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1. Endothelial cells have a key role in the cardiovascular system. Most endothelial cell functions depend on changes in cytosolic Ca2+ concentrations ([Ca2+]i) to some extent and Ca2+ signalling acts to link external stimuli with the synthesis and release of regulatory factors in endothelial cells. The [Ca2+]i is maintained by a well-balanced Ca2+ flux across the endoplasmic reticulum and plasma membrane. 2. Cyclic nucleotides, such as cAMP and cGMP, are very important second messengers. The cyclic nucleotides can affect [Ca2+]i directly or indirectly (via the actions of protein kinase (PK) A or PKG-mediated phosphorylation) by regulating Ca2+ mobilization and Ca2+ influx. Fine-tuning of [Ca2+]i is also fundamental to protect endothelial cells against damaged caused by the excessive accumulation of Ca2+. 3. Therapeutic agents that control cAMP and cGMP levels have been used to treat various cardiovascular diseases. 4. The aim of the present review is to discuss: (i) the functions of endothelial cells; (ii) the importance of [Ca2+]i in endothelial cells; (iii) the impact of excessive [Ca2+]i in endothelial cells; and (iv) the balanced control of [Ca2+]i in endothelial cells via involvement of cyclic nucleotides (cAMP and cGMP) and their general effectors. [ABSTRACT FROM AUTHOR]

There is much evidence extolling the virtues of physical activity on cardiovascular disease (CVD). The evidence derives from different population groups where leisure time physical activity reduced the risk of coronary heart disease and cardiovascular mortality in both men and women. Recent meta-analyses have shown that large risk reductions for both ischaemic and haemorrhagic stroke can be achieved by moderate or intense physical activity. There are many data from human and animal studies confirming a beneficial role for exercise in the prevention and treatment of CVD. Physical inactivity and obesity/overweight are not only associated with a number of health-related risk factors, but are considered to be independent risk factors for CVD, type 2 diabetes mellitus and hypertension. Clinical trials confirm that lifestyle interventions (dietary modification and increased physical activity) reduce the risk of progressing from impaired glucose tolerance to type 2 diabetes. Moreover, epidemiological studies indicate that the risk of hypertension increases by being overweight. Modest increases in exercise intensity and frequency have hypotensive effects in sedentary hypertensive patients. Long-term training improves endothelium-dependent dilatation in the aorta and resistance arteries of the heart, whereas short-term training increases endothelial function in coronary conduit arteries. Overall, more scientific evidence will undoubtedly encourage the widespread advocacy of the clinical benefits of exercise therapy in the prevention and treatment of CVD. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) remains the leading cause of morbidity and premature mortality in both women and men in most industrialized countries, and has for some time also established a prominent role in developing nations. In fact, obesity, diabetes mellitus and hypertension are now commonplace even in children and youths. Regular exercise is rapidly gaining widespread advocacy as a preventative measure in schools, medical circles and in the popular media. There is overwhelming evidence garnered from a number of sources, including epidemiological, prospective cohort and intervention studies, suggesting that CVD is largely a disease associated with physical inactivity. A rapidly advancing body of human and animal data confirms an important beneficial role for exercise in the prevention and treatment of CVD. In Part 1 of this review we discuss the impact of exercise on CVD, and we highlight the effects of exercise on (i) endothelial function by regulation of endothelial genes mediating oxidative metabolism, inflammation, apoptosis, cellular growth and proliferation, increased superoxide dismutase (SOD)-1, down-regulation of p67phox, changes in intracellular calcium level, increased vascular endothelial nitric oxide synthase (eNOS), expression and eNOS Ser-1177 phosphorylation; (ii) vascular smooth muscle function by either an increased affinity of the Ca2+ extrusion mechanism or an augmented Ca2+ buffering system by the superficial sarcoplasmic reticulum to increase Ca2+ sequestration, increase in K+ channel activity and/or expression, and increase in L-type Ca2+ current density; (iii) antioxidant systems by elevation of Mn-SOD, Cu/Zn-SOD and catalase, increases in glutathione peroxidase activity and activation of vascular nicotinamide adenine dinucleotide phosphate [(NAD(P)H] oxidase and p22phox expression; (iv) heat shock protein (HSP) expression by stimulating HSP70 expression in myocardium, skeletal muscle and even in human leucocytes, probably through heat shock transcription factor 1 activity; (v) inflammation by reducing serum inflammatory cytokines such as high-sensitivity C-reactive protein (hCRP), interleukin (IL)-6, IL-18 and tumour necrosis factor-alpha and by regulating Toll-like receptor 4 pathway. Exercise also alters vascular remodelling, which involves two forms of vessel growth including angiogenesis and arteriogenesis. Angiogenesis refers to the formation of new capillary networks. Arteriogenesis refers to the growth of pre-existent collateral arterioles leading to formation of large conductance arteries that are well capable to compensate for the loss of function of occluded arteries. Another aim of this review is to focus on exercise-related cardiovascular protection against CVD and associated risk factors such as aging, coronary heart disease, hypertension, heart failure, diabetes mellitus and peripheral arterial diseases mediated by vascular remodelling. Lastly, this review examines the benefits of exercise in mitigating pre-eclampsia during pregnancy by mechanisms that include improved blood flow, reduced blood pressure, enhanced placental growth and vascularity, increased activity of antioxidant enzymes, reduced oxidative stress and restored vascular endothelial dysfunction. [ABSTRACT FROM AUTHOR]