidney results from effects on the cells lining the proximal tubules. Lead inhibits the metaboHc activation of vitamin D in these cells, and induces the formation of dense lead—protein complexes, causing a progressive destmction of the proximal tubules (13). Lead has been impHcated in causing hypertension as a result of a direct action on vascular smooth muscle as well as the toxic effects on the kidneys (12,13). 

Slow, R.C., Richards, J.P., PecHey, K.C., Leake, D.S., and Marm, G.E., 1999, Vitamin C protects human vascular smooth muscle cells against apoptosis induced by moderately oxidized LDL containing high levels of hpid hydroperoxides, Arterioscler. Thromb. 

Increases in plasma S-AA levels have previously been reported in patients with coronary disease (57). S-AA and plasma intracellular adhesion molecule-1 were elevated in patients with CAD and hyperhomocysteinemia, but only S-AA decreased after vitamin supplementation (35). Homocysteine activates nuclear factor- in endothelial cells, possibly via oxidative stress (58), and increases monocyte chemoattractant protein-1 expression in vascular smooth muscle cells (59). Additionally, it stimulates interleukin-8 expression in human endothelial cultures (60). These inflammatory factors are known to participate in the development of atherosclerosis. Taken together, these reports suggest an association of elevated tHcy and low-grade inflammation in CAD. 

Carmody et al. found that the addition of homocysteine to a culture of vascular smooth muscle cells resulted in a dose-dependent increase in DNA synthesis and cell proliferation, but vitamins B6 and B 2 alone did not substantially inhibit the effect of homocysteine. However, the addition of folic acid resulted in significant inhibition of DNA synthesis (64). Rosiglitazone has been shown to reduce serum tHcy levels, smooth muscle proliferation, and intimal hyperplasia in Sprague-Dawley rats fed a diet high in methionine (65). 

Intoxication with vitamin D causes weakness, nausea, loss of appetite, headache, abdominal pains, cramps, and diarrhea. More seriously, it also causes hypercalcemia, with plasma concentrations of calcium between 2.75 to 4.5 mmol per L, compared with the normal range of 2.2 to 2.5 mmol per L. At plasma concentrations of calcium above 3.75 mmol per L, vascular smooth muscle may contract abnormally, leading to hypertension and hypertensive encephalopathy. Hypercalciuria may also result in the precipitation of calcium phosphate in the renal tubules and hence the development of urinary calculi. Hypercalcemia can also result in calcinosis - the calcification of soft tissues, including kidneys, heart, lungs, and blood vessels. This is assumed to be the result of increased calcium uptake into tissues in response to excessive plasma concentrations of the vitamin and its metabolites. 

Increased uptake of calcium by arterial smooth muscle, leading to increased muscle tone, and hence increased circulatory resistance and blood pressure. This could reflect increased sensitivity of vascular smooth muscle to calcitriol (vitamin D) action in vitamin Bg deficiency the membrane calcium-binding protein is regulated by vitamin D, and vascular tissue has calcitriol receptors. 

Experiments in animals have found that proliferation of vascular smooth muscle cells can be inhibited by calcitriol administration (Mitsuhashi et al. 1991). An over-active renin-angiotensin system (RAS) can impair renal function and deteriorate cardiovascular health (Li 2012), and down-regulation of RAS activity is one of the key mechanisms proposed for calcitriol (Li et al. 2002). Evidence to support this mechanism has been primarily obtained from animal experiments for example, treatment with calcitriol has been shown to down-regulate RAS and to improve cardiac function in la-hydroxylase knockout mice (Zhou et al. 2008), and in salt-sensitive rats with cardiac hypertrophy (Bae et al. 2011, Choi et al. 2011). However, a recent randomized controlled trial in patients with chronic kidney disease did not find improvements in left ventricular mass index or diastolic function by treatment with paricalcitol (active vitamin D analogue) (Thadhani et al. 2012). 

