Nutritional effects on blood pressure

PURPOSE OF REVIEW: There has not been a thorough recent evaluation of the nutritional effects on blood pressure. Apart from outstanding clinical trials like Dietary Approaches to Stop Hypertension, there have been controversial papers on a number of factors influencing blood pressure. This paper is a systematic review of the current literature as it relates to hypertension. RECENT FINDINGS: Results from many meta-analyses and well controlled clinical trials on the effects of a variety of nutritional factors are presented in this review. Evidence suggests that dietary sodium intake needs reduction. There is a seemingly inverse relationship between protein intake and blood pressure, but data are inconclusive. High monounsaturated fat and fish oil appear to be beneficial. Several studies on dietary fiber indicate that the strongest evidence for blood pressure lowering effects is in hypertensive as opposed to normotensive participants. Vegetarians seem to have lower levels of hypertension and cardiovascular disease risk. Low carbohydrate diets show short-term beneficial effects but are not sustained. High levels of potassium, magnesium, calcium and soy seem to have some benefit, but results remain inconclusive. Weight reduction positively impacts blood pressure. SUMMARY: More compelling research defining specific factors is needed to inform the public as to steps needed to reduce blood pressure and improve cardiovascular risk.     

Debate: Does it matter how you lower blood pressure?

Whether it matters how pressure is lowered has been debated since antihypertensive drugs proved to prevent cardiovascular events. However, in clinical trials, while the stroke benefit predicted by a given difference in blood pressure was achieved, the results for myocardial infarction were roughly half that expected. This suggested that adverse drug effects of diuretics and β-blockers might have detracted from their hypotensive effects. Trials with newer antihypertensive classes have revealed superior effects on outcomes associated with converting enzyme inhibitor use, and that α-blockers are less cardioprotective than diuretics. These studies establish that simple blood pressure reduction is an inadequate guide to therapy. The challenge now will be to determine the optimal therapy for each hypertensive patient.     

Nitric oxide and atherosclerosis: an update.

Nitric oxide (NO) is a molecule that has gained recognition as a crucial modulator of vascular disease. NO has a number of intracellular effects that lead to vasorelaxation, endothelial regeneration, inhibition of leukocyte chemotaxis, and platelet adhesion. Endothelium damage induced by atherosclerosis leads to the reduction in bioactivity of endothelial NO synthase (eNOS) with subsequent impaired release of NO together with a local enhanced degradation of NO by increased generation of reactive oxygen species with subsequent cascade of oxidation-sensitive mechanisms in the arterial wall. Many commonly used vasculoprotective agents have their therapeutic actions through the production of NO. L-Arginine, the precursor of NO, has demonstrated beneficial effects in atherosclerosis and disturbed shear stress. Finally, eNOS gene polymorphism might be an additional risk factor that may contribute to predict cardiovascular events. However, further studies are needed to understand the possible clinical implications of these correlations.     

The evolutionary and ecological benefits of asteroid and comet impacts

Commonly viewed solely as agents of destruction, asteroid and comet impact events can also have a beneficial influence on processes from the molecular to the evolutionary scale. On the heavily bombarded early Earth, impacts might have delivered and caused the synthesis of prebiotic compounds that eventually led to life. At the organismal and ecosystem level, impact events can provide new habitats through the shock processing of target materials and by enhancing water availability, such as within intracrater lakes. At the evolutionary level, by destroying entire groups of organisms, impacts might have been instrumental in enabling the rise of new groups, such as the dinosaurs and mammals. Here, we synthesize the emerging literature on the beneficial effects of impacts to provide a novel perspective on these extraterrestrial agents of biological change.     

Increased hair selenium concentration in hyperlipidemic patients

Selenium is an essential trace element with potential anti‐atherogenic and antioxidant effects. Experimental data suggest that selenium might be beneficial in the prevention of atherosclerosis and its complications, whereas human epidemiological studies have yielded conflicting results. Data on hair selenium status in hyperlipidemic patients are still lacking. Therefore, we analysed selenium concentrations by X‐ray fluorescence in the hair of 81 statin‐naïve patients with newly diagnosed Fredrickson‐type IIa and IIb hyperlipoproteinemia and compared their data with 43 healthy volunteers. We also assessed the frequency of other classical risk factors of atherosclerosis. Hair selenium levels were found to be significantly higher in hyperlipidemic patients compared with volunteers with normal lipid levels. Also, a significantly increased number of traditional atherosclerosis risk factors were observed in hyperlipidemic patients with hair selenium concentrations above the median in contrast to those with below. Our results suggest that high hair selenium status might be associated with adverse blood lipid profile together with an increased number of traditional risk factors in a selenium‐deplete population. These findings warrant further investigations to study the impact of selenium supplementation on the incidence of cardiovascular events.     

