Vasodilation, endothelium-dependent

In addition to the effects on blood lipids, it has been suggested that soy consumption has a beneficial action on arterial function and improves antioxidant status (Lichtenstein, 1998 and refs therein). Genistein and daidzein were shown to have antioxidant properties in vitro (Kerry and Abbey, 1998), to enhance endothelium-dependent vasodilation and to reduce the development of atherosclerosis in monkeys (Honore et al, 1997 Wagner et al, 1997). 

Chin et al. (1992) have su ested that oxidized LDL and high-density lipoprotein (HDL) inactivate endothelial cell-derived NO. NO inactivation was due to the oxidized lipids within the lipoprotein particles and was thought to be explained by a chemical reaction between the lipoproteins and NO. Other investigators have shown that relaxation of vascular smooth muscle by acetylcholine or bradykinin (endothelium-dependent vasodilators) is inhibited by LDL (Andrews etal., 1987). The role of NO in the modification of LDL is discussed in full detail in Chapter 2. 

Perticone F, Ceravolo R, Maio R, Ventura G, Zingone A, Perrotti N, Mat-tioli PL. Angiotensin-converting enzyme gene polymorphism is associated with endothelium-dependent vasodilation in never treated hypertensive patients. Hypertension 1998 31 900-905. 

P2Y receptors that are found on endothelial cells elicit a Ca2+-dependent release of endothelium-dependent relaxing factor (EDRF) and vasodilation. A secondary activation of a Ca2+-sensitive phospholipase A2 increases the synthesis of endothelial prostacyclin, which limits the extent of intravascular platelet aggregation following vascular damage and platelet stimulation. The P2Y-mediated vasodilation opposes a vasoconstriction evoked by P2X receptors located on vascular smooth muscle cells. The latter elicit an endothelial-independent excitation (i.e. constriction). P2Y receptors are also found on adrenal chromaffin cells and platelets, where they modulate catecholamine release and aggregation respectively. 

Mixed evidence, however, has been described in women. Raloxifene improved flow-mediated, endothelium-dependent vasodilation in postmenopausal women (Sarrel et al. 2003) to an extent similar to that of HT (Colacurci et al. 2003 Saitta et al. 2001). Other investigators, however, have been unable to detect any effect of raloxifene (Ceresini et al. 2003 Griffiths et al. 2003). Flow-mediated vasodilation has been described for droloxifene (Herrington et al. 2000), while a neutral effect on vascular reactivity has been described for ospemifene, a more recent SERM (Ylikorkala et al. 2003). 

Ceresini G, Marchini L, Rebecchi I, Morganti S, Bertone L, Montanari I, Bacchi-Modena A, Sgarabotto M, Baldini M, Denti L, Ablondi F, Ceda GP, Valenti G (2003) Effects of raloxifene on carotid blood flow resistance and endothelium-dependent vasodilation in postmenopausal women. Atherosclerosis 167 121-127... 

Saitta A, Altavilla D, Cucinotta D, Morabito N, Frisina N, Corrado F, D Anna R, Lasco A, Squadrito G, Gaudio A, Cancellieri F, Arcoraci V, Squadrito F (2001) Randomized, double-blind, placebo-controlled study on effects of raloxifene and hormone replacement therapy on plasma no concentrations, endothelin-1 levels, and endothelium-dependent vasodilation in postmenopausal women. Arterioscler Thromb Vase Biol 21 1512-1519... 

Dysregulation of the vascular endothelium has emerged as a critical component of most thrombotic disorders [10, 21]. Often without any anatomical sign of atherosclerosis, many cardiovascular diseases express a vasomotor abnormality termed endothelial dysfunction, indexed clinically as impaired endothelium-dependent vasodilation [31]. Although its mechanism is multifactorial, endothelial dysfunction is characterized by diminished vascular NO production and/or bioavailability [32]. The... 

The anandamide precursor, phosphatidylethanol amine, is present in membranes almost always accompanied by phophatidylserine. It seemed reasonable to expect the formation of anandamide from its precursor will be paralleled by formation of N-arachidinoylserine from phosphatidyl serine. Indeed, A -arachidonoyl-L-serine (ARA-S) was found to be formed alongside anandamide (Fig. 4). This compound was isolated from bovine brain and its structure was elucidated by comparison with synthetic ARA-S. Contrary to anandamide, ARA-S binds very weakly to the known cannabinoid CBi and CB2 or vanilloid TRPVl receptors. However, it produces endothelium-dependent vasodilation of rat isolated mesenteric... 

NO has a significant effect on vascular smooth muscle tone and blood pressure. Numerous endothelium-dependent vasodilators, such as acetylcholine and bradykinin, act by increasing intracellular calcium levels, which induces NO synthesis (Figure 19-2). Mice with a knockout mutation in the eNOS gene display increased vascular tone and elevated mean arterial pressure, indicating that eNOS is a fundamental regulator of blood pressure. The effects of vasopressor drugs are increased by inhibition of NOS. 

Grassi D, Necozione S, Lippi C, Croce G, Valeri L, Pasqualetti P, Desideri G, Blumberg JB, Ferri C. 2005b. Cocoa reduces blood pressure and insulin resistance and improves endothelium-dependent vasodilation in hypertensives. Hypertension 46 398 -05. 

Homocysteine decreases the bioavailability of nitrous oxide (NO) via a mechanism involving glutathione peroxidase (37). Tawakol et al. (38) reported that hyperhomocysteinemia is associated with impaired endothelium-dependent vasodilation in humans. Homocysteine impairs the NO synthase pathway both in cell culture (39) and in monkeys with hyperhomocysteinemia, by increasing the levels of asymmetric dimethylarginine (ADMA), an endogenous NO synthase inhibitor (40). Elevation of ADMA may mediate endothelial dysfunction during experimental hyperhomocysteinemia in humans (41). However, Jonasson et al. (42) did not find increased ADMA levels in patients with coronary heart disease and hyperhomocysteinemia, nor did vitamin supplementation have any effect on ADMA levels in spite of substantial plasma tHcy reduction,... 

Tawakol A, et al. Hyperhomocyst(e)inemia is associated with impaired endothelium-dependent vasodilation in humans, Circulation 1997 95(5) I I 19-1 121. 

Higashi Y, Kimura M, Hara K, et al. Autologous bone-marrow mononuclear cell implantation improves endothelium-dependent vasodilation in patients with limb ischemia. Circulation 2004 109 1215-1218. 

Kaiser DR, Billups K, Mason C, et al, Impaired brachial artery endothelium-dependent and -independent vasodilation in men with erectile dysfunction and no other clinical cardiovascular disease, J Am Coll Cardiol 2004 43 (2) 179-1 84,... 

Ghayurefo/. (2005)reportedthe hypotensive, endothelium-dependent and -independent vasodilator and cardio-suppressant and stimulant effects of aqueous extract (Zo. Cr) of ginger. Zo.Cr, which tested positive for saponins, flavonoids, amines, alkaloids and terpenoids, induced a dose-dependent... 

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