Q96200785
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The sympathetic nerve activity (SNA) is augmented in hypertension. SNA is regulated by neuronal nitric oxide synthase (nNOS) or endothelial nitric oxide synthase (eNOS) activity in hypothalamic paraventricular nuclei (PVN) and/or brainstem rostral ventrolateral medulla. High nNOS or eNOS activity within these brain regions lowers the SNA, whereas low cerebral nNOS and/or eNOS activity causes SNA augmentation. We hypothesize that the decreased cerebral nNOS/eNOS activity, which allows the enhancement of SNA, leads to the augmentation of renal eNOS/nNOS activity. Similarly, when the cerebral nNOS/eNOS activity is increased and SNA is suppressed, the renal eNOS/nNOS activity is suppressed as well. The activation of endothelial alpha(2)-adrenoceptors, may be a possible mechanism involved in the proposed regulation. Another possible mechanism might be based on nitric oxide, which acts as a neurotransmitter that tonically activates afferent renal nerves, leading to a decreased nNOS activity in PVN. Furthermore, the importance of the renal nNOS/eNOSactivity during renal denervation is discussed. In conclusion, the presented hypothesis describes the dual organ-specific role of eNOS/nNOS activity in blood pressure regulation and suggests possible connection between cerebral NOS and renal NOS via activation or inhibition of SNA, which is an innovative idea in the concept of pathophysiology of hypertension.
- MeSH
- hypertenze enzymologie patofyziologie MeSH
- krevní tlak * MeSH
- ledviny enzymologie inervace MeSH
- lidé MeSH
- mozek enzymologie MeSH
- oxid dusnatý metabolismus MeSH
- sympatický nervový systém patofyziologie MeSH
- synthasa oxidu dusnatého, typ I metabolismus MeSH
- synthasa oxidu dusnatého, typ III metabolismus 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
Východiská: Kožné metastázy sú prítomné u 1–9 % onkologických pacientov. V zriedkavých prípadoch sa môžu kožné metastázy manifestovať ako inflamatórne lézie a sú diagnostikované ako inflamatórne kožné metastázy (ICM). ICM pri karcinóme pľúc sú extrémne zriedkavé a často sú nesprávne diagnostikované. Prípad: V práci referujeme 55-ročného muža s metastatickým adenokarcinómom pľúc s kostnými metastázami v axiálnom skelete a ľavom humeru diagnostikovaného v auguste 2008. Pacient podstúpil 6 cyklov paliatívnej chemoterapie cisplatinou a gemcitabínom s dosiahnutím regresie nádoru. O päť mesiacov neskôr sa u pacienta objavila progredujúca bolesť v ľavom ramene s erytematóznou, neostro ohraničenou léziou s inflamatórnym vzhľadom. Bola stanovená diagnóza kožnej infekcie a následne bola zahájená antibiotická liečba, avšak bez efektu. Výsledky: Kožná biopsia odhalila infiltráciu kože slabo diferencovaným karcinómom kompatibilným s primárnym pľúcnym nádorom. U pacienta bola zahájená druhá línia liečby docetaxelom, avšak stav sa rýchlo zhoršoval a pacient zomrel dva mesiace od prvého výskytu ICM. Záver: Metastáza pľúcneho karcinómu môže byť jednou z príčin inflamatórnych kožných lézií u pacientov s nádorovým ochorením a prítomnosť týchto metastáz je potrebné zvážiť u pacientov s perzistujúcimi kožnými léziami neodpovedajúcimi na antibiotickú liečbu.