Calcium Channel Blocker Enhances Beneficial Effects of an Angiotensin II AT1 Receptor Blocker against Cerebrovascular-Renal Injury in type 2 Diabetic Mice

Recent clinical trials have demonstrated that combination therapy with renin-angiotensin system inhibitors plus calcium channel blockers (CCBs) elicits beneficial effects on cardiovascular and renal events in hypertensive patients with high cardiovascular risks. In the present study, we hypothesized that CCB enhances the protective effects of an angiotensin II type 1 receptor blocker (ARB) against diabetic cerebrovascular-renal injury. Saline-drinking type 2 diabetic KK-A^y mice developed hypertension and exhibited impaired cognitive function, blood-brain barrier (BBB) disruption, albuminuria, glomerular sclerosis and podocyte injury. These brain and renal injuries were associated with increased gene expression of NADPH oxidase components, NADPH oxidase activity and oxidative stress in brain and kidney tissues as well as systemic oxidative stress. Treatment with the ARB, olmesartan (10 mg/kg/day) reduced blood pressure in saline-drinking KK-A^y mice and attenuated cognitive decline, BBB disruption, glomerular injury and albuminuria, which were associated with a reduction of NADPH oxidase activity and oxidative stress in brain and kidney tissues as well as systemic oxidative stress. Furthermore, a suppressive dose of azelnidipine (3 mg/kg/day) exaggerated these beneficial effects of olmesartan. These data support the hypothesis that a CCB enhances ARB-associated cerebrovascular-renal protective effects through suppression of NADPH oxidase-dependent oxidative stress in type 2 diabetes.     

Intrauterine programming of hypertension: the role of the renin-angiotensin system

From experiments with prenatal undernutrition in the rat, it is clear that fetal exposure to glucocorticoids of maternal origin is a key first step in the programming of hypertension and perhaps coronary heart disease. The chain of events leading from glucocorticoid action in the fetal tissues to hypertension in adulthood involves the development of hypersensitivity to glucocorticoids in adult life (Scheme 1). This has the effect of activating the RAS through induction of key genes such as ACE, which, in turn, may increase sensitivity of the blood vessels to the actions of ANGII. Another consequence of prenatal undernutrition, which may or may not involve glucocorticoids, is the abnormal development of the kidney [35]. Impaired nephrogenesis must surely have an impact upon lifelong renal function and cardiovascular control. Progress has been made in demonstrating that hypertension can be prenatally programmed through maternal dietary manipulation and some of the putative mechanisms involved have been identified. The priorities in this field of research must now be to clarify the role of maternal diet as a programming stimulus in order to generate an effective series of public health guidelines for pregnant women. Although the identification of metabolic mechanisms might suggest possible pharmacological interventions in early life as a means of reducing cardiovascular risk in adult life [49], it will always be more desirable to optimize maternal diet.     

Conjugated linoleic acid: effects on plasma lipids and cardiovascular function

Conjugated linoleic acid is a collective name for mixtures of several positional and geometric conjugated dienoic isomers of linoleic acid, which have been shown to impact favorably on several biological processes, particularly carcinogenesis. Recent studies have clearly established that the c9, t11 and t10, c12 isomers have distinct biological effects. The latter may be of particular importance in affecting blood lipids. Because conjugated linoleic acid has been suggested to be anti-atherogenic, this review is focused on its effects on cardiovascular function. Careful scrutiny of the literature suggests that at present it is premature to assign any beneficial role to conjugated linoleic acid in terms of its ability to impact either blood lipids or atherogenesis.     

