Uloga angiotenzina II i reaktivnih vrsta kiseonika tokom razvoja akutne bubrežne insuficijencije u eksperimentalnoj hipertenziji

Abstract

Akutna bubrežna insuficijencija (ABI) se definiše kao nagli gubitak bubrežne funkcije. Uzroci nastanka ABI su mnogobrojni, a mehanizmi razvoja još uvek nedovoljno jasni. Karakterišu je iznenadna pojava, brzi tok, neizvesna i često loša prognoza krajnjeg ishoda bolesti. ABI je česta pojava kod hospitalizovanih pacijenata, a učestalost njenog nastanka na odeljenjima intenzivne nege se kreće do 30%. Udružena sa drugim oboljenjima, poput hipertenzije, uzrokuje visok stepen mortaliteta. Savremena istraživanja pokazuju da hipertenzija i oksidativni stres imaju važnu ulogu u progresiji bubrežnih oboljenja, što je usmerilo i stavilo akcenat naših istraživanja na uloge ova dva patogenetska faktora u nastanku i progresiji ABI. Sistem renin angiotenzin aldosteron (RAAS) ima značajnu ulogu u održanju krvnog pritiska i homeostatskih mehanizama bubrega. On u velikoj meri reguliše bubrežnu hemodinamiku i vaskularnu reaktivnost, a kako je intrarenalna vazokonstrikcija jedan od glavnih mehanizama razvoja ABI, očita je njegova uloga u patogenetskim mehanizmima nastanka ove bolesti. Oksidativni stres predstavlja disbalans između produkcije reaktivnih vrsta kiseonika (RVK) i sposobnosti biološkog sistema da ih uklanja ili da reparira oštećenja nastala produkcijom ovih molekula. Reaktivne vrste kiseonika su izuzetno reaktivne supstance usled postojanja nesparenih elektrona, i kao takve mogu da uzrokuju oštećenja na DNK, RNK, kao i nekim proteinima koji imaju ulogu u procesu starenja. Pokazano je da oksidativni stres ima veliku ulogu u razvoju mnogih oboljenja, kao što su Alchajmerova i Parkinsonova bolest, i neki kardiovaskularni poremećaji. Takodje je dokazano da, prilikom ishemičnih povreda organa i tkiva, nakon hipoksije, a tokom reperfuzije, dolazi do povećane produkcije molekula RVK. Iz pomenutih razloga, sasvim je izvesno da u ishemičnoj formi ABI povećana koncentracija ovih molekula, doprinosi nastanku i razvoju ovog teškog oboljenja...

Acute renal failure (ARF) is defined as a sudden loss of renal function. It’s multifactorially caused, but the mechanism of pathogenesis and developement of this disease is still uncomplitely defined. ARF is characterized by sudden appearance, rapid progression of disease and very uncertain and often fatal outcome. ARF frequently occurres with hospitalized patients. The frequency of its occurrence in the intensive care units moves up to 30%. Associated with other diseases, such as hypertension, it causes high rate mortality. Recent studies show that hypertension and oxidative stress have an important role in the renal disease progression. This fact directed the focus of our study towards the influence of these two pathogenetic factors in development and progression of ARF. The system rennin angiotensin aldosterone (RAAS) has a great role in blood pressure control and kidney homeostatic mechanisms. It mostly regulates the renal hemodynamic, but considering the fact that the intrarenal vasoconstriction is one of the major mechanisms of ARF development, it obviously influences the pathogenetic mechanisms in the development of this disorders. Oxidative stress is defined as a disbalance between the production of reactive oxygen species (ROS) and an ability of biological system to remove or fix the damage made due to production of these molecules. Reactive oxygen species are highly reactive due to presence of unpaired electrons and consequently lead to damage of DNA, RNA and some other ageing related proteins. There is evidence that the oxidative stress has a great influence in the progression of numerous diseases, such as Alzheimer’s, Parkinson’s, as well as some cardiovascular disorders. Furthermore, during the ischemia/reperfusion injuries of organs and tissues, there is increased reactive oxygen species molecule production. Thus, the ischemic type of ARF is characterized by a high concentration of these molecules which contribute to the development of this devastating illnes...