Arcuate Angiotensin II Increases Arterial Pressure via Coordinated Increases in Sympathetic Nerve Activity and Vasopressin Secretion

Abstract

Visual Abstract

Cell-specific transcriptome changes in the hypothalamic arcuate nucleus in a mouse deoxycorticosterone acetate-salt model of hypertension

“…The local RAS within the ARC is implicated in the integrated control of energy expenditure and may also contribute to blood pressure control ( Claflin et al, 2017 ; Shi et al, 2017 , 2021 , 2022 ; Morselli et al, 2018 ). Previous work demonstrates that DOCA-salt stimulates both energy expenditure and blood pressure through mechanisms that involve the brain RAS, and increasing evidence supports a major role for the ARC RAS in the integrated control of energy expenditure in response to various stimuli through the actions of AT 1 R within selected AgRP neurons ( Itaya et al, 1986 ; Kubo et al, 2000 ; Park and Leenen, 2001 ; Grobe et al, 2011 ; Claflin et al, 2017 ; Morselli et al, 2018 ; Oliveira et al, 2022 ).…”

Leptin Increases: Physiological Roles in the Control of Sympathetic Nerve Activity, Energy Balance, and the Hypothalamic–Pituitary–Thyroid Axis

“…Another hypothesized mechanism involves the actions of the renin-angiotensin system (RAS) in the brain, since the sympathoexcitatory and hypertensive actions of leptin require functional AngII type 1 receptors (AT1aR), whereas the anorexic effects apparently do not [24,146] (Figure 2). Similar to leptin and insulin, AngII in the ArcN increased SNA and blood pressure [158,159] in male rats through binding to AT1aR; the downstream pathway depended upon inhibition of NPY and stimulation of POMC neurons that project to the PVN [159]. A detailed neuroanatomical assessment of the location of AT1aR in the ArcN of male rats [159,160] revealed that (1) approximately 10% of AT1aR were expressed on NPY neurons; (2) AT1aR were rarely found on POMC neurons (4%); (3) instead, AT1aR were expressed largely in neurons that co-expressed both tyrosine hydroxylase (TyH; dopaminergic) and VGat2 (GABAergic) (see also ref.…”

“…Similar to leptin and insulin, AngII in the ArcN increased SNA and blood pressure [158,159] in male rats through binding to AT1aR; the downstream pathway depended upon inhibition of NPY and stimulation of POMC neurons that project to the PVN [159]. A detailed neuroanatomical assessment of the location of AT1aR in the ArcN of male rats [159,160] revealed that (1) approximately 10% of AT1aR were expressed on NPY neurons; (2) AT1aR were rarely found on POMC neurons (4%); (3) instead, AT1aR were expressed largely in neurons that co-expressed both tyrosine hydroxylase (TyH; dopaminergic) and VGat2 (GABAergic) (see also ref. [161]); (4) LepR positive neurons rarely co-expressed AT1aR.…”