Pleiotropic effects of statin therapy: molecular mechanisms and clinical results

Statins inhibit the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, which is required for cholesterol biosynthesis, and are beneficial in the primary and secondary prevention of cardiovascular disease. Most of the benefits of statin therapy are owing to the lowering of serum cholesterol levels. However, by inhibiting HMG-CoA reductase, statins can also inhibit the synthesis of isoprenoids, which are important lipid attachments for intracellular signaling molecules, such as Rho, Rac and Cdc42. Therefore, it is possible that statins might exert cholesterol-independent or 'pleiotropic' effects through direct inhibition of these small GTP-binding proteins. Recent studies have shown that statins might have important roles in diseases that are not mediated by cholesterol. Here, we review data from recent clinical trials that support the concept of statin pleiotropy and provide a rationale for their clinical importance.     

ACE inhibition and atherogenesis

Recent clinical studies such as HOPE, SECURE, and APRES show that angiotensin-converting enzyme (ACE) inhibitors like ramipril improve the prognosis of patients with a high risk of atherothrombotic cardiovascular events. Atherosclerosis, as a chronic inflammatory condition of the vascular system, can turn into an acute clinical event through the rupture of a vulnerable atherosclerotic plaque followed by thrombosis. ACE inhibition has a beneficial effect on the atherogenic setting and on fibrinolysis. Endothelial dysfunction is the end of a common process in which cardiovascular risk factors contribute to inflammation and atherogenesis. By inhibiting the formation of angiotensin II, ACE inhibitors prevent any damaging effects on endothelial function, vascular smooth muscle cells, and inflammatory vascular processes. An increase in the release of NO under ACE inhibition has a protective effect. Local renin-angiotensin systems in the tissue are involved in the inflammatory processes in the atherosclerotic plaque. Circulating ACE-containing monocytes, which adhere to endothelial cell lesions, differentiate within the vascular wall to ACE-containing macrophages or foam cells with increased local synthesis of ACE and angiotensin II. Within the vascular wall, angiotensin II decisively contributes to the instability of the plaque by stimulating growth factors, adhesion molecules, chemotactic proteins, cytokines, oxidized LDL, and matrix metalloproteinases. Suppression of the increased ACE activity within the plaque can lead to the stabilization and deactivation of the plaque by reducing inflammation in the vascular wall, thus lessening the risk of rupture and thrombosis and the resultant acute clinical cardiovascular events. The remarkable improvement in the long-term prognosis of atherosclerotic patients with increased cardiovascular risk might be the clinical result of the contribution made by ACE inhibition in the vascular wall.     

Beneficial effects of Provinols: cardiovascular system and kidney

Red wine polyphenols have been reported to exert beneficial effects in preventing cardiovascular diseases but their molecular mechanisms of hemodynamic effects on functional cardiovascular and renal changes were studied much less. The review is focused on in vitro as well as in vivo effects of red wine extract containing polyphenolic compounds (Provinols) on cardiovascular systems and kidney in relation to the molecular and biochemical mechanisms of these compounds. This review provides the evidence that Provinols is able to produce ex vivo endothelium-dependent relaxation as a result of enhanced NO synthesis. Administration of Provinols partially prevents the development of hypertension during NO deficiency and accelerates the decrease of blood pressure in already established hypertension. The effects of Provinols include prevention and/or attenuation of myocardial fibrosis, reduction of aortic wall thickening and improvement of vascular functions. These functional and structural alterations are associated with significant augmentation of NO production, seen as the increase of NO synthase activity and eNOS protein expression. Moreover, it has been documented that Provinols decreased the oxidative stress within the cardiovascular system and kidney.     

Anti-atherosclerotic and anti-diabetic properties of probucol and related compounds

Probucol is a diphenolic compound with anti-oxidant and anti-inflammatory properties that reduces atherosclerosis and restenosis. Unfortunately, adverse effects on blood lipoproteins and cardiac electrophysiology have curtailed its use as a drug. Compounds related to probucol that have improved efficacy without the adverse effects offer promise as novel therapies of cardiovascular disease. Recent results suggest that these compounds may be used for the prevention of type 2 diabetes, a disease that is increasing in prevalence and importance world-wide. In this review, the molecular mechanisms underlying the beneficial activities of probucol and related compounds are described.     

