We studied the relationship between blood pressure (BP), body mass index (BMI, kg/m2) and baroreflex sensitivity (BRS, ms/mmHg) in adolescents. We examined 34 subjects aged 16.2±2.4 years who had repeatedly high causal BP (H) and 52 controls (C) aged 16.4±2.2 years. Forty-four C and 22 H were of normal weight (BMI between 19-23.9), and 8 C and 12 H were overweight (BMI between 24-30). Systolic BP was recorded beat-to-beat for 5 min (Finapres, controlled breathing 0.33 Hz). BRS was determined by the cross-spectral method. The predicting power of BMI and BRS for hypertension was evaluated by sensitivity, specificity, and receiver operating curve (ROC - plot of sensitivity versus specificity). H compared with C had lower BRS (p<0.01) and higher BMI (p<0.05). Multiple logistic regression analysis (p<0.001) revealed that a decreased BRS (p<0.05) and an increased BMI (p<0.01) were independently associated with an increased risk of hypertension. No correlation between BMI and BRS was found either in H or in C. Following optimal critical values by ROC, the sensitivity, specificity and area under ROC were determined for: BMI - 22.2 kg/m2, 61.8 %, 69.2 %, 66.0 %; BRS - 7.1 ms/mmHg, 67.7 %, 69.2 %, 70.0 %; BMI and BRS - 0.439 a.u., 73.5 %, 82.7 %, and 77.3 %. Decreased BRS and overweight were found to be independent risk factors for hypertension., K. Krontorádová, N. Honzíková, B. Fišer, Z. Nováková, E. Závodná, H. Hrstková, P. Honzík., and Obsahuje bibliografii a bibliografické odkazy
This review concerns the role of nitric oxide (NO) in the pathogenesis of different models of experimental hypertension (NO-deficient, genetic, salt-dependent), which are characterized by a wide range of etiology. Although the contribution of NO may vary between different models of hypertension, a unifying characteristic of these models is the presence of oxidative stress that participates in the maintenance of elevated arterial pressure and seems to be a common denominator underlying endothelial dysfunction in various forms of experimental hypertension. Besides the imbalance between the endothelial production of vasorelaxing and vasoconstricting compounds as well as the relative insufficiency of vasodilator systems to compensate augmented vasoconstrictor systems, there were found numerous structural and functional abnormalities in blood vessels and heart of hypertensive animals. The administration of antihypertensive drugs, antioxidants and NO donors is capable to attenuate blood pressure elevation and to improve morphological and functional changes of cardiovascular system in some but not all hypertensive models. The failure to correct spontaneous hypertension by NO donor administration reflects the fact that sympathetic overactivity plays a key role in this form of hypertension, while NO production in spontaneously hypertensive rats might be enhanced to compensate increased blood pressure. A special attention should be paid to the modulation of sympathetic nervous activity in central and peripheral nervous system. These results extend our knowledge on the control of the balance between NO and reactive oxygen species production and are likely to be a basis for the development of new approaches to the therapy of diseases associated with NO deficiency., J. Török., and Obsahuje bibliografii a bibliografické odkazy
Solid organ transplantation is an established treatment modality in patients with end-stage organ damage in cases where other therapeutic options fail. The long-term outcomes of solid organ transplant recipients have improved considerably since the introduction of the first calcineurin inhibitor (CNI) - cyclosporine. In 1984, the potent immunosuppressive properties of another CNI, tacrolimus, were discovered. The immunosuppressive effects of CNIs result from the inhibition of interleukin-2 synthesis and reduced proliferation of T cells due to calcineurin blockade. The considerable side effects that are associated with CNIs therapy include arterial hypertension and nephrotoxicity. The focus of this article was to review the available literature on the pathophysiological mechanisms of CNIs that induce chronic nephrotoxicity and arterial hypertension. CNIs lead to activation of the major vasoconstriction systems, such as the reninangiotensin and endothelin systems, and increase sympathetic nerve activity. On the other hand, CNIs are known to inhibit NO synthesis and NO-mediated vasodilation and to increase free radical formation. Altogether, these processes cause endothelial dysfunction and contribute to the impairment of organ function. A better insight into the mechanisms underlying CNI nephrotoxicity could assist in developing more targeted therapies of arterial hypertension or preventing CNI nephrotoxicity in organ transplant recipients, including heart transplantation., L. Hošková, I. Málek, L. Kopkan, J. Kautzner., and Obsahuje bibliografii
Gap junction connexin channels are important determinants of myocardial conduction and synchronization that is crucial for coordinated heart function. One of the main risk factors for cardiovascular events that results in heart attack, congestive heart failure, stroke as well as sudden arrhythmic death is hypertension. Mislocalization and/or dysfunction of specific connexin-43 channels due to hypertension-induced myocardial remodeling have been implicated in the occurrence of lifethreatening arrhythmias and heart failure in both, humans as well as experimental animals. Recent studies suggest that downregulation of myocardial connexin-43, its abnormal distribution and/or phosphorylation might be implicated in this process. On the other hand, treatment of hypertensive animals with cardioprotective drugs (e.g. statins) or supplementation with non-pharmacological compounds, such as melatonin, omega-3 fatty acids and red palm oil protects from lethal arrhythmias. The antiarrhythmic effects are attributed to the attenuation of myocardial connexin-43 abnormalities associated with preservation of myocardial architecture and improvement of cardiac conduction. Findings uncover novel mechanisms of cardioprotective (antihypertensive and antiarrhythmic) effects of compounds that are used in clinical settings. Well-designed trials are needed to explore the antiarrhythmic potential of these compounds in patients suffering from hypertension., T. Egan Benova, B. Szeiffova Bacova, C. Viczenczova, E. Diez, M. Barancik, N. Tribulova., and Obsahuje bibliografii
