Cardiovascular disease vascular effect

N. de Rons, Trans fatty acids, HDL-cholesterol, and cardiovascular disease risk Effects of dietary changes on vascular reactivity, Wageningen Universiteit, Wageningen, the Netherlands, 2001. 

Cardiovascular disease (CVD) is characterized by the involvement of the heart and allied vascular system. High cholesterol, associated lipid abnormahties and high blood pressure are recognized as the major risk factors of CVD. There have been several animal experiments and clinical studies using rice bran and rice bran oil, which have demonstrated a hypocholesterolemic effect (Raghuram et al., 1989 Rukmini and Raghuram, 1991 Sugano and Tsuji, 1997). The mechanisms involved are briefly summarized. 

The vascular endothelium produces a number of substances that are released basally into the blood vessel wall to alter vascular smooth muscle tone. One such substance is endothelin (ET-1). Endothelin exerts its effects throughout the body, causing vasoconstriction as well as positive inotropic and chronotropic effects on the heart. The resulting increases in TPR and CO contribute to an increase in MAP. Synthesis of endothelin appears to be enhanced by many stimuli, including Ag II, vasopressin, and the mechanical stress of blood flow on the endothelium. Synthesis is inhibited by vasodilator substances such as prostacyclin, nitric oxide, and atrial natriuretic peptide. There is evidence that endothelin is involved with the pathophysiology of many cardiovascular diseases, including hypertension, heart failure, and myocardial infarction. Endothelin receptor antagonists are currently available for research use only. 

Although ketamine produces direct myocardial depression, it has significant indirect cardiovascular effects through sympathomimetic effects and stimulation of the vasomotor centre. The heart rate and systolic blood pressure increase by 30% and occasionally up to 100%. Owing to the increased cardiac work and myocardial consumption, ketamine adversely affects the balance between myocardial oxygen supply and demand. Consequently, it is not recommended for use as the sole agent in adults with severe cardiovascular disease. However, the same haemodynamic effects, particularly the raised systemic vascular resistance, make the agent particularly suitable for children with cyanotic heart disease. 

NO also reduces endothelial adhesion of monocytes and leukocytes, key features of the early development of atheromatous plaques. This effect is due to the inhibitory effect of NO on the expression of adhesion molecules on the endothelial surface. In addition, NO may act as an antioxidant, blocking the oxidation of low-density lipoproteins and thus preventing or reducing the formation of foam cells in the vascular wall. Plaque formation is also affected by NO-dependent reduction in endothelial cell permeability to lipoproteins. The importance of eNOS in cardiovascular disease is supported by experiments showing increased atherosclerosis in animals deficient in eNOS by pharmacologic inhibition. Atherosclerosis risk factors, such as smoking, hyperlipidemia, diabetes, and hypertension, are associated with decreased endothelial NO production, and thus enhance atherogenesis. 

Another potential mechanism by which flavonoids may be protective in cardiovascular diseases is by their direct effects on vascular smooth muscle cells either as vasodilators or as inhibitors of proliferation. However, vasoconstrictor effects have also been reported for some flavonoids. 

Estrogens have also been found to have direct effects on blood vessels, including increased synthesis of nitric oxide and increased vasodilation (Farhat et al., 1996 McCrohon et al., 1996). The observed decrease in the risk of cardiovascular disease and atherosclerosis by estrogens (Pines et al, 1997 Punnonen et al., 1995 Stampfer and Colditz, 1991) is thought to be due to the combined effects of estrogens on serum lipids and vascular reactivity. 

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