Vascular smooth muscle cells (VSMC) display considerable phenotype plasticity which can be studied in vivo on vascular remodeling which occurs during acute or chronic vascular injury. In differentiated cells, which represent contractile phenotype, there are characteristic rapid transient changes of intracellular Ca2+ concentration ([Ca2+]i), while the resting cytosolic [Ca2+]i concentration is low. It is mainly caused by two components of the Ca2+ signaling pathways: Ca2+ entry via L-type voltagedependent Ca2+ channels and dynamic involvement of intracellular stores. Proliferative VSMC phenotype is characterized by long-lasting [Ca2+]i oscillations accompanied by sustained elevation of basal [Ca2+]i. During the switch from contractile to proliferative phenotype there is a general transition from voltagedependent Ca2+ entry to voltage-independent Ca2+ entry into the cell. These changes are due to the altered gene expression which is dependent on specific transcription factors activated by various stimuli. It is an open question whether abnormal VSMC phenotype reported in rats with genetic hypertension (such as spontaneously hypertensive rats) might be partially caused by a shift from contractile to proliferative VSMC phenotype., E. Misárková, M. Behuliak, M. Bencze, J. Zicha., and Obsahuje bibliografii
Treatment with pertussis toxin (PTX) which eliminates the activity of Gi proteins effectively reduces blood pressure (BP) and vascular resistance in spontaneously hypertensive rats (SHR). In this study we have compared the functional characteristics of isolated arteries from SHR with and without PTX-treatment (10 μg/kg i.v., 48 h before the experiment). Rings of thoracic aorta, superior mesenteric artery and main pulmonary artery were studied under isometric conditions to measure the reactivity of these vessels to receptor agonists and to transmural electrical stimuli. We have found that the treatment of SHR with PTX had no effect on endothelium-dependent relaxation of thoracic aorta induced by acetylcholine. In PTX-treated SHR, the maximum contraction of mesenteric artery to exogenous noradrenaline was reduced and the dose-response curve to cumulative concentration of noradrenaline was shifted to the right. Similarly, a reduction in the magnitude of neurogenic contractions elicited by electrical stimulation of perivascular nerves was observed in the mesenteric artery from PTX-treated SHR. PTX treatment of SHR also abolished the potentiating effect of angiotensin II on neurogenic contractions of the main pulmonary artery. These results indicate that PTX treatment markedly diminishes the effectiveness of adrenergic stimuli in vasculature of SHR. This could importantly affect BP regulation in genetic hypertension., A. Zemančíková, J. Török, J. Zicha, J. Kuneš., and Obsahuje bibliografii a bibliografické odkazy
High blood pressure (BP) of L-NAME hypertensive rats is maintained not only by the absence of nitric oxide (NO)-dependent vasodilatation but also by the enhancement of both sympathetic and angiotensin II-dependent vasoconstriction. The aim of the present study was to evaluate the role of inhibitory G (Gi) proteins, which are involv ed in tonic sympathetic vasoconstriction, in the pathogenesis of NO-deficient hypertension. We therefore studied BP response to chronic L-NAME administration (60 mg/kg/day for 4 weeks) in rats in which the in vivo inactivation of Gi proteins was induced by injection of pertussis toxin (PTX, 10 μg/kg i.v.). The impairment of sympathetic vasoconstriction due to PTX-induced Gi protein inactivation prevents the full development of NO-deficient hypertension because BP of PTX-treated rats subjected to chronic L-NAME administration did not reach hypertensive values. Nevertheless, chronic NO synthase inhibition per se is capable to increase moderately BP even in PTX-treated rats. Our data suggest that the sympathetic vasoconstriction is essential for the development of established NO-deficient hypertension., J. Zicha ... [et al.]., and Obsahuje seznam literatury
Spontaneously hypertensive rats (SHR) are characterized by enhanced nifedipine-sensitive component of sympathetic vasoconstriction. Our study tried to elucidate the mechanisms responsible for long-term reduction of blood pressure (BP) in SHR subjected to early transient captopril treatment. Adult untreated SHR aged 30-34 weeks were compared with animals subjected to chronic captopril treatment for 6 weeks either in youth (between 4 and 10 weeks of age) or in adulthood (between 24 and 30 weeks of age). Antihypertensive effects of captopril were more pronounced in young than adult SHR. This was due to greater attenuation of sympathetic and nifedipine-sensitive BP components and prevention of residual BP rise in young captopril-treated SHR in which the reductions of nifedipine-sensitive BP component and residual BP persisted for 20 weeks after captopril withdrawal. The magnitude of nifedipine-sensitive component of sympathetic vasoconstriction is decisive for BP maintenance not only in untreated SHR but also in SHR during active captopril treatment by or after its withdrawal., J. Zicha, Z. Dobešová,J. Kuneš., and Obsahuje bibliografii a bibliografické odkazy
