Endothelial Regulation of Vascular Tone and Growth

The endothelium regulates vascular tone by releasing factors involved in relaxation and contraction, in coagulation and thrombus formation, and in growth inhibition and stimulation. Endothelium-dependent relaxations are elicited by transmitters, hormones, platelet substances, and the coagulation system, and by physical stimuli such as the shear stress from circulating blood. They are mediated by the endothelium-derived relaxing factor, recently identified as nitric oxide, which causes vasodilation and platelet deactivation. Other proposed endothelium- derived relaxing factors include a hyperpolarizing factor, lipooxygenase products, and the cytochrome P450 pathway. Endothelium-derived contracting factors are produced by the cyclooxygenase pathway and by endothelial cells, which produce the peptide endothelin-1, a potent vasoconstrictor that under normal conditions circulates at low levels. The endothelium produces both growth inhibitors— normally dominant—and growth stimuli. Denuded or dysfunctional endothelium leads to a proliferative response and intimal hyperplasia in the vessel wall; moreover, platelets adhere to the site and release potent growth factors. Endothelial dysfunction has numerous causes: Aging is associated with increased formation of contracting factor and decreased relaxing factor; denudation, such as by coronary angioplasty, impairs the capacities of regenerated endothelial cells; oxidized low-density lipoproteins and hypercholesterolemia interfere with nitric oxide production; hypertension morphologically and functionally alters the endothelium; and atherosclerosis markedly attenuates some endothelium- dependent relaxations. For patients with coronary bypass grafts, differences in endotheliumderived vasoactive factors between the internal mammary artery and the saphenous vein may be important determinants of graft function, with the mammary artery having more pronounced relaxations than the saphenous vein and thus a higher patency rate. Am J Hypertens 1993;6:283S-293

The Year in Cardiology 2013: imaging in ischaemic heart disease

This article focuses on some of the most important studies published in the year 2013 in cardiac imaging related to ischemic heart disease. Many of the studies across the various imaging techniques addressed the prognostic impact of imaging data on outcome in patients with this diseas

P-576: Differential effects of selective cyclooxygenase-2 inhibitors on endothelial function in salt-induced hypertension

In view of the ongoing controversy of potential differences in cardiovascular safety of selective COX-2 inhibitors (coxibs), we compared the effects of two different coxibs and a traditional NSAID on endothelial dysfunction, a well established surrogate of cardiovascular disease, in salt-induced hypertension. Salt-sensitive (DS) and salt-resistant (DR) Dahl rats were treated with a high-sodium diet (4% NaCl) for 56 days. From days 35 to 56, diclofenac (6 mg/kg/d; DS-diclofenac), rofecoxib (2 mg/kg/d; DS-rofecoxib), celecoxib (25 mg/kg/d; DS-celecoxib) or placebo (DS-placebo) were added to the chow. Vascular reactivity of isolated aortic rings was assessed by isometric tension recording. Blood pressure increased with high sodium diet in the DS-groups which was more pronounced after diclofenac and rofecoxib treatment (p<0.005 vs DS-placebo), but slightly blunted by celecoxib (p<0.001 vs DS-placebo). Sodium diet markedly reduced NO-mediated endothelium-dependent relaxations to acetylcholine (ACh, 10−10−10−5 mol/L) in untreated hypertensive rats (p<0.0001 vs DR-placebo). Relaxation to ACh improved after celecoxib (p<0.005 vs DS-placebo and DS-rofecoxib), but remained unchanged after rofecoxib and diclofenac treatment. Vasoconstriction after NOS inhibition with Nω-Nitro-L-Arginine Methyl Ester (10-4 mol/L) was blunted in DS rats (p<0.05 vs DR-placebo), normalized by celecoxib, but not affected by rofecoxib or diclofenac. Protein expression of eNOS was decreased in DS rats with a trend for increased eNOS levels in the DS-celecoxib group (97.8±25.6 vs 54.8±2.8 %, p=0.088 vs DS-placebo). Indicators of oxidative stress, 8-isoprostane levels, were elevated in untreated DS rats on 4% NaCl (6.55±0.58 vs 3.65±1.05 ng/ml, p<0.05) and normalized by celecoxib only (4.29±0.58 ng/ml), while SOD protein expression was decreased in DS rats and not affected by any treatment. Plasma levels of prostaglandines did not change during high sodium diet or any treatment. These data show that celecoxib, but not rofecoxib or diclofenac, improves endothelial dysfunction and reduces oxidative stress, thus pointing to differential effects of coxibs in salt-sensitive hypertension. Am J Hypertens (2004) 17, 243A-243A; doi: 10.1016/j.amjhyper.2004.03.65