The cardioprotective effect of ischemic preconditioning (IPC) and ischemic postconditioning (IPoC) in adult hearts is mediated by nitric oxide (NO). During the early developmental period, rat hearts exhibit higher resistance to ischemia-reperfusion (I/R) injury, contain higher levels of serum nitrates, and their resistance cannot be further increased by IPC or IPoC. NOS blocker (L-NAME) lowers their high resistance. Wistar rat hearts (postnatal Days 1 and 10) were perfused according to Langendorff and exposed to 40 min of global ischemia followed by reperfusion with or without IPoC. NO and reactive oxygen species donors (DEA-NONO, SIN-1) and L-NAME were administered. Tolerance to ischemia decreased between Days 1 and 10. DEA-NONO (low concentrations) significantly increased tolerance to I/R injury on both Days 1 and 10. SIN-1 increased tolerance to I/R injury on Day 10, but not on Day 1. L-NAME significantly reduced resistance to I/R injury on Day 1, but actually increased resistance to I/R injury on Day 10. Cardioprotection by IPoC on Day 10 was not affected by either NO donors or L-NAME. It can be concluded that resistance of the neonatal heart to I/R injury is NO dependent, but unlike in adult hearts, cardioprotective interventions, such as IPoC, are most likely NO independent.

• MeSH
• donory oxidu dusnatého farmakologie   MeSH
• ischemické přivykání metody   MeSH
• ischemický postconditioning * metody   MeSH
• krysa rodu rattus MeSH
• molsidomin farmakologie   analogy a deriváty   MeSH
• myokard metabolismus   MeSH
• NG-nitroargininmethylester * farmakologie   MeSH
• novorozená zvířata * MeSH
• oxid dusnatý * metabolismus   MeSH
• potkani Wistar * MeSH
• reperfuzní poškození myokardu * prevence a kontrola   metabolismus   MeSH
• srdce účinky léků   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Hypertension is one of the most prevalent and powerful contributors of cardiovascular diseases. Malignant hypertension is a relatively rare but extremely severe form of hypertension accompanied with heart, brain, and renal impairment. Resveratrol, a recently described grape-derived, polyphenolic antioxidant molecule, has been proposed as an effective agent in the prevention of cardiovascular diseases. This study was designed to examine chronic resveratrol administration on blood pressure, oxidative stress, and inflammation, with special emphasis on cardiac structure and function in two models of experimental hypertension. The experiments were performed in spontaneously (SHRs) and malignantly hypertensive rats (MHRs). The chronic administration of resveratrol significantly decreased blood pressure in both spontaneously and malignant hypertensive animals. The resveratrol treatment ameliorated morphological changes in the heart tissue. The immunohistochemistry of the heart tissue after resveratrol treatment showed that both TGF-β and Bax were not present in the myocytes of SHRs and were present mainly in the myocytes of MHRs. Resveratrol suppressed lipid peroxidation and significantly improved oxidative status and release of NO. These results suggest that resveratrol prevents hypertrophic and apoptotic consequences induced by high blood pressure with more pronounced effects in malignant hypertension.

• MeSH
• antiflogistika farmakologie   terapeutické užití   MeSH
• antioxidancia terapeutické užití   MeSH
• apoptóza * účinky léků   MeSH
• hemodynamika účinky léků   MeSH
• hypertenze maligní farmakoterapie   enzymologie   patologie   patofyziologie   MeSH
• kardiotonika farmakologie   terapeutické užití   MeSH
• látky reagující s kyselinou thiobarbiturovou metabolismus   MeSH
• myokard patologie   MeSH
• NG-nitroargininmethylester chemie   farmakologie   MeSH
• oxidace-redukce MeSH
• potkani inbrední SHR MeSH
• protein X asociovaný s bcl-2 metabolismus   MeSH
• resveratrol chemie   farmakologie   terapeutické užití   MeSH
• srdeční komory účinky léků   patologie   patofyziologie   MeSH
• tělesná hmotnost účinky léků   MeSH
• velikost orgánu účinky léků   MeSH
• zánět komplikace   farmakoterapie   MeSH
• zvířata MeSH
• Check Tag
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

