Abstract
Abstract Increased activity of the renin-angiotensin-aldosterone system (RAAS) plays a significant role in the development and progression of various cardio-metabolic diseases, such as hypertension, atherosclerosis and heart failure. Aliskiren is the newest antihypertensive drug and the first orally active direct renin inhibitor to become available for clinical use. This study investigated the acute and direct effects of Aliskiren on different parameters of oxidative stress on isolated rat heart. The hearts of male Wistar albino rats (n = 24, 8 per experimental group, age 8 weeks, body mass 180–200 g), were excised and retrogradely perfused according to the Langendorfftechnique at a gradually increasing perfusion pressure (40-120 cmH2O). Markers of oxidative stress (NO2 −, TBARS, H2O2 and O2 −) were measured spectrophotometrically after perfusion with three different concentrations of Aliskiren (0.1 μM, 1 μM, and 10 μM). The results demonstrated possible dose-dependent cardioprotective properties of Aliskiren, particularly with higher CPP. Lipid peroxidation (TBARS) levels decreased with the highest dose of Aliskiren and higher CPP, and the same trend was observed in nitrite (NO2 −) and hydrogen peroxide (H2O2) levels. These findings indicate that the acute effects of Aliskiren do not likely promote the production of reactive oxygen species upon higher pressure with the highest dose. Aliskiren may exert beneficial effects on oxidative stress biomarkers.
Highlights
Increased activity of the renin-angiotensin-aldosterone system (RAAS) plays a significant role in the development and progression of various cardiometabolic diseases, such as hypertension, atherosclerosis, diabetes and heart failure [1]
Blockade of RAAS, which plays a significant role in the development of essential hypertension, is suboptimal in combination with angiotensin II (AT II)-converting enzyme inhibitors (ACEIs) or ATII type 1 receptor blockers (ARB) [8]
NO2- release did not change significantly during the administration of 0.1 μM and 1 μM Aliskiren for any CPP valu ce compared with the control conditions
Summary
Increased activity of the renin-angiotensin-aldosterone system (RAAS) plays a significant role in the development and progression of various cardiometabolic diseases, such as hypertension, atherosclerosis, diabetes and heart failure [1]. Direct renin inhibitor blockade of RAAS at the rate-limiting step via reduction in plasma renin activity and levels of circulating angiotensin I and angiotensin II may be beneficial for cardiovascular risk in patients with essential hypertension and associated clinical conditions, such as diabetes and nephropathy [5, 6]. Aliskiren is the newest antihypertensive drug and the first orally active direct renin inhibitor (DRI) to become available for clinical use. Blockade of RAAS, which plays a significant role in the development of essential hypertension, is suboptimal in combination with angiotensin II (AT II)-converting enzyme inhibitors (ACEIs) or ATII type 1 receptor blockers (ARB) [8]. Several clinical trials confirmed the efficacy of Aliskiren on blood pressure reduction as a monotherapy [10, 11] and in combination therapy [12, 13]
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