ncreased systemic vascular resistance is responsible for blood pressure (BP) elevation in most forms of human or experimental hypertension. The enhanced contractility of structurally remodeled resistance arterioles is mediated by enhanced calcium entry (through L type voltagedependent calcium channels - L-VDCC) and/or augmented calcium sensitization (mediated by RhoA/Rho kinase pathway). It is rather difficult to evaluate separately the role of these two pathways in BP control because BP response to the blockade of either pathway is always dependent on the concomitant activity of the complementary pathway. Moreover, vasoconstrictor systems enhance the activity of both pathways, while vasodilators attenuate them. The basal fasudil-sensitive calcium sensitization determined in rats deprived of endogenous renin-angiotensi n system (RAS) and sympathetic nervous system (SNS) in wh ich calcium entry was dose- dependently increased by L-VDCC opener BAY K8644, is smaller in spontaneously hypertensive rats (SHR) than in normotensive Wistar-Kyoto (WKY) rats. In co ntrast, if endogenous RAS and SNS were present in intact rats, fasudil caused a greater BP fall in SHR than WKY rats. Our in vivo experiments indicated that the endogenous pressor systems (RAS and SNS) augment calcium sensitization mediated by RhoA/Rho kinase pathway, whereas the endogenous vasodilator systems (such as nitric oxide) attenuate this pathway. However, the modulation of calcium entry and calcium sensitization by nitric oxide is strain-dependent because NO deficiency significan tly augments low calcium entry in WKY and low calcium sensitization in SHR. Further in vivo and in vitro experiments should clarify the interrelationships between endogenous vasoactive systems an d the contribution of calcium entry and/or calcium sensitization to BP maintenance in various forms of experimental hypertension., J. Zicha ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Essential hypertension is a major risk factor for several cardiovascular diseases. It is a complex trait resulting from the interactions of multiple genetic and environmental factors. Moreover, not only genetic but also epigenetic inheritance plays a significant role. One can speculate that hypertension develops as a consequence of “errors” in well-coordinated regulatory systems of blood pressure. Errors in the cascade of molecular, biochemical and genetic processes, which regulate blood pressure, have finally enough potential to result in hypertension. Numerous environmental factors surrounding the organism during its development should influence the expression of genetic information. However, despite the considerable research effort, it is still difficult to identify all genes and/or other genetic determinants leading to essential hypertension and other cardiovascular diseases. This is mainly because these diseases usually become a medical problem in adulthood, although their roots might be traced back to earlier stages of ontogeny. The link between distinct developmental periods (e.g. birth and adulthood) should involve changes in gene expression involving epigenetic phenomena. The purpose of the present paper is to bring a piece of light on gene-environmental interactions potentially implicated in the pathogenesis of hypertension., J. Kuneš, J. Zicha., and Obsahuje seznam literatury
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