The effects of acute administration of losartan, Angiotensin II type-1 receptor antagonist, on hemodynamics and oxidative stress parameters in malignant hypertensive rats

Abstract

Malignant hypertension is a severe form of hypertension which pathogenesis is not fully elucidated. The aim of our study was to investigate the role of Angiotensin II on hemodynamic and oxidative stress parameters in model of malignant hypertension by using losartan. Adult males were divided into three groups: normotensive Wister rats, control SHR and losartan treated SHR. Control and SHR group received a single bolus dosage of saline, while the SHR + LOS group received a losartan. Blood pressure, cardiac output, both total peripheral and carotid vascular resistance and carotid blood flow were measured. CAT, SOD and TBARS were determined in the blood samples. The treatment significantly decreased the blood pressure. There was no significant change in cardiac output or carotid blood flow, but treatment resulted in diminishment of vascular resistances, both total peripheral and carotid. There was a tendency to restore the values of SOD activity towards those of the normotensive group, but there were no change in CAT and TBARS levels. Taken together, our results show that a single application of losartan has a strong hypotensive effect. Angiotensin II seems to have a significant role in the malignant hypertension syndrome and it partially affects oxidative stress parameters.

Maligna hipertenzija predstavlja posebno težak oblik hipertenzije čija patogeneza nije u potpunosti razjašnjena. Cilj naše studije bio je ispitivanje uloge Angiotenzina II (Ang II) u regulaciji hemodinamskih i parametara oksidativnog stresa u modelu maligne hipertenzije. Mužjaci odraslih pacova su podeljeni u tri grupe: normotenzivne Wistar pacove, kontrolne hipertenzivne (SHR) i losartanom tretirane hipertenzivne pacove (SHR+LOS). Kontrolna i SHR grupa su primile po jednu bolus dozu fiziološkog rastvora, dok je SHR+LOS grupa primila losartan, receptorni blokator Ang II, Nakon toga su mereni krvni pritisak, minutni volumen srca (MV), karotidni protok krvi (KPK) i određivani odgovarajući otpori: ukupni periferni otpor (UPO) i karotidni vaskularni otpor (KVO). Parametri oksidativnog stresa: aktivnost katalaze (CAT), aktivnost superoksid dismutaze (SOD) i marker lipidne peroksidacije (TBARS) su određivani iz uzoraka krvi. Tretman losartanom je značajno snizio vrednost krvnog pritiska. Nije došlo do značajnih promena vrednosti MV ni KPK, ali je tretman losartanom doveo do smanjenja UPO i KVO. U ovoj grupi je uočena tendencija povećanja aktivnosti SOD ka vrednostima normotenzivnih životinja, ali nije bilo promena u vrednostima CAT i TBARS. Naši rezultati pokazuju da jednokratna aplikacija losartana ima snažan hipotenzivni efekat i da Ang II igra značajnu ulogu u mehanizmima maligne hipertenzije, delimično preko antioksidativnog delovanja. PR Projekat Ministarstva nauke Republike Srbije, br. OI 175096.