High blood pressure (BP) of spontaneously hypertensive rats (SHR) is maintained by enhanced activity of sympathetic nervous system (SNS), whereas that of Ren-2 transgenic rats (Ren-2 TGR) by increased activity of renin-angiotensin system (RAS). However, both types of hypertension are effectively attenuated by chronic blockade of L-type voltage-dependent calcium channel (L-VDCC). The aim of our study was to evaluate whether the magnitude of BP response elicited by acute nifedipine administration is proportional to the alterations of particular vasoactive systems (SNS, RAS, NO) known to modulate L-VDCC activity. We therefore studied thes e relationships not only in SHR, in which mean arterial pressure was modified in a wide range of 100-210 mm Hg by chronic antihypertensive treatment (captopril or hydralazine) or its withdrawal, but also in rats with augmented RAS activity such as homozygous Ren-2 TGR, pertussis toxin- treated SHR or L-NAME-treated SHR. In all studied groups the magnitude of BP response to nifedipine was proportional to actual BP level and it closely correlated with BP changes induced by acute combined blockade of RAS and SNS. BP response to nifedipine is also closely related to the degree of relative NO deficiency. This was true for both SNS- and RAS-dependent forms of genetic hypertension, suggesting common mechanisms responsible for enhanced L-VDCC opening and/or their upregulation in hypertensive animals. In conclusions, BP response to nifedipine is proportional to the vasoconstrictor activity exerted by both SNS and RAS, indicating a key importance of these two pressor systems for actual L-VDCC opening necessary for BP maintenance., J. Zicha ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
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
This study investigated whether endothelin (ET)-1-induced increase in myocardial distensibility is preserved in heart failure (HF) and whether it is modulated by nitric oxide (NO) and prostaglandins. New Zealand white rabbits were treated with doxorubicin (1 mg/kg, intravenously twice a week for 8 weeks, DOX-HF group) or saline (control group). Effects of ET-1 (0.1, 1, 10 nM) were tested in papillary muscles from the DOX-HF group and a control group in the presence of: i) intact endocardial endothelium (EE); ii) damaged EE; iii) NG-nitro-L-arginine (L-NNA; NO synthase inhibitor), and iv) indomethacin (INDO; cyclooxygenase inhibitor). In the presence of an intact EE, ET-1 promoted concentration-dependent positive inotropic and lusitropic effects that were maintained after damaging the EE, in the presence of L-NNA or INDO and in the DOX-HF Group. ET-1 reduced resting tension at the end of the isometric twitch (increased diastolic distensibility) by 3.2±1.3 %, 6.0±1.6 % and 8.8±2.7 % (at 0.1, 1 and 10 nM, respectively), in muscles with intact EE, effect that was completely abolished after damaging EE, in the presence of L-NNA or INDO or in the DOX-HF Group. This study demonstrated that the increase in myocardial distensibility induced by ET-1 is absent in HF and is dependent of NO and prostaglandin release., C. Brás-Silva, D. Monteiro-Sousa, A. J. Duarte, M. Guerra, A. P. Fontes-Sousa, C. Moura, J. C. Areias, A. F. Leite-Moreira., and Obsahuje bibliografii a bibliografické odkazy
Nitric oxide (NO) is implicated in a wide variety of biological roles. NO is generated from three nitric oxide synthase (NOS) isoforms: neuronal (nNOS), inducible (iNOS), and endothelial (eNOS) all of which are found in the lung. While there are no isoform-specific inhibitors of NOS, the recent development and characterization of mice deficient in each of the NOS isoforms has allowed for more comprehensive study of the importance of NO in the lung circulation. Studies in the mouse have identified the role of NO from eNOS in modulating pulmonary vascular tone and in attenuating the development of chronic hypoxic pulmonary hypertension., K. A. Fagan, I. McMurtry, D. M. Rodman., and Obsahuje bibliografii
a1_The effect of lesions induced by bilateral intracerebroventricular (ICV) injection of quinolinate (250 nmol of QUIN/ventricle), a selective N-methyl-D-aspartate (NMDA) receptor agonist, on [3H]glutamate ([3H]Glu) binding to the main types of both ionotropic and metabotropic glutamate receptors (iGluR and mGluR) was investigated in synaptic membrane preparations from the hippocampi of 50-day-old rats. The membranes from QUIN injured brains revealed significantly lowered binding in iGluR (by 31 %) as well as in mGluR (by 22 %) as compared to the controls. Using selected glutamate receptor agonists as displacers of [3H]Glu binding we found that both the NMDA-subtype of iGluR and group I of mGluR are involved in this decrease of binding. Suppression of nitric oxide (NO) production by NG-nitro-L-arginine (50 nmol of NARG/ventricle) or the increase of NO generation by 3-morpholinylsydnoneimine (5 nmol of SIN-1/ventricle) failed to alter [3H]Glu or [3H]CPP (3-((D)-2-carboxypiperazin-4-yl)-[1,2-3H]-propyl-1-phosphonic acid; NMDA-antagonist) binding declines caused by QUIN-lesions. Thus, our findings indicate that both the NMDA-subtype of iGluR and group I of mGluR are susceptible to the QUIN-induced neurodegeneration in the rat hippocampus. However, the inhibition of NO synthesis did not reveal any protective action in the QUIN-evoked, NMDA-receptor mediated decrease of [3H]Glu binding., a2_Therefore, the additional mechanisms of QUIN action, different from direct NMDA receptor activation/NO production (e.g. lipid peroxidation induced by QUIN-Fe-complexes) cannot be excluded., V. Lisý, F. Šťastný., and Obsahuje bibliografii
