Remodeling of intrinsic cardiac neurons: Effects of β-adrenergic receptor blockade in guinea pig models of chronic heart disease
Chronic heart disease induces remodeling of cardiac tissue and associated neuronal components. Treatment of chronic heart disease often involves pharmacological blockade of adrenergic receptors. This study examined the specific changes in neuronal sensitivity of guinea pig intrinsic cardiac neurons to autonomic modulators in animals with chronic cardiac disease, in the presence or absence of adrenergic blockage. Myocardial infarction (MI) was produced by ligature of the coronary artery and associated vein on the dorsal surface of the heart. Pressure overload (PO) was induced by a banding of the descending dorsal aorta (~20% constriction). Animals were allowed to recover for 2 wk and then implanted with an osmotic pump (Alzet) containing either timolol (2 mg·kg ·day ) or vehicle, for a total of 6-7 wk of drug treatment. At termination, intracellular recordings from individual neurons in whole mounts of the cardiac plexus were used to assess changes in physiological responses. Timolol treatment did not inhibit the increased sensitivity to norepinephrine seen in both MI and PO animals, but it did inhibit the stimulatory effects of angiotensin II on the norepinephrine-induced increases in neuronal excitability. Timolol treatment also inhibited the increase in synaptically evoked action potentials observed in PO animals with stimulation of fiber tract bundles. These results demonstrate that β-adrenergic blockade can inhibit specific aspects of remodeling within the intrinsic cardiac plexus. In addition, this effect was preferentially observed with active cardiac disease states, indicating that the β-receptors were more influential on remodeling during dynamic disease progression. © 2012 the American Physiological Society. -1 -1
American Journal of Physiology - Regulatory Integrative and Comparative Physiology
Hardwick, Jean C.; Marie Southerland, E.; Girasole, Allison E.; Ryan, Shannon E.; Negrotto, Sara; and Ardell, Jeffrey L., "Remodeling of intrinsic cardiac neurons: Effects of β-adrenergic receptor blockade in guinea pig models of chronic heart disease" (2012). Faculty Articles Indexed in Scopus. 1101.