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Alamandine but not angiotensin-(1-7) produces cardiovascular effects at the rostral insular cortex

Item Type:Article
Title:Alamandine but not angiotensin-(1-7) produces cardiovascular effects at the rostral insular cortex
Creators Name:Marins, F.R., Oliveira, A.C., Qadri, F., Motta-Santos, D., Alenina, N., Bader, M., Fontes, M.A.P. and Souza Santos, R.
Abstract:Experiments aimed to evaluate the tissue distribution of Mas-related G-protein coupled receptor D (MrgD) revealed the presence of immunoreactivity for the MrgD protein in the rostral insular cortex (rIC), an important area for autonomic and cardiovascular control. In order to investigate the relevance of this finding, we evaluated the cardiovascular effects produced by the endogenous ligand of MrgD, alamandine, in this brain region. Mean arterial pressure (MAP), heart rate (HR) and renal sympathetic nerve activity (RSNA) were recorded in urethane anesthetized rats. Unilateral microinjection of equimolar doses of alamandine (40pmol/100nl), angiotensin-(1-7), angiotensin II, angiotensin A and Mas/MrgD antagonist D-Pro(7)-Ang-1-7 (50pmol/100nl), Mas antagonist A779 (100pmol/100nl) or vehicle (0.9% NaCl) were made in different rats (N=4-6 per group) into rIC. To verify the specificity of the region, a microinjection of alamandine was also performed into intermediate insular cortex (iIC). Microinjection of alamandine in rIC produced an increase in MAP (Δ=15±2mmHg), HR (Δ=36±4bpm) and RSNA (Δ=31±4%), but was without effects at iIC. Strikingly, an equimolar dose of angiotensin-(1-7) at rIC did not produce any change in MAP, HR and RSNA. Angiotensin II and angiotensin A produced only minor effects. Alamandine effects were not altered by A-779, a Mas antagonist, but were completely blocked by the Mas/MrgD antagonist D-Pro(7)-Ang-(1-7). Therefore, we have identified a brain region in which alamandine/MrgD receptor but not angiotensin-(1-7)/Mas could be involved in the modulation of cardiovascular-related neuronal activity. This observation also suggests that alamandine might possess unique effects unrelated to angiotensin-(1-7) in the brain.
Keywords:Alamandine, Angiotensin-(1-7), Insular Cortex, Cardiovascular, Animals, Rats
Source:American Journal of Physiology Regulatory Integrative and Comparative Physiology
ISSN:0363-6119
Publisher:American Physiological Society
Volume:321
Number:3
Page Range:R513-R521
Date:10 September 2021
Official Publication:https://doi.org/10.1152/ajpregu.00308.2020
PubMed:View item in PubMed

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