The slow channel (L-type) is the major pathway by which Ca + enters the cell during excitation for initiation and regulation of the force of contraction of cardiac and skeletal muscle. Vascular smooth muscle also coutaius the L-type channel. The possibility that in the vitamin Bg-deficient hypertensive rat a higher concentration of cytosolic free Ca + might be responsible for the higher tension in the vascular smooth muscle was evaluated. In the deficient hypertensive rats the influx into the... 

Connective tissue in the vascular system plays an important role in maintenance of the intact vascular wall. Vitamins E and C influence the extracellular matrix (ECM) by their antioxidant functions. They bind to specific enzymes and act as cofactors and regulators with consequent modulation of vascular smooth muscle cell (VSMC) signal transduction and gene expression. The ability of vitamins E and C to influence VSMC proliferation, differentiation, and ECM production is important in the maintenance of intact vascular wall and in the repair of atherosclerotic lesions. Actively proliferating cells, but not quiescent cells, are susceptible to ascorbic acid, which inhibits cell division and promotes necrosis through its action on S-phase progression. 

Calcium play vital role in excitation - contraction coupling in myocardium. Calcium mediates contraction in vascular and other smooth muscles. Calcium is required for exocytosis and also involved in neurotransmitters release. Calcium also help in maintaining integrity of mucosal membranes and mediating cell adhesions. Hypercalcemia may occur in hyperthyroidism, vitamin D intoxication and renal insufficiency, which can be treated by administration of calcitonin, edetate sodium, oral phosphate etc. Hypocalcemia may occur in hypothyroidism, malabsorption, osteomalacia secondary to leak of vitamin D or vitamin D resistance, pancreatitis and renal failure. Hypocalcemia can be treated by chloride, gluconate, gluceptate, lactate and carbonate salts of calcium. 

The chemistry and biochemistry of the tocopherylquinones and tocopherols has been recently reviewed in some detail. The first recognized function of vitamin E was as an antisterility factor for the laboratory rat. However, it is now known to have multiple functions in vivo. For example, it is required for the maintenance of structural and functional integrity of skeletal, cardiac, and smooth muscle and, in some animals, the peripheral vascular system. Tocopherols also function as intracellular antioxidants, particularly with respect to the stabilization of ingested fats and perhaps products arising in the metabolic synthesis and degradation of lipids. It has also been proposed that the tocopherylquinones may have some functional role in electron transport systems. 

Slow, R. C., SATO, H., LEAKE, D. S.. ISHE, T., BANNAI, S. MANN, G. E. 1999b. Induction of antioxidant stress proteins in vascular endothehal and smooth muscle cells Protective action of vitamin C against atherogenic hpoproteins. Free Radio Res, 31, 309-18. 

ULRICH-MERZENICH, G METZNER, C SCHIERMEYER, B. VETTER, H. 2002. Vitamin C and vitamin E antagonistically modulate human vascular endothelial and smooth muscle cellDNA synthesis and proliferation. EurJ Nutr, 41, 27-34. 

The end result of centrally mediated sympathetic stimulation is an increase in peripheral resistance. This is reflected in elevations of both resting and stimulated vascular tone in the resistance arteries of the moderately vitamin Bg-deficient hypertensive rats. Elevated peripheral resistance is the hallmark of hypertension as seen in other models of hypertension. The increase in tone of caudal artery segmeuts from the hypertensive vitamin Bg-deficient rat is calcium depeudent. The decrease in tone following the addition to the medium of the calcium chaunel antagouist, uifed-ipine, indicates that the increased peripheral resistance resulting from increased permeability of smooth muscle plasma membraue to Ca + might be ceutral to the development of hypertension in the vitamin Bg-deficient rat. 

Nitric oxide (NO) produced by NO synthase in the endothelium is important in the maintenance of vascular tone it suppresses the expression of proinflammatory cytokines, adhesion molecules, and MCP-1. It also inhibits platelet adhesion, maintains the integrity of the arterial wall, and acts as an antioxidant. Vitamin E can reduce the inhibition of NO synthase by reactive oxygen species, thus maintaining NO production, either through its antioxidant activity or perhaps by suppressing PKC activity in smooth muscle. 

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