Reversion of cardiovascular remodelling in renovascular hypertensive 2K‐1C rats by renin–angiotensin system inhibitors

Abstract

Objectives Evaluate whether the RAS dual blockade would induce additional beneficial effects on cardiovascular remodelling when compared to monotherapy in renal hypertensive two kidneys–one clip (2K‐1C) rats. Methods Hypertensive 2K‐1C and normotensive (2K) rats were treated for 14 days with submaximal doses of losartan (LOS), enalapril (ENA), losartan plus enalapril (LOS + ENA) or vehicle (water). Blood pressure and some parameters of cardiovascular remodelling were evaluated. Results Systolic blood pressure (SBP) was higher in 2K‐1C (209 ± 3 mm Hg, P < .05) than in 2K (113 ± 1 mm Hg) rats. There was an additional effect in 2K‐1C treated with LOS + ENA (153 ± 9 mm Hg) on lowering SBP when compared to LOS (184 ± 12 mm Hg) or ENA (177 ± 9 mm Hg). None of the treatments had effect on SBP in 2K rats. In 2K‐1C, cardiomyocyte hypertrophy was reduced by all treatments, although the cardiac hypertrophy indexes remained unchanged. 2K‐1C aortas presented medial thickening that was partially reduced by the treatments. Intimal hyperplasia observed in 2K‐1C (15.56 ± 0.89 µm vs 8.24 ± 0.80 µm) was reversed by ENA (9.52 ± 0.45 µm) or LOS + ENA (8.17 ± 0.53 µm). Collagen deposition was increased in 2K‐1C hearts (1.77 ± 0.16 vs 1.28 ± 0.09) and aortas (8.1 ± 0.6 vs 5.2 ± 0.2). Treatment with LOS reduced (1.12 ± 0.14%) and ENA (0.81 ± 0.11%) or LOS + ENA (0.86 ± 0.11%) additionally diminished collagen only in 2K‐1C hearts. Conclusions Submaximal doses of ACEi and/or ARB have inhibitory actions on cardiac remodelling and vascular hypertrophy not entirely dependent on their effects on blood pressure normalization in renovascular hypertensive rats. Combined therapy produced additional reduction in blood pressure than monotherapy despite a similar inhibition on cardiovascular remodelling.

Comparative analysis of hypertensive nephrosclerosis in animal models of hypertension and its relevance to human pathology. Glomerulopathy

“…There were no differences between control and hypertensive animals in body and kidney weights. As previously reported, all models developed stable hypertension and mild impairment in renal function [ 14 , 64 , 66 , 67 ] ( Table 3 ).…”

“…At the end of the experiment, the animals were weighed and killed after anesthesia with tribromoethanol (50 mg/kg i.p.). The body and kidney weight, tibia length, glomerular filtration rate were measured and analysed as described [ 67 ].…”

“…The kidney tissues from these previously published studies [ 14 , 64 , 66 , 67 ] were used for current histopathologic analysis. Kidneys were fixed in in 10% neutral buffered zinc-formalin and embedded in paraffin.…”

Clitoria ternatea (Linn.) flower extract attenuates vascular dysfunction and cardiac hypertrophy via modulation of Ang II/AT1R/TGF‐β1 cascade in hypertensive rats

“…Furthermore, several molecular mechanisms contribute to the pathogenesis of cardiac hypertrophy. Many studies have shown LV hypertrophy in 2K‐1C rats that was associated with elevated blood pressure and RAS activation 41,42 . Inhibition of Ang II generation using ACE inhibitors was shown to reverse cardiac remodelling in 2K‐1C hypertensive rats 41 .…”

Antiproteinuric and Hyperkalemic Mechanisms Activated by Dual Versus Single Blockade of the RAS in Renovascular Hypertensive Rats

“…The animals were housed at the Heart Institute animal facility under a constant temperature and a 12:12-h dark-light cycle and had free access to food and water. The two-kidney one-clip (2K-1C) renovascular-hypertension was induced as described previously ( Corrêa et al, 2020 ). Briefly, rats were anesthetized with tribromoethanol (50 mg/kg i.p.)…”