title: Angiotensin receptors alter myocardial infarction-induced remodeling of the guinea pig cardiac plexus.
abstract: Neurohumoral remodeling is fundamental to the evolution of heart disease. This study examined the effects of chronic treatment with an ACE inhibitor (captopril, 3 mg·kg(-1)·day(-1)), AT1 receptor antagonist (losartan, 3 mg·kg(-1)·day(-1)), or AT2 receptor agonist (CGP42112A, 0.14 mg·kg(-1)·day(-1)) 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 AT1 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 AT1 and AT2 receptors.
authors.affiliation: Department of Biology, Ithaca College, Ithaca, New York; jhardwick@ithaca.edu.
authors.forename: Jean C
authors.initials: JC
authors.lastname: Hardwick
authors.affiliation: Department of Biology, Ithaca College, Ithaca, New York;
authors.forename: Shannon E
authors.initials: SE
authors.lastname: Ryan
authors.affiliation: Department of Biology, Ithaca College, Ithaca, New York;
authors.forename: Emily N
authors.initials: EN
authors.lastname: Powers
authors.affiliation: Department of Biomedical Sciences, Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee;
authors.forename: E Marie
authors.initials: EM
authors.lastname: Southerland
authors.affiliation: University of California at Los Angeles (UCLA) Neurocardiology Research Center of Excellence, Los Angeles, California; and UCLA Cardiac Arrhythmia Center, Los Angeles, California.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Ardell
mesh_terms: D000200:Action Potentials; D000804:Angiotensin II / Q000494:pharmacology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D057912:Angiotensin II Type 2 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D004195:Disease Models, Animal; D004558:Electric Stimulation; D005071:Evoked Potentials; D006168:Guinea Pigs; D006321:Heart / Q000294:innervation*; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009638:Norepinephrine / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism*; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects / Q000378:metabolism*; D044139:Receptor, Angiotensin, Type 2 / Q000187:drug effects / Q000378:metabolism*; D017661:Receptors, Presynaptic / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D057912:Angiotensin II Type 2 Receptor Blockers; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D017661:Receptors, Presynaptic; D000804:Angiotensin II; D009638:Norepinephrine