The development of neurogenic pulmonary edema (NPE) can be elicited by an immediate epidural balloon compression of the thoracic spinal cord. To evaluate whether a slower balloon inflation could prevent NPE development, we examined the extent of NPE in animals lesioned with a rapid (5 μl - 5 μl - 5 μl) or slow rate (3 μl - 2 μl - 2 μl - 2 μl - 2 μl - 2 μl - 2 μl) of balloon inflation. These groups were compared with the NPE model (immediate inflation to 15 μl) and with healthy controls. Slow balloon inflation prevented NPE development, whereas the pulmonary index and histology revealed a massive pulmonary edema in the group with a rapid rate of balloon inflation. Pulmonary edema was preceded by a considerable decrease in heart rate during the inflation procedure. Moreover, rapid inflation of balloon in spinal channel to either 5 μl or 10 μl did not cause NPE. Thus, a slow rate of balloon inflation in the thoracic epidural space prevents the development of neurogenic pulmonary edema, most likely due to the better adaptation of the organism to acute circulatory changes (rapid elevation of systemic blood pressure accompanied by profound heart rate reduction) during the longer balloon inflation period. It should be noted that spinal cord transection at the same level did not cause neurogenic pulmonary edema., J. Šedý ... [et al.]., and Obsahuje seznam literatury
Enhanced production of superoxide radicals by nicotinamideadenine dinucleotide phosphate (NADPH) oxidase in the brain and/or kidney of salt hypertensive Dahl rats has been proposed to participate in the pathogenesis of this form of experimental hypertension. Most information was obtained in young Dahl saltsensitive (DS) rats subjected to high salt intake prior to sexual maturation. Therefore, the aim of our study was to investigate whether salt hypertension induced in adult DS rats is also accompanied with a more pronounced oxidative stress in the brain or kidney as compared to Dahl salt-resistant (DR) controls. NADPH oxidase activity as well as the content of thiobarbituric acid-reactive substances (TBARS) and conjugated dienes (oxidative index), which indicate a degree of lipid peroxidation, were evaluated in two brain regions (containing either hypothalamic paraventricular nucleus or rostral ventrolateral medulla) as well as in renal medulla and cortex. High salt intake induced hypertension in DS rats but did not modify blood pressure in DR rats. DS and DR rats did not differ in NADPH oxidase-dependent production of ROS, TBARS content or oxidative index in either part of the brain. In addition, high-salt diet did not change significantly any of these brain parameters. In contrast, the enhanced NADPH oxidase-mediated ROS production (without significant signs of increased lipid peroxidation) was detected in the renal medulla of salt hypertensive DS rats. Our findings suggest that there are no signs of enhanced oxidative stress in the brain of adult Dahl rats with salt hypertension induced in adulthood., M. Vokurková, H. Rauchová, L. Řezáčová, I. Vaněčková, J. Zicha., and Obsahuje bibliografii
We investigated the effect of pertussis toxin (PTX) on hypotensive response induced by acetylcholine (ACh) and bradykinin (BK) and on noradrenaline (NA)-induced pressor response in spontaneously hypertensive rats (SHR). Fifteen-week-old Wistar rats and age-matched SHR were used. Half of SHR received PTX (10 μg/kg/i.v.) and the experiments were performed 48 h later. After the anesthesia the right carotid artery was cannulated in order to record blood pressure (BP). The hypotensive response to ACh was enhanced in SHR compared to Wistar rats. After pretreatment of SHR with PTX the hypotensive response to ACh was reduced compared to untreated SHR and it was also diminished in comparison to Wistar rats. Similarly, the hypotensive response to BK was also decreased after PTX pretreatment. The pressor response to NA was increased in SHR compared to Wistar rats. NA-induced pressor response was considerably decreased after PTX pretreatment compared to untreated SHR. In conclusion, the enhancement of hypotensive and pressor responses in SHR was abolished after PTX pretreatment. Our results suggested that the activation of PTX-sensitive inhibitory Gi proteins is involved in the regulation of integrated vasoactive responses in SHR and PTX pretreatment could be effectively used for modification of BP regulation in this type of experimental hypertension., S. Čačányiová, F. Kristek, J. Kuneš, J. Zicha., 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