Recent data suggest that there is interaction between peripheral angiotensin II and nitric oxide. However, sparse information is available on the mutual interaction of these two compounds in the brain. The potential intercourse of nitric oxide with brain neuropeptides needs to be substantiated by assessing its local production and gene expression of the synthesizing enzymes involved. The aim of the present study was to evaluate whether the gene expression of brain nitric oxide synthase (bNOS) is related to the sites of gene expression of different components of the rat brain renin angiotensin system (renin, angiotensin converting enzyme (ACE) or angiotensin receptors of AT1 and AT2 subtypes). The levels of corresponding mRNAs were measured and correlated in nine structures of adult rat brain (hippocampus, amygdala, septum, thalamus, hypothalamus, cortex, pons, medulla and cerebellum). As was expected, positive correlation was observed between renin and angiotensin-converting enzyme mRNAs. Moreover, a significant correlation was found between brain NO synthase and AT1 receptor mRNAs, but not with mRNA of the AT2 receptor, ACE and renin. Parallel distribution of mRNAs coding for bNOS and AT1 receptors in several rat brain structures suggests a possible interaction between brain angiotensin II and nitric oxide, which remains to be definitely demonstrated by other approaches., O. Križanová, A. Kiss, Ľ. Žáčiková, D. Ježová., and Obsahuje bibliografii
NO concentration in the femoral artery and femoral vein of anesthetized dogs was found to be 154.2± 5.6 nM and 90.0± 12 nM, respectively. Inhibition of NO synthase (NOS) slightly decreased the basal NO concentration in femoral artery from 154.2± 5.6 to 137.2± 3.3 nM. Acetylcholine-induced increase in NO concentration was slightly but still significantly attenuated, suggesting that very probably L-NAME did not inhibit all sources of nitric oxide (NO). Local NOS inhibition in the posterior hypothalamus dose-dependently increased systemic blood pressure (BP) in rats. Short-term general NOS inhibition in anesthetized dogs increased diastolic BP but not systolic BP. The heart rate after one-hour down-fluctuation returned to initial values. Proteosynthesis in the myocardium and both branches of the left coronary artery increased, but this was not supported by polyamines, since the activity of ornithine decarboxylase declined. Long-term general NOS inhibition elicited a sustained BP increase, a decrease in heart rate, cardiac hypertrophy and an increase in wall thickness of the coronary and carotid artery. The results indicate that NO deficiency itself plays a role in proteosynthesis and cardiac hypertrophy, in spite of relatively small increase in diastolic blood pressure and no change in systolic blood pressure, at least after an acute L-NAME administration. The hypotension response to acetylcholine and bradykinin studied in anesthetized NO-compromised rats, was unexpectedly enhanced. The elucidation of this paradoxical phenomenon will require further experiments., M. Gerová., and Obsahuje bibliografii
The protective effect of therapeutic hypothermia in cardiac arrest survivors (CAS) has been previously well documented. Animal studies have indicated that attenuation of tissue oxidative stress (OS) may be involved in the mechanisms that lead to the beneficial effect of hypothermia. The extent of OS and nitric oxide (NO) production in adult CAS treated with endovascular hypothermia is, however, unknown. A total of 11 adult patients who experienced cardiac arrest out of hospital were included in the present study, and all were treated with mild hypothermia using the Thermogard XP (Alsius, USA) endovascular system. A target core temperature of 33 °C was maintained for 24 hours, with a subsequent rewarming rate of 0.15 °C per hour, followed by normothermia at 36.8 °C. Blood samples for the measurement of nitrotyrosine and nitrate/nitrite levels were drawn at admission and every 6 hours thereafter for two days. During the hypothermic period, the levels of nitrotyrosine and nitrates/nitrites were comparable with baseline values. During the rewarming period, serum levels of both parameters gradually increased and, during the normothermic period, the levels were significantly higher compared with hypothermic levels (nitrotyrosine, P<0.001; nitrates/nitrites, P<0.05). In our study, significantly lower levels of nitrotyrosine and nitrates/nitrites were demonstrated during hypothermia compared with levels during the normothermic period in adult CAS. These data suggest that attenuation of OS and NO production may be involved in the protective effect of hypothermia in adult CAS., A. Krüger ... [et al.]., and Obsahuje seznam literatury
Glutamate is the main excitatory neurotransmitter in the brain and ionotropic glutamate receptors mediate the majority of excitatory neurotransmission (Dingeldine et al. 1999). The high level of glutamatergic excitation allows the neonatal brain (the 2 nd postnatal week in rat) to develop quickly but it also makes it highly prone to age-specific seizures that can cause lifelong neurological and cognit ive disability (Haut et al. 2004). There are three types of ionotropic glutamate receptors (ligand-gated ion channels) named according to their prototypic agonists: N- methyl-D-aspartate (NMDA), 2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl) propanoic acid (AMPA) and kainate (KA). During early stages of postnatal development glutamate receptors of NMDA and AMPA type undergo intensive functional changes owing to modifications in their subunit composition (Carter et al. 1988, Watanabe et al. 1992, Monyer et al. 1994, Wenzel et al. 1997, Sun et al. 1998, Lilliu et al. 2001, Kumar et al. 2002, Matsuda et al. 2002, Wee et al. 2008, Henson et al. 2010, Pachernegg et al. 2012, Paoletti et al. 2013). Participation and role of these receptors in mechanisms of seizures and epilepsy became one of the main targets of intensive investigation (De Sarro et al. 2005, Di Maio et al. 2012, Rektor 2013). LiCl/Pilocarpine (LiCl/Pilo) induced status epilepticus is a model of severe seizures resulting in development temporal lobe epilepsy (TLE). This review will consider developmental changes and contribution of NMDA and AMPA receptors in LiCl/Pilo model of status epilepticus in immature rats., E. Szczurowska, P. Mareš., and Obsahuje bibliografii a bibliografické odkazy