The increased prevalence of obesity in children and its complications have led to a greater interest in studying baroreflex sensitivity (BRS) in children. This review of BRS in children and adolescents includes subtopics on: 1. Resting values of BRS and their reproducibility, 2. Genetics of BRS, 3. The role of a primarily low BRS and obesity in the development of hypertension, and 4. Association of diabetes mellitus, BRS, and obesity. The conclusions specific to this age follow from this review: 1. The mean heart rate (HR) influences the measurement of BRS. Since the mean HR decreases during adolescence, HR should be taken into account. 2. A genetic dependency of BRS was found. 3. Low BRS values may precede pathological blood
-pressure elevation in children with white-coat hypertension. We hypothesize that low BRS plays an active role in the emergence of hypertension in youth. A contribution of obesity to the development of
hypertension was also found. We hypothesize that both factors, a primarily low BRS and obesity, are partially independent risk factors for hypertension in youths. 4. In diabetics, a low BRS compared to healthy children can be associated with insulin resistance. A reversibility of the BRS values could be possible after weight loss.
Stress is considered a risk factor associated with the development of various civilization diseases including cardiovascular diseases, malignant tumors and mental disorders. Research investigating mechanisms involved in stress-induced hypertension have attracted much attention of physicians and researchers, however, there are still ambiguous results
concerning a causal relationship between stress and long-term
elevation of blood pressure (BP). Several studies have observed that mechanisms involved in the development of stress-induced hyperte
nsion include increased activity of sympathetic nervous system (SNS), glucocorticoid (GC) overload and altered endothelial functionincluding decreased nitric oxide (NO) bioavailability. Nitric oxide is well known neurotransmitter, neuromodulatorand vasodilator involved in regulation of
neuroendocrine mechanisms and cardiovascular responses to stressors. Thus NO plays a crucial role in the regulation of the stress systems and thereby in the BP regulation in stress. Elevated NO synthesis, especially in the initial phase of stress, may be considered a stress-limiting mechanism, facilitating the recovery from stress to the resting levels via attenuation of both GC release and SNS activity as well as by increased NO-dependent vasorelaxation. On the other hand, reduced levels of NO were observed in the later phases of stress and in subjects with genetic predisposition to hypertension, irrespectively, in which reduced NO bioavailability may account for disruption of NO-mediated BP regulatory mechanisms and accentuated SNS and GC effects. This review summarizes current knowledge on the role of stress in development of hypertension with a special focus on the interactions among NO and other biological systems
affecting blood pressure and vascular function.
The endothelium contributes to the maintenance of vasodilator
tone by releasing endothelium-derived relaxing factors, including
nitric oxide (NO). In hypertension, endothelial nitric oxide
synthase (eNOS) produces less NO and could be one of the
contributing factors to the increased peripheral vascular
resistance. Agonist-induced Ca2+ entry is essential for the
activation of eNOS. The transient receptor potential vanilloid
type 4 (TRPV4) channel, a Ca2+-permeant cation channel, is
expressed in the endothelial cells and involved in the regulation
of vascular tone. The present study aimed to investigate the role
of TRPV4 channel in endothelium-dependent NO-mediated
relaxation of the resistance artery in hypertensive rats. Using
a wire myograph, relaxation response to the TRPV4 activator,
4α-phorbol-12,13-didecanoate (4αPDD) was assessed in
mesenteric arteries obtained from Wistar-Kyoto (WKY) and
spontaneously hypertensive rats (SHRs). Compared to WKY, SHR
demonstrated a significantly attenuated 4αPDD-induced
endothelium-dependent NO-mediated relaxation. Immunohistochemical analysis revealed positive staining for TRPV4 in the
endothelium of mesenteric artery sections in both WKY and SHR.
Furthermore, TRPV4 mRNA and protein expressions in SHR were
significantly lower than their expression levels in WKY rats.
We conclude that 4αPDD-induced endothelium-dependent
NO-mediated vasorelaxation is reduced in SHR and downergulation of TRPV4 could be one of the contributing mechanisms.