The renin-angiotensin-aldosterone system (RAAS) is a dominant player in several cardiovascular pathologies. This study investigated whether alterations induced by l-NAME, (NLG)-nitro-l-arginine methyl ester, a nitric oxide synthase inhibitor, and the protective effect of melatonin are associated with changes in the RAAS. Four groups of 3-month-old male Wistar rats (n = 10) were treated as follows for four weeks: untreated controls, rats treated with melatonin (10 mg/kg/day), rats treated with l-NAME (40 mg/kg/day), and rats treated with l-NAME + melatonin. l-NAME administration led to hypertension and left ventricular (LV) fibrosis in terms of enhancement of soluble, insoluble and total collagen concentration and content. Melatonin reduced systolic blood pressure enhancement and lowered the concentration and content of insoluble and total collagen in the LV. The serum concentration of angiotensin (Ang) 1-8 (Ang II) and its downstream metabolites were reduced in the l-NAME group and remained unaltered by melatonin. The serum aldosterone level and its ratio to Ang II (AA2-ratio) were increased in the l-NAME group without being modified by melatonin. We conclude that l-NAME-hypertension is associated with reduced level of Ang II and its downstream metabolites and increased aldosterone concentration and AA2-ratio. Melatonin exerts its protective effect in l-NAME-induced hypertension without affecting RAAS.

• MeSH
• hypertenze * chemicky indukované   metabolismus   patofyziologie   prevence a kontrola   MeSH
• krevní tlak účinky léků   MeSH
• krysa rodu rattus MeSH
• melatonin farmakologie   MeSH
• NG-nitroargininmethylester škodlivé účinky   farmakologie   MeSH
• potkani Wistar MeSH
• renin-angiotensin systém účinky léků   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Electric stimulation (ES) could induce contraction of intestinal smooth muscle. The aim of this study was to analyze the effects of ES on esophageal motility and the underlying mechanism in vivo. Twenty-eight rabbits were equipped with a pair of subserosa electrodes (connected to an electrical stimulator) in the lower segment of the esophagus. The ES signal consisted of bipolar rectangular pulse trains, lasting for 3 s, with different amplitudes (1 mA, 3 mA, 5 mA and 10 mA), and frequencies (10 Hz, 20 Hz and 50 Hz). The amplitude of the contraction was recognized by high-resolution manometry. The effect of ES was tested under anesthesia and following administration of atropine, phentolamine or L-NAME. ES induced esophageal contraction at the stimulated site. A statistically significant increase in esophageal pressure was observed when the stimulation amplitude was above 3 mA. The increase in esophageal pressure was associated with the amplitude of stimulus as well as the frequency. During stimulation, atropine, phentolamine and L-NAME had no effect on the increase of esophageal pressure induced by ES. These findings implied that ES induced esophageal contraction were not mediated via the NANC, adrenergic or cholinergic pathway. The amplitude of esophageal contraction was current and frequency dependent.

• MeSH
• alfa blokátory farmakologie   MeSH
• antagonisté muskarinových receptorů farmakologie   MeSH
• atropin farmakologie   MeSH
• elektrická stimulace * MeSH
• ezofágus účinky léků   fyziologie   MeSH
• fentolamin farmakologie   MeSH
• gastrointestinální motilita účinky léků   fyziologie   MeSH
• králíci MeSH
• manometrie MeSH
• NG-nitroargininmethylester farmakologie   MeSH
• poruchy motility jícnu patofyziologie   MeSH
• svalová kontrakce MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: The brain stem contains important nuclei that control cardiovascular function via the sympathetic nervous system (SNS), which is strongly influenced by nitric oxide. Its biological activity is also largely determined by oxygen free radicals. Despite many experimental studies, the role of AT1R-NAD(P)H oxidase-superoxide pathway in NO-deficiency is not yet sufficiently clarified. We determined changes in free radical signaling and antioxidant and detoxification response in the brain stem of young and adult Wistar rats during chronic administration of exogenous NO inhibitors. METHODS: Young (4 weeks) and adult (10 weeks) Wistar rats were treated with 7-nitroindazole (7-NI group, 10 mg/kg/day), a specific nNOS inhibitor, with NG-nitro-L-arginine-methyl ester (L-NAME group, 50 mg/kg/day), a nonspecific NOS inhibitor, and with drinking water (Control group) during 6 weeks. Systolic blood pressure was measured by non-invasive plethysmography. Expression of genes (AT1R, AT2R, p22phox, SOD and NOS isoforms, HO-1, MDR1a, housekeeper GAPDH) was identified by real-time PCR. NOS activity was detected by conversion of [3H]-L-arginine to [3H]-L-citrulline and SOD activity was measured using UV VIS spectroscopy. RESULTS: We observed a blood pressure elevation and decrease in NOS activity only after L-NAME application in both age groups. Gene expression of nNOS (youngs) and eNOS (adults) in the brain stem decreased after both inhibitors. The radical signaling pathway triggered by AT1R and p22phox was elevated in L-NAME adults, but not in young rats. Moreover, L-NAME-induced NOS inhibition increased antioxidant response, as indicated by the observed elevation of mRNA SOD3, HO-1, AT2R and MDR1a in adult rats. 7-NI did not have a significant effect on AT1R-NADPH oxidase-superoxide pathway, yet it affected antioxidant response of mRNA expression of SOD1 and stimulated total activity of SOD in young rats and mRNA expression of AT2R in adult rats. CONCLUSION: Our results show that chronic NOS inhibition by two different NOS inhibitors has age-dependent effect on radical signaling and antioxidant/detoxificant response in Wistar rats. While 7-NI had neuroprotective effect in the brain stem of young Wistar rats, L-NAME- induced NOS inhibition evoked activation of AT1R-NAD(P)H oxidase pathway in adult Wistar rats. Triggering of the radical pathway was followed by activation of protective compensation mechanism at the gene expression level.

