This article is part of a themed section on Redox Biology and Oxidative Stress in Health and Disease. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.12/issuetoc.

The objective of this study was to determine whether myogenic tone in the cerebral circulation can be modified by agents that interact with protein kinase C (PKC), a modulator of intracellular calcium sensitivity. Pial arteries (194±8 gtm at 125 mm Hg) were isolated from Wistar-Kyoto rats and mounted on glass microcannulas in a specialized arteriograph. Simultaneous recordings of transmural pressure and lumen diameter were made with a video-electronic system. Myogenic tone, which developed at transmural pressures above 50 mm Hg, reduced lumen diameter by 29±3%, to 136±5 ,um. Staurosporine (a PKC inhibitor) or indolactam (a PKC activator) was added cumulatively to segments of arteries obtained from each animal. Staurosporine induced progressive and eventually complete dilation, with half-maximal inhibition of myogenic tone occurring at a concentration of 1.32±0.10 nM. Conversely, indolactam augmented basal tone, reducing diameter by a maximum of 62 ±3%, with half-maximal effects at 0.4±1.0 ,M. The effects of indolactam on arterial responses to acute increases in transmural pressure were also determined to test whether this dynamic and possibly separate mechanism could be potentiated by PKC stimulation. Although basal tone was augmented, diameter responses to increased pressure were not altered. In summary, these results implicate PKC in the regulation of basal myogenic tone and resistance artery caliber, which is a major determinant of blood flow. PKC modulation did not affect diameter responses to sudden changes in transmural pressure, however, suggesting the existence of a separate sensing/transduction mechanism that has yet to be identified. (Circulation Research 1991; 68:359-367) B asal myogenic tone plays an important role in the physiological regulation of blood flow. When vascular smooth muscle is maintained in a state of partial activation, arterial diameter can be made to either increase or decrease, thereby facilitating blood flow regulation in a bidirectional fashion.' Observed most often in smaller arteries and arterioles, this state of maintained constriction is inherently dynamic, because the level of tone can be augmented by increasing pressure or stretch and thereby contribute to the autoregulation of blood flow.2-4 The cellular pathways underlying intrinsic tone are not well understood and involve transduction of physical forces into contractile filament activation through mechanisms that are dependent on From the

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 b...

Calorie restriction triggers a complex series of intricate events, including activation of cellular stress response elements, improved autophagy, modification of apoptosis, and alteration in hormonal balance. Intermittent fasting is not only more acceptable to patients, but it also prevents some of the adverse effects of chronic calorie restriction, especially malnutrition. There are many somatic and potentially psychologic benefits of fasting or intermittent calorie restriction. However, some behavioral modifications related to abstinence of binge eating following a fasting period are crucial in maintaining the desired favorable outcomes.

The prevalence of type-2 diabetes mellitus (T2DM) has increased dramatically during the last 2 decades, a fact driven by the increased prevalence of obesity, the primary risk factor for T2DM. The figures for diabetes in the Arab world are particularly startling as the number of people with diabetes is projected to increase by 96.2% by 2035. Genetic risk factors may play a crucial role in this uncontrolled raise in the prevalence of T2DM in the Middle Eastern region. However, factors such as obesity, rapid urbanization and lack of exercise are other key determinants of this rapid increase in the rate of T2DM in the Arab world. The unavailability of an effective program to defeat T2DM has serious consequences on the increasing rise of this disease, where available data indicates an unusually high prevalence of T2DM in Arabian children less than 18 years old. Living with T2DM is problematic as well, since T2DM has become the 5(th) leading cause of disability, which was ranked 10(th) as recently as 1990. Giving the current status of T2DM in the Arab world, a collaborative international effort is needed for fighting further spread of this disease.