Reactive oxygen species are an important element of redox regulation in cells and tissues. During physiological processes, molecules undergo chemical changes caused by reduction and oxidation reactions. Free radicals are involved in interactions with other molecules, leading to oxidative stress. Oxidative stress works two ways depending on the levels of oxidizing agents and products. Excessive action of oxidizing agents damages biomolecules, while a moderate physiological level of oxidative stress (oxidative eustress) is necessary to control life processes through redox signaling required for normal cellular operation. High levels of reactive oxygen species (ROS) mediate pathological changes. Oxidative stress helps to regulate cellular phenotypes in physiological and pathological conditions. Nrf2 (nuclear factor erythroid 2-related factor 2, NFE2L2) transcription factor functions as a target nuclear receptor against oxidative stress and is a key factor in redox regulation in hypertension and cardiovascular disease. Nrf2 mediates transcriptional regulation of a variety of target genes. The Keap1-Nrf2-ARE system regulates many detoxification and antioxidant enzymes in cells after the exposure to reactive oxygen species and electrophiles. Activation of Nrf2/ARE signaling is differentially regulated during acute and chronic stress. Keap1 normally maintains Nrf2 in the cytosol and stimulates its degradation through ubiquitination. During acute oxidative stress, oxidized molecules modify the interaction of Nrf2 and Keap1, when Nrf2 is released from the cytoplasm into the nucleus where it binds to the antioxidant response element (ARE). This triggers the expression of antioxidant and detoxification genes. The consequence of long-term chronic oxidative stress is activation of glycogen synthase kinase 3beta (GSK-3beta) inhibiting Nrf2 activity and function. PPARgamma (peroxisome proliferator-activated receptor gamma) is a nuclear receptor playing an important role in the management of cardiovascular diseases, hypertension and metabolic syndrome. PPARgamma targeting of genes with peroxisome proliferator response element (PPRE) has led to the identification of several genes involved in lipid metabolism or oxidative stress. PPARgamma stimulation is triggered by endogenous and exogenous ligands - agonists and it is involved in the activation of several cellular signaling pathways involved in oxidative stress response, such as the PI3K/Akt/NOS pathway. Nrf2 and PPARgamma are linked together with their several activators and Nrf2/ARE and PPARgamma/PPRE pathways can control several types of diseases.
- MeSH
- antioxidační responzivní elementy MeSH
- faktor 2 související s NF-E2 metabolismus MeSH
- hypertenze metabolismus patofyziologie MeSH
- kardiovaskulární nemoci metabolismus patofyziologie MeSH
- KEAP-1 metabolismus MeSH
- krevní tlak * MeSH
- lidé MeSH
- oxidační stres * MeSH
- PPAR gama metabolismus MeSH
- reaktivní formy kyslíku metabolismus MeSH
- signální transdukce MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
We investigated whether polyethylene glycol-coated Fe3O4 nanoparticles (IONs), acute stress and their combination modifies vascular functions, nitric oxide synthase (NOS) activity, mean arterial pressure (MAP) as well as hepcidin and ferritin H gene expressions in Wistar-Kyoto rats. Rats were divided into control, ION-treated rats (1 mg Fe/kg i.v.), repeated acute air-jet stress-exposed rats and IONs-and-stress co-exposed rats. Maximal acetylcholine (ACh)-induced and sodium nitroprusside (SNP)-induced relaxations in the femoral arteries did not differ among the groups. IONs alone significantly elevated the N?-nitro-L-arginine methyl ester (L-NAME)-sensitive component of ACh-induced relaxation and reduced the sensitivity of vascular smooth muscle cells to SNP. IONs alone also elevated NOS activity in the brainstem and hypothalamus, reduced NOS activity in the kidneys and had no effect in the liver. Acute stress alone failed to affect vascular function and NOS activities in all the tissues investigated but it elevated ferritin H expression in the liver. In the ION-and-stress group, NOS activity was elevated in the kidneys and liver, but reduced in the brainstem and hypothalamus vs. IONs alone. IONs also accentuated air-jet stress-induced MAP responses vs. stress alone. Interestingly, stress reduced ION-originated iron content in blood and liver while it was elevated in the kidneys. In conclusion, the results showed that 1) acute administration of IONs altered vascular function, increased L-NAME-sensitive component of ACh-induced relaxation and had tissue-dependent effects on NOS activity, 2) ION effects were considerably reduced by co-exposure to repeated acute stress, likely related to decrease of ION-originated iron in blood due to elevated decomposition and/or excretion.