Impressive advances in molecular genetic techniques allow to analyze the effects of natural selection on the development of human genome. For example, the trend towards blonde hair and blue eyes was documented. The approach to analyze possible effects of natural selection on the evolution of recent phenotypes with high risk of cardiovascular disease has not been described yet. A possible effect on the evolution of two main risk factors - hypercholesterolemia and hypertension - is presented. The close relationship of non-HDL cholesterol blood concentration to the proportion of pro-inflammatory macrophages in human visceral adipose tissue might be a result of long-lasting natural selection. Individuals with higher proportion of this phenotype might also display a higher ability to fight infection, which was very common in human setting from prehistory until Middle Ages. Successful battle against infections increased the probability to survive till reproductive age. Similar hypothesis was proposed to explain frequent hypertension in African Americans. A long-lasting selection for higher ability to conserve sodium during long-term adaptation to low sodium intake and hot weather was followed by a short-term (but very hard) natural selection of individuals during transatlantic slave transport. Only those with very high capability to retain sodium were able to survive. Natural selection of phenotypes with high plasma cholesterol concentration and/or high blood pressure is recently potentiated by high-fat high-sodium diet and overnutrition. This hypothesis is also supported by the advantage of familial hypercholesterolemia in the 19th century (at the time of high infection disease mortality) in contrast to the disadvantage of familial hypercholesterolemia during the actual period of high cardiovascular disease mortality., R. Poledne, J. Zicha., and Seznam literatury
The aim of our observation was to establish whether or not renal
sympathetic denervation (RSD) may help control blood pressure (BP) levels in patients with severe hypertension refractory to pharmacological therapy.
Out of a group of 12 patients, candidates for RSD, with uncontrolled hypertension and a systolic BP over 190 mm Hg on repeated measurements despite optimal medication, four patients were excluded for multiple renal
arteries and one for hyperaldosteronism. Seven patients had RSD using a Symplicity device (5M, 2F) with a mean age of 64.9 years. While all were followed up for a minimum of 6 months, follow-up duration in the majority of them was substantially longer (12-20 months). At six months post-RSD, six of the seven patients showed a decrease in systolic BP by at least 15 mm Hg
while receiving the same or fewer doses of antihypertensive agents. A similar response was seen in diastolic BP. The BP decrease was maintained throughout whole follow-up. In a small group of patients with severe hypertension, we demonstrated that renal sympathetic denervation is capable of reducing blood pressure even in patients with severe hypertension.
Cardiovascular studies have confirmed that hydrogen sulphide (H2S) is involved in various signaling pathways in both physiological and pathological conditions, including hypertension. In contrast to nitric oxide (NO), which has a clear vasorelaxant action, H2S has both vasorelaxing and vasoconstricting effects on the cardiovascular system. H2S is an important antihypertensive agent, and the reduced production of H2S and the
alterations in its functions are involved in the initiation of spontaneous
hypertension. Moreover, cross-talk between H2S and NO has been reported. NO-H2S interactions include reactions between the molecules themselves, and each has been shown to regulate the endogenous production of the other. In addition, NO and H2S can interact to form a nitrosothiol/s complex, which has original properties and represents a novel nitroso-sulphide signaling pathway. Furthermore, recent results have shown that the interaction between H2S and NO could be involved in the endothelium-regulated compensatory mechanisms that are observed in juvenile spontaneously hypertensive rats. The present review is devoted to role of H2S in vascular tone regulation. We primarily focus on the mechanisms of H2S-NO interactions and on the role of H2S in blood pressure regulation in normotensive and spontaneously hypertensive rats.
The peroxisome proliferator-activated receptors (PPAR) belong to the nuclear superfamily of ligand-activated transcription factors. PPARγ acts as a nutrient sensor that regulates several homeostatic functions. Its disruption can lead to vascular pathologies, disorders of fatty acid/lipid metabolism and insulin resistance. PPARγ can modulate several signaling pathways connected with blood pressure regulation. Firstly, it affects the insulin signaling pathway and endothelial dysfunction by modulation of expression and/or phosphorylation of signaling molecules through the PI3K/Akt/eNOS or MAPK/ET-1 pathways. Secondly, it can modulate gene expression of the renin- angiotensin system – cascade proteins, which potentially slow down the progression of atherosclerosis and hypertension.
Thirdly, it can modulate oxidative stress response either directly through PPAR or indirectly through Nrf2 activation. In this context, activation and functioning of PPARγ is very important in the regulation of several disorders such as diabetes mellitus, hypertens
ion and/or metabolic syndrome.