• MeSH
• antioxidancia metabolismus   MeSH
• indazoly farmakologie   MeSH
• inhibitory enzymů farmakologie   MeSH
• krysa rodu rattus MeSH
• metabolická inaktivace * MeSH
• mozkový kmen účinky léků   metabolismus   MeSH
• NG-nitroargininmethylester farmakologie   MeSH
• oxid dusnatý nedostatek   MeSH
• potkani Wistar MeSH
• synthasa oxidu dusnatého antagonisté a inhibitory   MeSH
• věkové faktory MeSH
• volné radikály metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Nitric oxide (NO) chemistry inside the body is the most interesting part of its behavior. NO is involved in controlling blood pressure, and in transmitting nerve signals and a variety of other signaling processes. To explain the behavior of NO, it is necessary to determine its immediate concentration or observe time-dependent changes in its concentration. In Paramecium caudatum, NO is formed by calcium-dependent nNOS (NOS1)-like protein, which is distributed in the cytoplasm. NO synthesis affects the ciliary beat and consequent motility of cells and blocked NO synthesis reduces the ability of cells to move. The possibility of online coupling of microdialysis (of P. caudatum solution) with NO detection is demonstrated. Direct measurement of NO is carried out using dilute Bluestar® Forensic reagent (luminol-H2 O2 system; one of the NO detections is based upon the chemiluminescent reaction between NO and the luminol-H2 O2 system, which is specifically reactive to NO). The effect of a nitric oxide synthase inhibitor, NG-nitro-l-arginine methyl ester was observed. NO production was inhibited and the movement of P. caudatum was restricted. These effects were time dependent and after a specific time were reversed.

• MeSH
• inhibitory enzymů farmakologie   MeSH
• luminiscenční měření MeSH
• luminol chemie   MeSH
• mikrodialýza metody   MeSH
• NG-nitroargininmethylester farmakologie   MeSH
• oxid dusnatý analýza   chemie   metabolismus   MeSH
• Paramecium caudatum chemie   metabolismus   MeSH
• peroxid vodíku chemie   MeSH
• synthasa oxidu dusnatého antagonisté a inhibitory   MeSH
• Publikační typ
• časopisecké články MeSH

The endothelial barrier function is tightly controlled by a broad range of signaling cascades including nitric oxide-cyclic guanosine monophosphate (NO-cGMP) pathway. It has been proposed that disturbances in NO and cGMP production could interfere with proper endothelial barrier function. In this study, we assessed the effect of interferon-gamma (IFN-gamma), a pro-inflammatory cytokine, on NO and cGMP levels and examined the mechanisms by which NO and cGMP regulate the IFN-gamma-mediated HUVECs hyperpermeability. The flux of fluorescein isothiocyanate-labeled dextran across cell monolayers was used to study the permeability of endothelial cells. Here, we found that IFN-gamma significantly attenuated basal NO concentration and the increased NO levels supplied by a NO donor, sodium nitroprusside (SNP). Besides, application of IFN-gamma also significantly attenuated both the basal cGMP concentration and the increased cGMP production donated by a cell permeable cGMP analogue, 8-bromo-cyclic GMP (8-Br-cGMP). In addition, exposure of the cell monolayer to IFN-gamma significantly increased HUVECs basal permeability. However, L-NAME pretreatment did not suppress IFN-gamma-induced HUVECs hyperpermeability. L-NAME pretreatment followed by SNP or SNP pretreatment partially reduced IFN-gamma-induced HUVECs hyperpermeability. Pretreatment with a guanylate cyclase inhibitor, 6-anilino-5,8-quinolinedione (LY83583), led to a further increase in IFN-gamma-induced HUVECs hyperpermeability. The findings suggest that the mechanism underlying IFN-gamma-induced increased HUVECs permeability is partly related to the inhibition of NO production.

