Abstract 306: Alamandine but not angiotensin-(1-7) produces cardiovascular effects in the Insular Cortex
In the course of experiments aimed to evaluate the immunofluorescence distribution of MrgD receptors we observed the presence of immunoreactivity for the MrgD protein in the Insular Cortex. In order to evaluate the functional significance of this finding, we investigated the cardiovascular effects produced by the endogenous ligand of MrgD, alamandine, in this brain region. Urethane (1.4g/kg) anesthetized rats were instrumented for measurement of MAP, HR and renal sympathetic nerve activity (RSNA). Unilateral microinjection of alamandine (40 pmol/100nl), Angiotensin-(1-7) (40pmol/100nl), Mas/MrgD antagonista D-Pro7-Ang-1-7 (50pmol/100nl), Mas agonist A779 (100 pmol/100nl) or vehicle (0,9% NaCl) were made in different rats (N=4-6 per group) into posterior insular cortex (+1.5mm rostral to the bregma). Microinjection of alamandine in this region produced a long-lasting (> 18 min) increase in MAP (Δ saline= -2±1 vs. alamandine= 12±2 mmHg, p< 0.05) associated to increases in HR (Δ saline= 2±2 vs. alamandine= 35±5 bpm; p< 0.05) and in the amplitude of renal nerve discharges (Δ saline = -2±1 vs. alamandine= 35±5.5 % of the baseline; p< 0.05). Strikingly, an equimolar dose of angiotensin-(1-7) did not produce any change in MAP or HR (Δ MAP=-0.5±0.3 mmHg and +2.7±1.2 bpm, respectively; p> 0.05) and only a slight increase in RSNA (Δ =7.3±3.2 %) . In keeping with this observation the effects of alamandine were not significantly influenced by A-779 (Δ MAP=+13± 2.5 mmHg, Δ HR= +26±3.6 bpm; Δ RSNA = 25± 3.4%) but completely blocked by the Mas/MrgD antagonist D-Pro7-Ang-(1-7) (Δ MAP=+0 ± 1 mmHg Δ HR= +4±2.6 bpm; Δ RSNA = 0.5± 2.2 %). Therefore, we have identified a brain region in which alamandine/MrgD receptors but not Ang-(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 Ang-(1-7) in the brain.
Author Disclosures: F.R. Marins: None. A.C. Oliveira: None. F. Qadri: None. N. Alenina: None. M. Bader: None. M.A.P. Fontes: None. R.A.S. Santos: None.
- © 2014 by American Heart Association, Inc.