Structure-based optimization of cyclopropyl urea derivatives as potent soluble epoxide hydrolase inhibitors for potential decrease of renal injury without hypotensive action

Epoxyeicosatrienoic acids (EETs) are known to have beneficial pharmacological effects on various cardiovascular events. However, EETs are biologically metabolized by soluble epoxide hydrolase (sEH) to less active metabolites. In our search for potent sEH inhibitors, we optimized a series of cyclopropyl urea derivatives and identified compound 38 as a potent sEH inhibitor with minimal CYP inhibition and good oral absorption in rats. Administration of 38 to DOCA-salt rats suppressed urinary albumin and MCP-1 excretion without affecting systolic blood pressure.     

Cardiovascular pleiotropic actions of DPP-4 inhibitors: A step at the cutting edge in understanding their additional therapeutic potentials

Dipeptidyl peptidase 4 (DPP-4) is a serine protease enzyme expressed widely in many tissues, including the cardiovascular system. The incretin hormones such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are released from the small intestine into the vasculature during a meal, and these incretins have a potential to release insulin from pancreatic beta cells of islets of Langerhans, affording a glucose-lowering action. However, both incretins are hurriedly degraded by the DPP-4. Inhibitors of DPP-4, therefore, enhance the bioavailability of GLP-1 and GIP, and thus have been approved for better glycemic management in patients afflicted with type 2 diabetes mellitus (T2DM). Five different DPP-4 inhibitors, often called as ‘gliptins’, namely sitagliptin, vildagliptin, saxagliptin, linagliptin and alogliptin have been approved hitherto for clinical use. These drugs are used along with diet and exercise to lower blood sugar in diabetic subjects. T2DM is intricately related with an increased risk of cardiovascular disease. Growing body of evidence suggests that gliptins, in addition to their persuasive anti-diabetic action, have a beneficial pleiotropic action on the heart and vessels. In view of the fact of cardiovascular disease susceptibility of patients afflicted with T2DM, gliptins might offer additional therapeutic benefits in treating diabetic cardiovascular complications. Exploring further the cardiovascular pleiotropic potentials of gliptins might open a panorama in impeccably employing these agents for the dual management of T2DM and T2DM-associated perilous cardiovascular complications. This review will shed lights on the newly identified beneficial pleiotropic actions of gliptins on the cardiovascular system.     

Rosiglitazone inhibits endothelial proliferation and angiogenesis

Rosiglitazone, an insulin sensitizer, is known to offer beneficial effects in retarding atherosclerotic vascular diseases. Since proliferation and angiogenesis are involved in initiation and plaque instability, two critical steps in the cardiovascular events, this study was designed to evaluate the mechanisms of rosiglitazone on endothelial proliferation and angiogenesis. Rosiglitazone-treated human umbilical vein endothelial cells were analyzed for growth rate by use of cell number counting, 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay as well as 3H-thymidine incorporation. Cell cycle analysis was detected by flow cytometry and cell cycle-related proteins were measured by Western blot. Effects of rosiglitazone on angiogenesis were assessed by vascular endothelial growth factor (VEGF)-induced tube formation and wound-healing migration. Furthermore, effects of rosiglitazone on actin stress fiber were observed under confocal microscopy. Our data showed that rosiglitazone inhibits endothelial proliferation in a dose-dependent manner. Rosiglitazone caused endothelial arrest at G1 phase via affecting several cell cycle-related proteins that led to attenuate phosphorylation of retinoblastoma protein. Rosiglitazone markedly decreased VEGF-induced tube formation and endothelial cell migration, which might be explained by a disorganization of the actin cytoskeleton. Our data suggest that both anti-proliferative and anti-angiogenic activities in endothelial cells might account for the greater than expected beneficial effects of rosiglitazone for the treatment and prevention of atherosclerosis.     