• MeSH
• donory oxidu dusnatého farmakologie   MeSH
• endoteliální buňky pupečníkové žíly (lidské) účinky léků   metabolismus   MeSH
• guanosinmonofosfát cyklický analogy a deriváty   metabolismus   farmakologie   MeSH
• guanylátcyklasa antagonisté a inhibitory   MeSH
• inhibitory enzymů farmakologie   MeSH
• interferon gama farmakologie   MeSH
• kapilární permeabilita účinky léků   MeSH
• lidé MeSH
• NG-nitroargininmethylester farmakologie   MeSH
• nitroprusid farmakologie   MeSH
• oxid dusnatý metabolismus   MeSH
• permeabilita buněčné membrány MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

This study was designated to estimate protective role of ETA and ETB receptor antagonist against endothelin 1 (ET-1)-induced oxidative stress in lungs and determine whether these effects are mediated by nitric oxide (NO) synthase. Experiments were performed on Wistar rats divided into the following groups: I - saline (0.9 % NaCl); II - ET-1 (3 microg/kg b.w.), III - BQ123 (1 mg/kg b.w.) + ET-1 (3 microg/kg b.w.), IV - BQ788 (3 mg/kg b.w.) + ET-1 (3 microg/kg b.w.), V - N-nitro-L-arginine methyl ester (L-NAME) (5 mg/kg b.w.) + ET-1 (3 microg/kg b.w.). ETA and ETB receptor antagonists or L-NAME were administered 30 min before ET-1 injection. The levels of the following substances were measured in the lungs homogenates: thiobarbituric acid reactive substances (TBARS), hydrogen peroxide (H(2)O(2)), reduced glutathione (GSH) and tumor necrosis factor-alpha (TNF-alpha). The results showed that ET-1 significantly increased TBARS, H(2)O(2) (respectively: p<0.001, p<0.02) and TNF-alpha levels (p<0.02) and decreased the GSH level (p<0.01) vs. CONTROL GROUP: On the other hand, prior administration of ETA receptor blocker (BQ123) significantly attenuated TBARS (p<0.01), H(2)O(2) (p<0.02), TNF-alpha (p<0.02) and increased GSH (p<0.02) levels vs. ET-1. However, prior administration of ETB receptor blocker BQ788 did not cause significant changes in the: TBARS, H(2)O(2) and TNF-alpha (p>0.05) levels, but significantly increased the GSH level and GSH/GSSG ratio (p<0.05). Administration of L-NAME significantly attenuated TBARS (p<0.001), H(2)O(2) (p<0.05), TNF-alpha (p<0.01) and increased GSH (p<0.05) levels vs. ET-1. In conclusion, we demonstrated that ET-1 induced oxidative stress in the lungs is mediated by ETA receptors. ETA receptor blockage inhibited generation of free radicals and TNF-alpha and ameliorated antioxidant properties. Moreover, generation of reactive oxygen species is mediated by NOS in the lungs.

• MeSH
• antagonisté endotelinového receptoru farmakologie   terapeutické užití   MeSH
• cyklické peptidy farmakologie   terapeutické užití   MeSH
• endotelin-1 MeSH
• glutathion metabolismus   MeSH
• náhodné rozdělení MeSH
• NG-nitroargininmethylester farmakologie   terapeutické užití   MeSH
• oligopeptidy farmakologie   terapeutické užití   MeSH
• oxidační stres účinky léků   MeSH
• peroxid vodíku metabolismus   MeSH
• peroxidace lipidů účinky léků   MeSH
• piperidiny farmakologie   terapeutické užití   MeSH
• plíce účinky léků   metabolismus   MeSH
• plicní nemoci etiologie   metabolismus   prevence a kontrola   MeSH
• potkani Wistar MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• receptor endotelinu A metabolismus   MeSH
• receptor endotelinu B metabolismus   MeSH
• synthasa oxidu dusnatého metabolismus   MeSH
• TNF-alfa metabolismus   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Two mechanisms contribute in the development of pulmonary hypertension in pulmonary embolism (PE) - obstruction of pulmonary blood vessels and vasoconstriction. We hypothesize that hypoxia, increased shear stress and/or activation of gathered leukocytes in the PE may cause a release of reactive oxygen species (ROS). Therefore our aim was to determine the influence of the ROS scavenger Tempol on pulmonary hypertension and to describe NO synthase activity and production of NO oxidative products (NOx) after PE. In general anesthesia sephadex microspheres suspended in PSS were applied in right jugular vein as the pulmonary microembolism. Than we measured in isolated salt solution-perfused lungs the changes in perfusion pressure, activity of NO synthase and NOx plasma concentration in 7 groups of rats: C: control group (n=5), CN: C + sodium nitroprusside (SN) (n=5), EN: PE + SN (n=5), ETN: Tempol + PE + SN (n=5), CL: C + L-NAME (n=5), EL: PE + L-NAME (n=5), ETL: Tempol + PE + L-NAME (n=5). Tempol was applied intraperitoneally before PE. Animals that received Tempol (groups TN, TL) had significantly lower basal perfusion pressure than those which did not receive Tempol (EN, EL). Overall we measured a higher decrease of perfusion pressure than in the control group (C) after application of SN. Administration of L-NAME after PE (EL) increased the pressure more than in the control group (NL). NOx concentration was higher after PE. We found that preventive administration of Tempol decreases the increase in perfusion pressure after PE. PE increased NO release and concentration of NOx.