The spontaneously hypertensive rat (SHR) is the most widely used animal model of essential hypertension an d accompanying metabolic disturbances. Recent advances in sequencing of genomes of BN- Lx and SHR progenitors of the BXH/HXB recombinant inbred (RI) strains as well as ac cumulation of multiple data sets of intermediary phenotypes in the RI strains, including mRNA and microRNA abundance, quantitative metabolomics, proteomics, methylomics or histone modifications, will make it possible to systematically search for genetic variants involved in regulation of gene ex pression and in the etiology of complex pathophysiological traits. New advances in manipulation of the rat genome, including e fficient transgenesis and gene targeting, will enable in vivo functional analys es of selected candidate genes to identify QTL at the molecular level or to provide insight into mechanisms whereby targeted genes affect pathophysiological traits in the SHR., M. Pravenec ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
The objective of the present study was to compare systemic and regional haemodynamics in a large series of spontaneously hypertensive rats (SHR, n = 32) with normotensive Wistar-Kyoto rats (WKY, n = 26) at the age of 12—16 weeks. All rats were anaesthetized with thiobutabarbital and the radioactively labelled microsphere method was used to evaluate regional blood flow with special emphasis on different cerebral areas. The high blood pressure in the SHR was mainly due to elevated total peripheral resistance, which was 90 % higher in the SHR compared to the WKY. Furthermore, heart rate was 25 % (p< 0.001) higher, but the cardiac index was lower by 20 % (p<0.01) in the SHR. Blood flow was significantly lower and vascular resistance higher in several organs such as the kidneys, other visceral organs, skeletal muscle and skin of the SHR compared to the WKY. On the contrary, blood How in the myocardium was augmented by 40 % (p<0.01) in the SHR. Blood flow was 20-50 % higher in the cerebral cortex, thalamus and caudatus (p<0.05-0.001), but attenuated in the hypophysis of the SHR. In the pons, medulla and cerebellum, blood flow was similar in the two strains. In this large microsphere study, the basal cardiac index was lower in the SHR already at this relatively early stage of established hypertension. Despite this, increased blood flow in the above mentioned cerebral regions was found in the SHR compared to the WKY.
The present study was focused on regulatory role of nitric oxide on functional properties of the cardiac Na, K-ATPase in three various animal models of hypertension: spontaneously hypertensive male rats (SHR) with increased activity of nitric oxide synthase (NOS) by 60 % (Sh1), SHR with decreased activity of NOS by 40 % (Sh2) and rats with hypertension induced by L-NAME (40 mg/kg/day) with depressed activity of NOS by 72 % (LN). Studying the utilization of energy substrate we observed higher Na, K-ATPase activity in the whole concentration range of ATP in Sh1 and decreased activity in Sh2 and LN. Evaluation of kinetic parameters revealed an increase of Vmax value by 37 % in Sh1 and decrease by 30 % in Sh2 and 17 % in LN. The KM value remained unchanged in Sh2 and LN, but was lower by 38 % in Sh1 indicating increased affinity of the ATP binding site, as compared to controls. During the activation with Na+ we observed increased Vmax by 64 % and increased KNa by 106 % in Sh1. In Sh2 we found decreased Vmax by 40 % and increased KNa by 38 %. In LN, the enzyme showed unchanged Vmax with increased KNa by 50 %. The above data indicate a positive role of increased activity of NOS in improved utilization of ATP as well as enhanced binding of Na+ by the cardiac Na, K-ATPase., J. Vlkovičová, V. Javorková, L. Mézešová, O. Pecháňová, N. Vrbjar., and Obsahuje bibliografii a bibliografické odkazy
Arterial wall stiffness is considered an independent cardiovascular risk factor. Aim of this study was to evaluate relationship between clinical, 24-hour, average day-time and night-time blood pressure (BP) and measures of arterial stiffness assessed by pulse wave velocity (PWV) (using SphygmoCor applanation tonometer) in essential hypertension (severe-resistant (RH, n=29) and moderate hypertension (EH, n=35)) and in normotensive control subjects (n-29) (NCS) matched by age. After multiple regression analysis, PWV remains significantly correlated mainly with night-time pulse pressure and to a lesser extent with age. PWV was significantly higher in RH compared to moderate EH and NCS., J. Rosa, B. Štrauch, O. Petrák, T. Pikus, R. Holaj, T. Zelinka, D. Wichterle, J. Widimský Jr., and Obsahuje bibliografii a bibliografické odkazy
Renin-angiotensin system (RAS) plays a key role in the regulation of renal function, volume of extracellular fluid and blood pressure. The activation of RAS also induces oxidative stress, particularly superoxide anion (O2-) formation. Although the involvement of O2- production in the pathology of many diseases is known for long, recent studies also strongly suggest its physiological regulatory function of many organs including the kidney. However, a marked accumulation of O2- in the kidney alters normal regulation of renal function and thus may contribute to the development of salt-sensitivity and hypertension. In the kidney, O2- acts as vasoconstrictor and enhances tubular sodium reabsoption. Nitric oxide (NO), another important radical that exhibits opposite effects than O2-, is also involved in the regulation of kidney function. O2- rapidly interacts with NO and thus, when O2- production increases, it diminishes the bioavailability of NO leading to the impairment of organ function. As the activation of RAS, particularly the enhanced production of angiotensin II, can induce both O2- and NO generation, it has been suggested that physiological interactions of RAS, NO and O2- provide a coordinated regulation of kidney function. The imbalance of these interactions is critically linked to the pathophysiology of salt-sensitivity and hypertension., L. Kopkan, L. Červenka., and Obsahuje seznam literatury