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.

Ústav normálnej a patologickej fyziológie SAV Centrum excelentnosti pre kardiovaskulárny výskum Bratislava

Endothelial (dys)function in the experimental model of primary hypertension

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