The imbalance between nitric oxide (NO) and reactive oxygen species (ROS) production appears to be a common feature of experimental and human hypertension. Previously, different antioxidants and/or scavengers of oxygen free radicals were shown to activate nitric oxide synthase (NO synthase, NOS) and to increase the expression of both endothelial and neuronal NO synthase isoforms leading to blood pressure reduction. On the other hand, various antihypertensive drugs have been documented to possess antioxidant properties, which may contribute to their beneficial effect on blood pressure. This review is focused on the effects of antioxidant treatment in different models of experimental hypertension with a special attention to the prevention of oxidative damage and the augmentation of NO synthase activity and expression of NOS isoforms.

• MeSH
• antihypertenziva farmakologie   MeSH
• antioxidancia farmakologie   MeSH
• hypertenze metabolismus   MeSH
• krysa rodu rattus MeSH
• modely u zvířat MeSH
• oxid dusnatý biosyntéza   MeSH
• oxidace-redukce MeSH
• protein - isoformy metabolismus   MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• scavengery volných radikálů MeSH
• synthasa oxidu dusnatého metabolismus   MeSH
• volné radikály metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

This review concerns the role of nitric oxide (NO) in the pathogenesis of different models of experimental hypertension (NO-deficient, genetic, salt-dependent), which are characterized by a wide range of etiology. Although the contribution of NO may vary between different models of hypertension, a unifying characteristic of these models is the presence of oxidative stress that participates in the maintenance of elevated arterial pressure and seems to be a common denominator underlying endothelial dysfunction in various forms of experimental hypertension. Besides the imbalance between the endothelial production of vasorelaxing and vasoconstricting compounds as well as the relative insufficiency of vasodilator systems to compensate augmented vasoconstrictor systems, there were found numerous structural and functional abnormalities in blood vessels and heart of hypertensive animals. The administration of antihypertensive drugs, antioxidants and NO donors is capable to attenuate blood pressure elevation and to improve morphological and functional changes of cardiovascular system in some but not all hypertensive models. The failure to correct spontaneous hypertension by NO donor administration reflects the fact that sympathetic overactivity plays a key role in this form of hypertension, while NO production in spontaneously hypertensive rats might be enhanced to compensate increased blood pressure. A special attention should be paid to the modulation of sympathetic nervous activity in central and peripheral nervous system. These results extend our knowledge on the control of the balance between NO and reactive oxygen species production and are likely to be a basis for the development of new approaches to the therapy of diseases associated with NO deficiency.

• MeSH
• antihypertenziva farmakologie   MeSH
• antioxidancia farmakologie   MeSH
• cévní endotel metabolismus   patofyziologie   účinky léků   MeSH
• donory oxidu dusnatého farmakologie   MeSH
• financování organizované MeSH
• hypertenze MeSH
• hypertriglyceridemie genetika   komplikace   metabolismus   MeSH
• krevní tlak MeSH
• krysa rodu rattus MeSH
• kuchyňská sůl MeSH
• modely nemocí na zvířatech MeSH
• NG-nitroargininmethylester MeSH
• oxid dusnatý metabolismus   nedostatek   MeSH
• oxidační stres MeSH
• potkani inbrední SHR MeSH
• potkani Wistar MeSH
• psychický stres komplikace   metabolismus   MeSH
• sympatický nervový systém patofyziologie   MeSH
• synthasa oxidu dusnatého antagonisté a inhibitory   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH

Spontánne hypertenzný potkan (SHR) je najvhodnejším a najeastejšie používaným laboratórnym modelom pre výskum esenciálnej hypertenzie (EH). Patogenéza hypertenzie u SHR sa v mnohých aspektoch podobá na EH u 3udí. V 3udskej EH, a podobne u SHR, bola pozorovaná oslabená vazorelaxácia závislá od endotelu, tzv. endotelová dysfunkcia, ktorá prispieva k zvýšenej periférnej rezistencii. Endotelová dysfunkcia je pri hypertenzii charakterizovaná zmenami v produkcii a úeinku endotelových relaxaených (EDRFs) a konstriktorických (EDCFs) faktorov. Mechanizmus oslabenia relaxácie pri hypertenzii sa spája so znížením produkcie oxidu dusnatého (NO), znížením jeho biologickej dostupnosti alebo s nadprodukciou konstriktorických faktorov. Pri hypertenzii bola dokázaná zvýšená produkcia vo3ných kyslíkových radikálov, ktorá môže byś zodpovedná za zhoršenú vazodilatáciu. Zvýšená produkcia superoxidových radikálov v endoteli môže zvyšovaś inaktiváciu NO, a tým zapríeiniś zníženie jeho biologickej dostupnosti, eo môže viesś k zníženiu vazorelaxaených odpovedí cievnej steny. Na druhej strane, u SHR boli pozorované aj potlaeené, nezmenené, ale aj zvýšené relaxácie závislé od endotelu. Zdá sa, že diskrepancie v pozorovaných výsledkoch môžu spoeívaś v metodológii, v študovanom rieeisku a tiež vo veku experimentálnych zvierat.

A number of vascular diseases, including hypertension, are characterised by endothelial dysfunction caused by alterations in the production and action of the endothelium-derived relaxing (EDRFs) and/or endothelium-derived contracting (EDCFs) factors. The spontaneously hypertensive rat (SHR) is one of the most widely studied animal models for human essential hypertension. Several similarities between human primary hypertension and hypertension in the SHR have been pointed out in both the pathophysiology and the clinical course of the hypertensive disease. In human hypertension as well as in SHR, endothelium-dependent relaxation may be attenuated and this endothelial dysfunction contributes to the increased peripheral resistance. However, various results concerning endothelium-dependent relaxation, including impairment, no change and improvement have been reported in experimental hypertension. Endothelial dysfunction in hypertension has been linked to decrease in NO bioavailability, reflecting the impaired generation of NO and/or the enhanced inactivation of NO by reactive oxygen species. There is evidence that increased vascular oxidative stress is present in SHR. Thus, it has been proposed that oxidative inactivation of NO may account for the endothelial dysfunction seen in SHR. On the other hand, several studies demonstrate elevated basal NO synthesis in SHR rats which may be an adapting mechanism, preventing them from excessive blood pressure elevation. However, the role of NO in hypertension in SHR and in humans remains still controversial. We hypothesize that the vascular bed studied, the effect of age as well as methodological aspects, such as “precontraction” with different vasoconstrictors as well as antioxidants added to the solution for determination of the vasoreactivity may contribute to the discrepancies among studies. Nevertheless, the involvement of endothelial function in hypertension remains subject of debate and further research is needed to complete our knowledge on the role of NO, reactive oxygen species and other endothelial factors in the regulation of vascular and cardiac function.

• MeSH
• biologické markery MeSH
• cévní endotel fyziologie   patofyziologie   MeSH
• endoteliální buňky fyziologie   patologie   MeSH
• financování organizované MeSH
• hypertenze MeSH
• inbrední kmeny potkanů MeSH
• laboratorní zvířata MeSH
• modely nemocí na zvířatech MeSH
• oxid dusnatý krev   nedostatek   MeSH
• potkani Wistar MeSH
• signální transdukce MeSH
• vazodilatace MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• přehledy MeSH