Upregulation of β1, β2 and β3 adrenergic receptor expression in the hibernating bear myocardium: A role for cardioprotection?

Abstract

Hibernating grizzly bears demonstrate evidence of low sympathetic nervous system tone but may respond to noxious stimuli. We examined the ability of the hibernating bear to respond to catecholamine administration. Four bears were used to examine the effects of isoproterenol (ISO), on cardiac function during the active and hibernating period by echocardiography. Heart rate (HR), left ventricular (LV) ejection fraction (EF), diastolic filling volume (DV) and cardiac output index (CI) were measured. LV myocardium from 8 active, 8 hibernating bears were used to quantify β1, β2 and β3 AR mRNA expression by rtPCR. HR and LVEF were more sensitive to ISO during hibernation. HR increased by 47% (active) and 230% (hibernation). LVEF and CI were not different during the active period as DV was smaller with tachycardia. During hibernation, LV EF increased by 34% and CI increased by 238% while DV was maintained with tachycardia. Increased expression of β1, β2 and especially β3 ARs were found in hibernating bear LV myocardium. β2 AR activity is thought to be antiapoptotic and may contribute to myocardial protection during hibernation. β3 AR inhibits cardiac contraction and is thought to balance excess β1 stimulation (i.e., heart failure). Taken together, βAR regulation in hibernation may provide for a balanced heart rate, contractile and relaxation responsiveness (increasing CI) without sacrificing diastolic filling (myocardial perfusion).