- MeSH
- cévní endotel účinky léků metabolismus MeSH
- fyziologický stres účinky léků MeSH
- krysa rodu rattus MeSH
- magnetické nanočástice oxidů železa aplikace a dávkování chemie MeSH
- oxid dusnatý biosyntéza metabolismus MeSH
- potkani inbrední WKY MeSH
- synthasa oxidu dusnatého metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Malígny melanóm je agresívne ochorenie s vysokým potenciálom metastazovania do ktoréhokoľvej orgánu, vrátane srdca. Prezentujeme prípad pacienta, u ktorého sa po 16 rokoch od extirpácie kožného melanómu manifestovala srdcovým zlyhaním generalizácia ochorenia do srdca. Diagnóza bola stanovená po smrti. Štúdie nekroptických materiálov ukazujú, že malígny melanóm metastazuje do srdca asi v 50–64 % prípadov, diagnóza je vzhľadom na chýbanie špecifických klinických príznakov a limitovanú výťažnosť zobrazovacích metód zväčša stanovená po smrti. Preto u všetkých pacientov s anamnézou malígneho melanónu je potrebné pri akýchkoľvek kardiálnych príznakoch na možnosť generalizácie ochorenia do srdca myslieť.
The malignant melanoma is an aggressive disease with a high potential of spreading metastases to any organ, heart included. We are presenting a patient, by whom a generalisation of the heart disease was manifested by a heart failure sixteen years after extirpation of malignant melanoma. The diagnose was made after patient´s death. Studies of necroptic material show that malignant melanoma creates metastases to heart in 50–64% of the cases. However, because of the default of specific clinical cases and the limited possibilities of using imaging techniques the diagnose is mostly declared after the death of the patient. That is why it is necessary in patients with history taking of malignant melanoma to think about tumour generalisation by every cardiac symptom.
- MeSH
- antibakteriální látky aplikace a dávkování terapeutické užití MeSH
- antioxidancia MeSH
- biochemická analýza krve MeSH
- dialýza MeSH
- diferenciální diagnóza MeSH
- diuretika MeSH
- fatální výsledek MeSH
- furosemid aplikace a dávkování terapeutické užití MeSH
- jaterní cirhóza diagnóza etiologie MeSH
- lidé MeSH
- melanom * etiologie terapie MeSH
- metastázy nádorů * MeSH
- nádory prostaty MeSH
- nádory sleziny sekundární MeSH
- nádory srdce sekundární MeSH
- otitida MeSH
- pitva MeSH
- renální insuficience MeSH
- senioři MeSH
- silymarin aplikace a dávkování terapeutické užití MeSH
- spironolakton aplikace a dávkování terapeutické užití MeSH
- splenomegalie MeSH
- srdeční selhání diagnóza etiologie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- kazuistiky 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
This study investigated the contribution of reactive oxygen species (ROS) to blood pressure regulation in conscious adult male Wistar rats exposed to acute stress. Role of ROS was investigated in rats with temporally impaired principal blood pressure regulation systems using ganglionic blocker pentolinium (P, 5 mg/kg), angiotensin converting enzyme inhibitor captopril (C, 10 mg/kg), nitric oxide synthase inhibitor L-NAME (L, 30 mg/kg) and superoxide dismutase mimeticum tempol (T, 25 mg/kg). Mean arterial pressure (MAP) was measured by the carotid artery catheter and inhibitors were administered intravenously. MAP was disturbed by a 3-s air jet, which increased MAP by 35.2+/-3.0 % vs. basal MAP after the first exposure. Air jet increased MAP in captopril- and tempol-treated rats similarly as observed in saline-treated rats. In pentolinium-treated rats stress significantly decreased MAP vs. pre-stress value. In L-NAME-treated rats stress failed to affect MAP significantly. Treatment of rats with P+L+C resulted in stress-induced MAP decrease by 17.3+/-1.3 % vs. pre-stress value and settling time (20.1+/-4.2 s). In P+L+C+T-treated rats stress led to maximal MAP decrease by 26.4+/-2.2 % (p<0.005 vs. P+L+C) and prolongation of settling time to 32.6+/-3.3 s (p<0.05 vs. P+L+C). Area under the MAP curve was significantly smaller in P+L+C-treated rats compared to P+L+C+T-treated ones (167+/-43 vs. 433+/-69 a.u., p<0.008). In conclusion, in rats with temporally impaired blood pressure regulation, the lack of ROS resulted in greater stress-induced MAP alterations and prolongation of time required to reach new post-stress steady state.
