Angiotensin II AT1 receptor alters ACE2 activity, eNOS expression and CD44-hyaluronan interaction in rats with hypertension and myocardial fibrosis

Clinical Implications of SARS-CoV-2 Interaction With Renin Angiotensin System

“…However, rats treated with telmisartan exhibited significantly increased ACE2 activity and eNOS expression in intracardiac vessels and intermyocardium as well as downregulated local expression of AT1 receptor. Treatment with telmisartan also inhibited membrane CD44 expression and reduced TGFβ and Smad expression [46]. Studies in normotensive rats with post coronary artery ligation left ventricular remodeling and dysfunction, exhibited partial resolution following losartan and olmesartan treatment while augmenting plasma concentrations of the angiotensins [47].…”

“…The possibility that the effects of olmesartan on vascular ACE2 gene and protein expression were the result of reduced arterial blood pressure was ruled out given the comparative effect observed in mice treated with atenolol or hydralazine [45]. Sprague-Dawley rats treated on a 4-week course of Ang II infusion showed Ang II upregulated AT1 receptor, downregulated AT2 receptor, ACE2 activity, eNOS expression and increased CD44 expression and hyaluronidase [46]. However, rats treated with telmisartan exhibited significantly increased ACE2 activity and eNOS expression in intracardiac vessels and intermyocardium as well as downregulated local expression of AT1 receptor.…”

“…Regardless of how SARS-CoV2 completes virion assembly, it is clear that membranebound ACE2 would play a physiological role in the replication of the novel virus. The question remains whether the use of ACE inhibitors, ARBs, and MRAs should be avoided in the setting of SARS-CoV infection given each agent [43][44][45][46][47]54] upregulates ACE2 expression and activity.…”

Treatment with dietary cyclosporine has no direct effect on myocardial fibrosis and hypertension in mice

“…Total proteins (60 μg) were extracted, fractionated by 10% SDS-polyacrylamide gel electrophoresis, and transferred to polyvinylidene difluoride membrane as described previously. 9 The membrane was then incubated at 4˚C overnight with the following antibodies: a rabbit anti-ACE2 polyclonal antibody (1:800), rabbit anti-AT1 (1:800) and AT2 (1:400) receptor polyclonal antibodies (Santa Cruz Biotech, Dallas, TX, USA), a rabbit anti-MCP-1 polyclonal antibody and a mouse monoclonal anti-TGFβ1 antibody (1:1000, Abcam, Inc. MA, USA), and mouse anti-collagen type I and III monoclonal antibodies (1:5000, Sigma Chemical Co., MO, USA), respectively. Bound antibody was detected by horseradish peroxidase-conjugated anti-mouse IgG.…”

“…The paraffin-embedded tissue sections (4μm thick) were dewaxed in xylene, and rehydrated through graded alcohols as previously reported. 9 Briefly, the sections were incubated overnight with primary antibodies including a mouse monoclonal antibody against macrophages (1:200, Millipore, CA, USA) and a monoclonal antibody against α-smooth muscle actin (SMA, 1:800, Sigma Chemical Co., MO, USA), respectively. The slides were incubated with a biotinylated horse anti-rabbit IgG or an anti-mouse IgG (Vector Laboratories), stained using the ABC-peroxidase kit or ABC-AP (Alkaline phosphatase, Vector Laboratories, CA, USA) and visualized with 3,3'-diaminobenzidine tetrahydrochloride or alkaline phosphatase substrate kit (Sigma, MO, USA).…”