Downregulation of AT1 receptor in the RVLM induced by mesenchymal stem cells treatment prevent the hypertension and sympathetic hyperactivity in 2K‐1C Wistar rats

Abstract

Current approaches to pharmacological treatment of renovascular hypertension are problematic and thus, alternative therapies are needed. We investigated the effects of mesenchymal stem cells (MSC) treatment on systolic arterial pressure (SAP), renal sympathetic nervous activity (rSNA) and AT1 receptor (AT1R) expression in the rostral ventrolateral medulla (RVLM) in an experimental model of renovascular hypertension, 2 Kidney‐1 clip (2K‐1C). Fluorescently tagged MSC (2×105cells/animal, IV) were injected weekly after the 3rd week of renal artery occlusion and the experiments were performed at the end of 6 weeks after clipping. The rats were divided in control group (n=5), control group treated with MSC (n=2), 2K‐1C (n=8) and 2K‐1C treated (n=7). Bilateral punches were taken from the RVLM to perform AT1R protein expression analyses by western blotting. Tracking assays by citometry showed MSC in the medulla oblongata. SAP in 2K‐1C‐treated rats was lower compared to untreated animals (2K‐1C, 224 ± 8 vs 173 ± 6 mmHg, p<0,05) at 6th week followed by a significant decrease in rSNA (27%). MSC treatment reduced brainstem AT1R expression only 2K‐1C rats (28%, p<0,05). Therefore, the results suggest MCS treatment can both prevent the increase in SAP as well as reduce the sympathetic hyperactivity and the expression of AT1R in the RVLM, constituting a future alternative for the treatment of this type of hypertension.Supported by CAPES