Effects of chronic Beta blockade on disease‐induced remodeling in the guinea pig cardiac plexus

Chronic heart disease was surgically‐induced in guinea pigs. 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 weeks and then implanted with an osmotic pump (Alzet©) to deliver either 2mg/kg/day timolol or vehicle. Osmotic pumps were replaced after 3–4 weeks and treatment continued for another 3 weeks. At termination, intracellular recordings from individual intracardiac neurons in whole mounts of the cardiac plexus were used to assess changes in physiological responses. Timolol‐treatment inhibited the stimulatory effects of angiotensin II (Ang II) in control and PO animals, but not MI animals. Timolol treatment also inhibited the increase in synaptically‐evoked action potentials observed in PO animals with stimulation of fiber tract bundles. Analysis of phenotypic changes with immunohistochemistry demonstrated that timolol treatment did not alter the upregulation of neuronal nitric oxide synthase or cardiac mast cells seen with both cardiac disease states. These results demonstrate that beta adrenergic blockade can mitigate neurohumoral remodeling of the intrinsic cardiac associated with progression of cardiac disease. Supported by NIH HL098589 to JCH and EMS and HL71830 to JLA.