Angiotensin receptors alter myocardial infarction-induced remodeling of the guinea pig cardiac plexus

Abstract

), or AT2 receptor agonist (CGP42112A, 0.14 mg·kg Ϫ1 ·day Ϫ1 ) on remodeling of the guinea pig intrinsic cardiac plexus following chronic myocardial infarction (MI). MI was surgically induced and animals recovered for 6 or 7 wk, with or without drug treatment. Intracellular voltage recordings from whole mounts of the cardiac plexus were used to monitor changes in neuronal responses to norepinephrine (NE), muscarinic agonists (bethanechol), or ANG II. MI produced an increase in neuronal excitability with NE and a loss of sensitivity to ANG II. MI animals treated with captopril exhibited increased neuronal excitability with NE application, while MI animals treated with CGP42112A did not. Losartan treatment of MI animals did not alter excitability with NE compared with untreated MIs, but these animals did show an enhanced synaptic efficacy. This effect on synaptic function was likely due to presynaptic AT1 receptors, since ANG II was able to reduce output to nerve fiber stimulation in control animals, and this effect was prevented by inclusion of losartan in the bath solution. Analysis of AT receptor expression by Western blot showed a decrease in both AT 1 and AT2 receptors with MI that was reversed by all three drug treatments. These data indicate that neuronal remodeling of the guinea pig cardiac plexus following MI is mediated, in part, by activation of both AT 1 and AT2 receptors.

Translational neurocardiology: preclinical models and cardioneural integrative aspects

“…; Hardwick et al . ). The intrinsic cardiac nervous system is the cornerstone of cardiocentric reflexes; that is, reflexes that are confined to the periphery and with the heart as their target organ.…”

“…Being involved in inter-ganglionic interactions, the local circuit neurons subserve critical roles in integrated control of cardiac function among peripheral ganglia and between peripheral and central components of the cardiac nervous system. These local circuit neurons may serve as the primary targets for pharmacological and/or bioelectric therapeutic strategies to mitigate the hyperdynamic cardiac reflex responses accompanying progression of cardiac disease (Armour, 2008;Gibbons et al 2012;Beaumont et al 2015;Hardwick et al 2015). The intrinsic cardiac nervous system is the cornerstone of cardiocentric reflexes; that is, reflexes that are confined to the periphery and with the heart as their target organ.…”

Angiotensin peptide synthesis and cyclic nucleotide modulation in sympathetic stellate ganglia

“…Angiotensin II (AngII) is a major effector of the Renin-Angiotensin system (RAS) that mediates its effects in a wide range of organs [2][3][4] via selective activation of AngII receptors type 1 and 2 (AT 1 R, AT 2 R) [5,6]. Altered RAS signaling is evident in hypertension [7][8][9][10][11], heart failure [12][13][14] and post-myocardial infarction [15][16][17][18], where AngII-AT 1 R activation is involved in enhanced sympathetic transmission [19][20][21], cardiac hypertrophy [8,13,[22][23][24] impaired calcium handling [9], vascular remodeling [3,4] and pro-inflammatory events [25,26] that all contribute to cardiac arrhythmia [27].…”

Autonomic nervous system and cardiac neuro-signaling pathway modulation in cardiovascular disorders and Alzheimer’s disease

“…Hardwick and colleagues have studied the implications of the ACE inhibitor captopril on cardiac plexus remodeling triggered during MI in a guinea pig model ( Hardwick et al, 2015 ). Notably, they tested the involvement of AT1 receptor antagonists, such as losartan, together with AT2 receptor stimulation.…”