Endothelial dysfunction may be considered as the interstage between risk factors and cardiovascular pathology. An imbalance between the production of vasorelaxing and vasoconstricting factors plays a decisive role in the development of hypertension, atherosclerosis and target organ damage. Except vasorelaxing and antiproliferative properties per se, nitric oxide participates in antagonizing vasoconstrictive and growth promoting effects of angiotensin II, endothelins and reactive oxygen species. Angiotensin II is a potent activator of NAD(P)H oxidase contributing to the production of reactive oxygen species. Numerous signaling pathways activated in response to angiotensin II and endothelin-1 are mediated through the increased level of oxidative stress, which seems to be in casual relation to a number of cardiovascular disturbances including hypertension. With respect to the oxidative stress, the NO molecule seems to be of ambivalent nature. On the one hand, NO is able to reduce generation of reactive oxygen species by inhibiting association of NAD(P)H oxidase subunits. On the other hand, when excessively produced, NO reacts with superoxides resulting in the formation of peroxynitrite, which is a free radical deteriorating endothelial function. The balance between vasorelaxing and vasoconstricting substances appears to be the principal issue for the physiological functioning of the vascular bed., O. Pecháňová, F. Šimko., and Obsahuje bibliografii
Clinical and experimental studies have repeatedly indicated that overloaded hearts have a higher vulnerability to ischemia/reperfusion injury. The aim of the present study was to answer the question whether the degree of tolerance to oxygen deprivation in hearts of spontaneously hypertensive rats (SHR) may be sex-dependent. For this purpose, adult SHR and their normotensive control Wistar Kyoto (WKY) rats were used. The isolated hearts were perfused according to Langendorff at constant pressure (proportionally adjusted to the blood pressure in vivo). Recovery of contractile parameters (left ventricular systolic, diastolic and developed pressure as well as the peak rate of developed pressure) was measured during reperfusion after 20 min of global no-flow ischemia in 5 min intervals. Mean arterial blood pressure was measured by direct puncture of carotid artery under light ether anesthesia in a separate group of animals. The degree of hypertension was comparable in both sexes of SHR. The recovery of contractile functions in SHR males and females was significantly lower than in WKY rats during the whole investigated period. There was no sex difference in the recovery of WKY animals; on the other hand, the recovery was significantly better in SHR females than in SHR males. It may be concluded that the hearts of female SHR are more resistant to ischemia/reperfusion injury as compared with male SHR. This fact could have important clinical implications for the treatment of cardiovascular disease in women., J. Bešík, O. Szárszoi, J. Kuneš, I. Netuka, J. Malý, F. Kolář, J. Pirk, B. Ošťádal., and Obsahuje bibliografii a bibliografické odkazy
Cardiovascular diseases are the most common cause of mortality and morbidity in most populations. As the traditional modifiable risk factors (smoking, hypertension, dyslipidemia, diabetes mellitus, and obesity) were defined decades ago, we decided to analyze recent data in patients who survived acute coronary syndrome (ACS). The Czech part of the study included data from 999 males, and compared them with the post-MONICA study (1,259 males, representing general population). The Lithuanian study included 479 male patients and 456 age-matched controls. The Kazakhstan part included 232 patients and 413 controls. In two countries, the most robust ACS risk factor was smoking (OR 3.85 in the Czech study and 5.76 in the Lithuanian study), followed by diabetes (OR 2.26 and 2.07) and hypertension (moderate risk elevation with OR 1.43 and 1.49). These factors did not influence the ACS risk in Kazakhstan. BMI had no significant effect on ACS and plasma cholesterol was surprisingly significantly lower (P<0.001) in patients than in controls in all countries (4.80 ±1.11 vs. 5.76 ±1.06 mmol /l in Czechs; 5.32 ±1.32 vs. 5.71 ±1.08 mmol /l in Lithuanians; 4.88 ±1.05 vs. 5.38±1.13 mmol /l in Kazakhs/Russians). Results from our study indicate substantial heterogeneity regarding major CVD risk factors in different populations with the exception of plasma total cholesterol which was inversely associated with ACS risk in all involved groups. These data reflect ethnical and geographical differences as well as changing pattern of cardiovascular risk profiles., J. A. Hubacek, V. Stanek, M. Gebauerova, V. Adamkova, V. Lesauskaite, D. Zaliaduonyte-Peksiene, A. Tamosiunas, A. Supiyev, A. Kossumov, A. Zhumadilova, J. Pitha., and Obsahuje bibliografii
Genetic predisposition and social stress may represent important risk factors in etiology of hypertension associated with endothelial dysfunction. Perturbations of endothelial structural integrity are also critical for the pathogenesis of vascular diseases. We examined effect of chronic social stress on structure of aortic endothelium in bord erline hypertensive (BHR) and normotensive Wistar rats. Male BHR – offspring of Wistar mothers and SHR fathers and age-matched W were exposed to 6-week crowding stress (5 rats/cage, 200 cm2/rat). Aortic tissue was processed for electron microscopy and NO synthase activity measurement. Crowding stress significantly increased blood pressure in BHR compared to basal values (140±3 mm Hg vs. 130±3 mm Hg, p<0.05) and reduced enzyme activity by 37 % (p<0.01) in the aorta of BHR. Local slight structural alterations of endothelium were found in non-stressed BHR (p<0.001) when compared with Wistar rats. Chronic stress caused marked (p<0.005) subcellular injury of endothelial cells in aorta of BHR characterized by mitochondrial damage, presence of vacuoles, increased number of lysosomes, Weibel-Palade bodies, changes of intercellular connections and local disruption of endothelium, while only slight changes were seen in Wistar rats. Results suggest increased sensitivity of aortic endothelium of BHR to chronic crowding that may contribute to acceleration of arterial dysfunction., Ľ. Okruhlicová, K. Dlugošová, M. Mitašíková, I. Bernátová., and Obsahuje bibliografii a bibliografické odkazy
Pathophysiological mechanisms underlying the development of renal dysfunction and progression of congestive heart failure (CHF) remain poorly understood. Recent studies have revealed striking differences in the rol e of epoxyeicosatrienoic acids (EETs), active products of cytochrome P-450-dependent epoxygenase pathway of arachidonic acid, in the progression of aorto-caval fistula (ACF)-induced CHF between hypertensive Ren-2 renin transgenic rats (TGR) and transgene-negative normotensive Hannover Sprague-Dawley (HanSD) controls. Both ACF TGR and ACF HanSD strains exhibited marked intrarenal EETs deficiency and impairment of renal function, and in both strains chronic pharmacologic inhibition of s oluble epoxide hydrola se (sEH) (which normally degrades EETs) normalized EETs levels. However, the treatment improved the survival rate and attenuated renal function impairment in ACF TGR only. Here we aimed to establish if the reported improved renal function and attenuation o f progression of CHF in ACF TGR observed after sEH blockade depends on increased vasodilatory responsiveness of renal resistance arteries to EETs. Therefore, we examined the responses of interlobar arteries from kidneys of ACF TGR and ACF HanSD rats to EET-A, a new stable 14,15-EET analog. We found that the arteries from ACF HanSD kidneys rats exhibited greater vasodilator responses when compared to the ACF TGR arteries. Hence, reduced renal vasodilatory responsiveness cannot be responsible for the lack of beneficial effects of chronic sEH inhibition on the development of renal dysfunction and progression of CHF in ACF HanSD rats., A. Sporková, Z. Husková, P. Škaroupková, N. Rami Reddy, J. R. Falck, J. Sadowski, L. Červenka., and Obsahuje bibliografii