Vibration training: benefits and risks

The main results of our recent several studies, i.e. the measurements of vibration training results for single case and group studies as well as the cardiovascular parameter measurements during vibrations and the corresponding hydrodynamic analysis, are summarized. Our studies and previous work all confirm that vibration training is an effective training method in order to improve maximal strength and flexibility as well as various other factors if the training is properly designed. Some recommendations regarding the proper ranges of frequencies, amplitudes and exposure duration of vibration training are made based on the existing vibration training practice and mechanism analysis, although much work remains to be carried out in order to set up clear rules for various groups of people so that maximal training results could be expected and in the meantime potential dangerous effects could be avoided. Cardiovascular parameter measurements confirm that total peripheral resistance (TPR) to the blood flow is increased during body vibration. Hydrodynamic analysis offers the mechanism for the increase of TPR through the deformation of vessels. As a reaction of compensation, more capillaries are probably opened in order to keep a necessary level of cardiac output needed for the body, resulting in more efficient gas and material metabolism between the blood and muscle fibres. This might be one of the reasons for the various potential beneficial effects of vibration training.     

Effects of resveratrol and other wine polyphenols on vascular function: an update

Several epidemiologic observations show that moderate wine drinking reduces cardiovascular morbidity and mortality. Wine contains several polyphenols, and among them, resveratrol in particular has been shown to exert a number of important biologic activities on the cardiovascular system that may contribute to the protective effects of wine. The mechanisms through which resveratrol and other wine polyphenols protect from ischemic cardiovascular events are many, but protection from oxidative stress and radical oxygen species production, a facilitating activity on nitric oxide production and activity and the ability to modulate the expression of adhesive molecules by blood cells and the vascular wall seem to be the most important. In this overview, the in vitro and in vivo evidence on the activity of resveratrol on vascular function and circulating blood cells, with a special emphasis on blood platelets, is thoroughly presented.     

Statins – Do we really know all mechanisms of action of this group of drugs?

The role of statins in the treatment and prevention of cardiovascular diseases, such as coronary artery disease, acute coronary syndromes, diabetes or stroke is well established. However, there are still many questions regarding the role of statins in patients with heart failure (HF)/cardiomyopathy (CM), hypertension, atrial fibrillation (AF) and chronic kidney disease (CKD). As for patients with HF/CM inhibition of inflammation, reducing endothelial dysfunction might comprise part of the underlying mechanisms leading to the improvement of left ventricular function and exercise tolerance in these groups of patients. Therefore the candidates for statin therapy with HF/CM should be in New York Heart Association class II or III and should have normal or increased levels of lipids. We should avoid reducing lipids levels in these patients. At present, it is also difficult to unequivocally assess the impact of statins on blood pressure (BP). However, according to most available studies, the impact of statins on the decrease in BP is slight, but significant, especially among patients with hypertension. Moreover statins significantly reduce cardiovascular events in patients with hypertension. Although the results of trials concerning the use of statins in CKD patients are conflicting, it is suggested that the benefits of statin use outweigh the drawbacks in patients with early-stage CKD, when the benefits can be effectively predicted. However, available large randomized clinical trials suggest a lack of efficacy in patients on renal replacement therapy. We also needs further data on the role of statins on AF, however the existing studies suggest beneficial impact of statins in these patients.     

The effects of protein intake on blood pressure and cardiovascular disease

PURPOSE OF REVIEW: Investigators, especially those from western countries, have commonly assumed that there is either no association or a direct association of protein intake with elevated blood pressure and atherosclerosis. In contrast, recent observational studies and clinical trials have suggested that increased protein intake, particularly protein from plant sources, might actually reduce blood pressure and prevent cardiovascular disease. RECENT FINDINGS: In epidemiological studies, an increased intake of protein has been associated with lower blood pressure and an attenuated increase in blood pressure over time. Furthermore, such studies also suggest that the beneficial effects of increased protein intake result from an increased consumption of protein from plant rather than animal sources. In several predominantly small trials, an increased intake of soy protein lowered blood pressure. With respect to clinical outcomes, reports from large cohort studies suggest that increased protein intake is associated with a reduced risk of ischemic heart disease and perhaps intraparenchymal hemorrhage. In other reports, a higher protein intake is one characteristic of a dietary pattern associated with a reduced risk of ischemic heart disease. The mechanisms by which protein could exert its beneficial effects include an increased intake of biologically active amino acids, peptides, or highly correlated nutrients. SUMMARY: Recent evidence suggests that an increased intake of protein, particularly plant protein, may lower blood pressure and reduce the risk of cardiovascular disease. However, the data are not sufficiently compelling to advocate an increased consumption of protein.