- MeSH
- krevní tlak * MeSH
- krysa rodu rattus MeSH
- potkani Wistar MeSH
- psychický stres patofyziologie MeSH
- reaktivní formy kyslíku metabolismus MeSH
- sympatický nervový systém patofyziologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
As wine polyphenols were shown to possess many positive effects in mammals, including improvement of vascular function, this study investigated the effect of the Slovak Alibernet red wine extract (AWE) on blood pressure and vascular function in young normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. Six weeks old, male, WKY and SHR were treated with AWE for three weeks at the dose of 24.2 mg/kg/day. Blood pressure (BP), determined by tail-cuff plethysmography, was significantly elevated in SHR vs. WKY and AWE failed to affect it. Lipid peroxidation was evaluated by determination of thiobarbituric acid-reactive substances. Vascular function was assessed in rings of the femoral artery using Mulvany-Halpern's myograph. Maximal endothelium-dependent acetylcholine (ACh)-induced relaxation was reduced in control SHR vs. WKY rats by approximately 9.3 %, which was associated with a significant decrease of its NO-independent component. AWE failed to affect maximal ACh-induced relaxation, both its NO-dependent and independent components, compared to controls of the same genotype. AWE however reduced lipid peroxidation in the left ventricle of both WKY and SHR and in the liver of SHR. In conclusion, three-week administration of AWE failed to reduce BP and to improve endothelial function in the femoral arteries of both genotypes investigated.
- MeSH
- cévní endotel účinky léků patofyziologie MeSH
- cévní rezistence účinky léků MeSH
- hypertenze farmakoterapie etiologie patofyziologie MeSH
- krevní tlak účinky léků MeSH
- krysa rodu rattus MeSH
- neúspěšná terapie MeSH
- onemocnění periferních arterií komplikace farmakoterapie patofyziologie MeSH
- potkani inbrední SHR MeSH
- potkani inbrední WKY MeSH
- rostlinné extrakty aplikace a dávkování MeSH
- stilbeny aplikace a dávkování MeSH
- víno MeSH
- výsledek terapie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
This study examined nitric oxide (NO) production, oxidative load and endothelium-dependent relaxation (NO-dependent and NO-independent) in adult male borderline hypertensive (BHR) and spontaneously hypertensive (SHR) rats as compared to normotensive Wistar-Kyoto (WKY) rats. Systolic blood pressure (BP) was determined by tail-cuff. NO production was determined by conversion of [(3)H]-L-arginine. Conjugated dienes (CD) and concentrations of thiobarbituric acid-reactive substances (TBARS) were measured for assessment of oxidative load. Vascular function was investigated in rings of the femoral artery (FA) using a wire myograph. BP of WKY, BHR and SHR was 106+/-2, 143+/-3 and 191+/-3 mm Hg, respectively (p<0.01 for each). Significant left ventricle (LV) hypertrophy and elevated levels of CD and TBARS in the LV were present in BHR and SHR as compared to WKY. NO production was elevated significantly in the aorta of BHR and SHR vs. WKY as well as in the LV of SHR vs. WKY. Acetylcholine (ACh)-induced relaxation of the FA was reduced significantly in both BHR and SHR vs. WKY. The NO-dependent component of ACh-induced relaxation had increasing tendency in hypertensive groups and it correlated positively with BP. The NO-independent component of vasorelaxation was reduced significantly in BHR and SHR vs. WKY and it correlated negatively with BP. In conclusion, the results showed that endothelial dysfunction in the experimental model of borderline hypertensive and hypertensive rats is NO-independent. The results suggest that borderline hypertension represents a risk of other cardiovascular disorders which is qualitatively similar to that of fully developed hypertension.
- MeSH
- arteria femoralis patofyziologie MeSH
- cévní endotel patofyziologie MeSH
- hypertenze etiologie patofyziologie MeSH
- krevní tlak MeSH
- krysa rodu rattus MeSH
- onemocnění periferních arterií komplikace patofyziologie MeSH
- oxid dusnatý metabolismus MeSH
- potkani inbrední SHR MeSH
- potkani inbrední WKY MeSH
- tuhost cévní stěny MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
