Maintenance of norepinephrine (NE)-induced contraction is dependent on Ca2+ influx through L-type voltage-dependent Ca2+ channels (VDCC), which is opposed by nitric oxide. Adrenergic receptors are coupled with different G proteins, including inhibitory G proteins (Gi) that can be inactivated by pertussis toxin (PTX). Our study was aimed to investigate the effects of endothelium removal, PTX pretreatment and acute VDCC blockade by nifedipine on the contractions of femoral arteries stimulated by norepinephrine. We used 12-week-old male WKY, half of the rats being injected with PTX (10 μg/kg i.v., 48 h before the experiment), which considerably reduced their blood pressure (BP). Contractions of isolated arteries were measured using Mulvany-Halpern myograph. NE dose-response curves determined in femoral arteries from PTX-treated WKY rats were shifted to the right compared to those from control WKY. On the contrary, removal of endothelium augmented NE dose-response curves shifting them to the left. Acute VDCC blockade by nifedipine (10-7 M) abolished all differences in NE dose-response curves which were dependent on the presence of either intact endothelium or functional Gi proteins because all NE dose-response curves were identical to the curve seen in vessels with intact endothelium from PTX-treated animals. We can conclude that BP reduction after PTX injection is accompanied by the attenuation of NE-induced contraction of femoral arteries irrespective of endothelium presence. Moreover, our data indicate that both vasodilator action of endothelium and Gi-dependent vasoconstrictor effect of norepinephrine operate via the control of Ca2+ influx through VDCC., S. Líšková, J. Kuneš, J. Zicha., and Obsahuje bibliografii a bibliografické odkazy
The objective of the current study was to search for genetic determinants associated with antihypertensive effects of angiotensin-converting enzyme (ACE) inhibitor captopril. Linkage and correlation analyses of captopril-induced effects on blood pressure (BP) with renal transc riptome were performed in the BXH/HXB recombinant inbred (RI) strains derived from spontaneously hypertensive rat (SHR) and Brown Norway (BN-Lx) progenitors. Variability of blood pressure lowering effects of captopril among RI strains was continuous suggesting a polygenic mode of inheritance. Linkage analysis of captopril- induced BP effects revealed a significant quantitative trait locus (QTL) on chromosome 15. This QTL colocalized with cis regulated expression QTL (eQTL) for the Ednrb (endothelin receptor type B) gene in the kidney (SHR allele was associated with increased renal expression) and renal expression of Ednrb correlated with captopril-induced BP effects. These results suggest that blood pressure lowering effects of ACE inhibitor captopril may be modulated by the variants at the Ednrb locus., J. Zicha ... [et al.]., 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
Factors modulating cardiac susceptibility to ischemia-reperfusion (I/R) are permannetly attracting the attention of experimental cardiology research. We investigated, whether continuous 24 h/day light exposure of rats can modify cardiac response to I/R, NO-synthase (NOS) activity and the level of oxidative load represented by conjugated dienes (CD) concentration. Two groups of male adult Wistar rats were studied: controls exposed to normal light/dark cycle (12 h/day light, 12 h/day dark) and rats exposed to continuous light for 4 weeks. Perfused isolated hearts (Langendorff technique) were exposed to 25 min global ischemia and subsequent 30 min reperfusion. The recovery of functional parameters (coronary flow, left ventricular developed pressure, contractility and relaxation index) during reperfusion as well as the incidence, severity and duration of arrhythmias during first 10 min of reperfusion were determined. The hearts from rats exposed to continuous light showed more rapid recovery of functional parameters but higher incidence, duration and severity of reperfusion arrhythmias compared to controls. In the left ventricle, the NOS activity was attenuated, but the CD concentration was not significantly changed. We conclude that the exposure of rats to continuous light modified cardiac response to I/R. This effect could be at least partially mediated by attenuated NO production., R. Važan, P. Janega, S. Hojná, J. Zicha, F. Šimko, O. Pecháňová, J. Styk, L'. Paulis., 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
Catecholaminergic system plays an important role in hypertension development. The available results on mRNA expression of catecholaminergic system genes in spontaneously hypertensive rats (SHR) are often contradictory. One of the possible causes might be the use of various reference genes as internal controls. In the present study, we searched for suitable reference genes in adrenal medulla or sympathetic ganglia of SHR and Wistar-Kyoto (WKY) rats, which would enable reliable comparison of mRNA expression between these two strains. The mRNA expression was measured by quantitative real-time PCR in adrenal medulla and superior cervical ganglia of 4-week-old or 24-week-old SHR and WKY rats. We evaluated 12 reference genes by three software tools (Normfinder, BestKeeper, geNorm) and compared them for the standardization of mRNA expression. Combination of reference genes Hprt1 and Ywhaz in adrenal medulla and Gapdh and 18S in sympathetic ganglia were chosen as the best ones. 18S was found as applicable reference gene in both tissues. We found many alterations in expression of catecholaminergic system genes in adrenal medulla and sympathetic ganglia of SHR. The usage of the most or the least stable reference gene as internal control changed results moderately in sympathetic ganglia but seriously in adrenal medulla. For example, tyrosine hydroxylase (Th) gene was underexpressed in adrenal medulla of adult SHR using the appropriate reference gene but unchanged after the standardization to the least stable reference gene. Our results indicate the importance of appropriate internal control. The suitability of reference genes should be checked again in the case of change in experimental conditions., A. Vavřínová, M. Behuliak, J. Zicha., and Obsahuje bibliografii