Backgrounds: Skin metastases are present in 1– 9% of cancer patients. In rare cases, skin metastases can manifest as lesions with signs of infl ammation and are diagnosed as infl ammatory cutaneous metastases (ICM). ICM in lung cancer are extremely rare and often misdiagnosed. Patients and Methods: We report on a 55-year old man with metastatic lung adenocarcinoma and bone metastases in the axial skeleton and left humerus diagnosed in August 2008. He underwent 6 cycles of palliative chemotherapy with cisplatin and gemcitabine, obtaining a minor response. Five months later, he experienced increasing pain in his left arm, with erythematous oedematous lesion with poorly defi ned margins and an infl ammatory appearance. A diagnosis of skin infection was made and he was treated by antibio tic therapy without improvement. Results: Skin bio psy revealed skin infi ltration by poorly diff erentiated carcinoma compatible with a primary lung tumour. He was started on second line therapy with docetaxel, however, the patient‘s status deteriorated rapidly and he died two months after the fi rst appearance of ICM. Conclusion: Metastasis of lung carcinoma could be one of the causes of infl ammatory skin lesions in cancer patients and these metastases should be considered in cancer patients with persisting cutaneous lesions with signs of infl ammation and no response to antibio tic therapy
- MeSH
- adenokarcinom patologie sekundární MeSH
- kůže patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory kostí sekundární MeSH
- nádory kůže patologie sekundární MeSH
- nádory plic patologie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
Blood pressure (BP) level results from the balance of vasoconstrictors (mainly sympathetic nervous system) and vasodilators (predominantly nitric oxide and endothelium-derived hyperpolarizing factor). Most of the forms of experimental hypertension are associated with sympathetic hyperactivity and endothelial dysfunction. It is evident that nitric oxide and norepinephrine are antagonists in the control of calcium influx through L-type voltage-dependent calcium channels (L-VDCC). Their effects on L-VDCC are mediated by cGMP and cAMP, respectively. Nevertheless, it remains to determine whether these cyclic nucleotides have direct effects on L-VDCC or they act through a modulation of calcium-activated K(+) and Cl(-) channels which influence membrane potential. Rats with genetic or salt hypertension are characterized by a relative (but not absolute) NO deficiency compared to the absolute enhancement of sympathetic vasoconstriction. This dysbalance of vasoconstrictor and vasodilator systems in hypertensive animals is reflected by greater calcium influx through L-VDCC susceptible to the inhibition by nifedipine. However, when the modulatory influence of cyclic nucleotides is largely attenuated by simultaneous ganglionic blockade and NO synthase inhibition, BP of spontaneously hypertensive rats remains still elevated compared to normotensive rats due to augmented nifedipine-sensitive BP component. It remains to determine why calcium influx through L-VDCC of hypertensive rats is augmented even in the absence of modulatory influence of major vasoactive systems (sympathetic nervous system, nitric oxide).
- MeSH
- alfa-adrenergní receptory metabolismus MeSH
- chloridové kanály metabolismus MeSH
- financování organizované MeSH
- gating iontového kanálu MeSH
- genetická predispozice k nemoci MeSH
- hypertenze etiologie metabolismus patofyziologie MeSH
- krevní tlak MeSH
- krysa rodu rattus MeSH
- kuchyňská sůl škodlivé účinky MeSH
- lidé MeSH
- modely nemocí na zvířatech MeSH
- nukleotidy cyklické metabolismus MeSH
- oxid dusnatý metabolismus MeSH
- potkani inbrední SHR MeSH
- proteiny vázající GTP - alfa-podjednotky Gi-Go metabolismus MeSH
- sympatický nervový systém patofyziologie MeSH
- vápník metabolismus MeSH
- vápníková signalizace MeSH
- vápníkové kanály - typ L metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- zvířata MeSH
- Publikační typ
- přehledy MeSH
- MeSH
- arteriae mesentericae patologie účinky léků MeSH
- arterie patologie účinky léků MeSH
- experimenty na zvířatech MeSH
- financování organizované MeSH
- králíci krev MeSH
- krevní oběh fyziologie účinky léků MeSH
- NG-nitroargininmethylester diagnostické užití MeSH
- oxid dusnatý biosyntéza MeSH
- ucho fyziologie krevní zásobení MeSH
- zvířata MeSH
- Check Tag
- králíci krev MeSH
- zvířata MeSH
- Publikační typ
- abstrakty MeSH
- MeSH
- acetylcholin izolace a purifikace metabolismus MeSH
- cévní endotel metabolismus patofyziologie účinky léků MeSH
- experimentální diabetes mellitus farmakoterapie MeSH
- experimenty na zvířatech MeSH
- financování organizované MeSH
- glykosaminoglykany krev metabolismus MeSH
- hodnocení léčiv metody využití MeSH
- komplikace diabetu krev metabolismus MeSH
- potkani Wistar MeSH
- streptozocin farmakologie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- abstrakty MeSH