The Role of Angiotensin II in Experimental Acute Kidney Injury and Cardiorenal Failure

Abstract: Blood pressure and fluid regulation are kept constant through the interaction between heart and kidneys. When the systemic blood pressure decreases, the levels of the hormone Angiotensin II increase, leading to vasoconstriction and therefore increased blood pressure. Angiotensin II may act directly on the vessels or cause fluid retention in the kidneys, consequently increasing blood pressure. Dysfunctional heart and kidneys lead to different diseases, such as heart failure and acute kidney injury. A failing heart can cause damage to kidneys and vice versa, leading to cardiorenal syndrome. Due to the severity of these diseases and their increasing prevalence, it is important to investigate them further. Therefore, the aim of this thesis was to evaluate blockage or treatment of Angiotensin II on the effects on renal and cardiac function.Study I investigates the effect of Losartan, an Angiotensin receptor blocker, on kidney oxygenation as well as the effect on blood pressure, after resuscitated haemorrhage and Norepinephrine administration. It showed that Losartan does not worsen the effects of kidney oxygenation. The blood pressure managing affects of Norepinephrine were also not worsened in rats treated with Losartan.Study II-IV investigate treatment of Angiotensin II and high salt diet on renal and cardiac function in Balb/CJ and C57BL/6J mice. This treatment showed increased mortality in Balb/CJ mice compared to C57BL/6J. Balb/CJ also retained more fluid and sodium than C57BL/6J and had worsened cardiac function after Angiotensin II and salt treatment. These are signs of heart failure and decompensation. Balb/CJ had lower amount of oxidative stress, compared to C57BL/6J. Treating the latter with the antioxidant N-acetylcysteine, reduced the levels of oxidative stress, but increased the mortality.In conclusion, Angiotensin II treatment or blockage has different effects on both renal function as well as cardiac function, depending on strain and treatment settings.