• MeSH
• aktivace enzymů účinky léků   fyziologie   MeSH
• cyklické N-oxidy farmakologie   terapeutické užití   MeSH
• krevní tlak účinky léků   fyziologie   MeSH
• krysa rodu rattus MeSH
• mikrocirkulace účinky léků   fyziologie   MeSH
• NG-nitroargininmethylester farmakologie   MeSH
• orgánové kultury - kultivační techniky MeSH
• plicní embolie farmakoterapie   metabolismus   MeSH
• plicní oběh účinky léků   fyziologie   MeSH
• potkani Wistar MeSH
• reaktivní formy kyslíku antagonisté a inhibitory   metabolismus   MeSH
• scavengery volných radikálů farmakologie   terapeutické užití   MeSH
• spinové značení MeSH
• synthasa oxidu dusnatého antagonisté a inhibitory   metabolismus   MeSH
• vazokonstrikce účinky léků   fyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

We evaluated the effects of N(G)-nitro-L-arginine methylester (L-NAME) (50 mg/kg/day) and 7-nitroindazole (7NI) (10 mg/kg/day) administered from 10th-16th week of age either individually or together on cardiovascular system of Wistar rats and SHR. Systolic blood pressure (sBP) was measured weekly by the plethysmographic method. For morphological studies, the animals (n=10) were perfused with a fixative (120 mm Hg), and thoracic aorta and carotid and coronary arteries were processed for electron microscopy. For functional investigation (n=10), aortic rings were used in an organ bath. In Wistar rats, L-NAME evoked an increase of sBP; hypertrophy of the heart and arterial walls; an increase in cross-sectional areas (CSA) of endothelial cells (EC), muscle cells (SMC), extracellular matrix (ECM), and a decrease in acetylcholine-induced endothelial-dependent relaxation (EDR). 7NI evoked sBP-independent hypotrophy of the heart and arterial walls, a decrease in CSA of EC and SMC without affecting the CSA of ECM, and a mild decrease in acetylcholine-induced EDR. 7NI and L-NAME administered together evoked lower effect on BP and trophicity of the heart and all arteries, and a similar decrease in acetylcholine-induced EDR compared to L-NAME alone. In SHR, 7NI did not evoke any effect on the studied parameters.

• MeSH
• aorta thoracica účinky léků   enzymologie   patofyziologie   ultrastruktura   MeSH
• arteriae carotides účinky léků   enzymologie   patofyziologie   ultrastruktura   MeSH
• hypertenze farmakoterapie   enzymologie   patologie   patofyziologie   MeSH
• indazoly farmakologie   MeSH
• inhibitory enzymů farmakologie   MeSH
• kardiomegalie enzymologie   patologie   patofyziologie   prevence a kontrola   MeSH
• koronární cévy účinky léků   enzymologie   patofyziologie   ultrastruktura   MeSH
• krevní tlak účinky léků   MeSH
• modely nemocí na zvířatech MeSH
• NG-nitroargininmethylester farmakologie   MeSH
• potkani inbrední SHR MeSH
• potkani Wistar MeSH
• remodelace cév účinky léků   MeSH
• remodelace komor účinky léků   MeSH
• srdeční komory účinky léků   enzymologie   patologie   patofyziologie   MeSH
• synthasa oxidu dusnatého antagonisté a inhibitory   metabolismus   MeSH
• vazodilatace účinky léků   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH