Upregulation of AT1R and iNOS in the Rostral Ventrolateral Medulla (RVLM) Is Essential for the Sympathetic Hyperactivity and Hypertension in the 2K-1C Wistar Rat Model
Elizabeth Barbosa de Oliveira-Sales, Erika Emy Nishi, Mirian Aparecida Boim, Miriam Sterman Dolnikoff, Cássia T. Bergamaschi and Ruy R. Campos
Excess of angiotensin II (Ang II) plays an important role in the development and maintenance of two-kidney, one-clip (2K-1C) Goldblatt hypertension.
The purpose of the present study was to determine whether the upregulation of angiotensin type 1 receptor (AT1R) and inducible nitric oxide (NO) synthase (iNOS) within the rostral ventrolateral medulla (RVLM) could contribute to two-kidney, one-clip (2K-1C) hypertension.
Male wistar rats were divided into two as SHAM (control) and 2K-1C rat (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5450695/) based on the renal surgery.
The gene expression of iNOS as determined by the quantitative PCR and the protein expression of iNOS as determined western blotting in the RVLM were significantly higher in 2K-1C rats compared to SHAM rats. Also AT1R protein expression was increased in the RVLM of the 2K-1C rats when compared to SHAM rats.
Bilateral microinjection of losartan and aminoguanidine into the RVLM decreased the mean arterial pressure (MAP) and renal sympathetic nerve activity (rSNA) in the 2K-1C rats as compared with SHAM rats.
All these results suggest that Angiotensin II (via AT1R) and Nitric Oxide (produced by iNOS) in the RVLM are involved in the maintenance of arterial hypertension and sympathoexcitation in the 2K-1C rats.
Mahesh Kumar Sivasubramanian
Source: https://academic.oup.com/ajh/article/23/7/708/2281911