Abstract 197: Selective Destruction of Adrenergic Cells in Mice Leads to Severe Left-ventricular Dysfunction at Rest With Apparent Stress-induced Recovery
The catecholamines epinephrine and norepinephrine play critical roles in the maintenance of cardiovascular function. Phenylethanolamine-N-methyltransferase (Pnmt) catalyzes the conversion of norepinephrine to epinephrine and serves as a marker for adrenergic cells. We have previously shown that the selective destruction of Pnmt+ cells in the mouse produces severe left-ventricular dysfunction under anesthesia and that epinephrine deficiency alone does not recapitulate the phenotype. Here, we test the hypothesis that Pnmt+ cells are key modulators of the stress response to immobilization. Using a suicide reporter mouse model to ablate Pnmt+ cells (Pnmt-Cre/DTA), we achieve greater than 50% Pnmt+ cell reduction in the adrenal medulla and 97% reduction in Pnmt transcript. Remarkably, Pnmt+ cell destruction does not markedly diminish the cardiovascular response to restraint stress. At one hour of immobilization, heart rate and ejection fraction showed a similar increase in response to restraint in both groups, despite apparent heart failure in Pnmt-Cre/DTA mice at rest (Figure 1). Here, we show that, while Pnmt+ cells are required for the maintenance of basal cardiovascular function, loss of these cells does not diminish the cardiovascular response to restraint stress. These results suggest that left ventricular cardiac muscle has the capacity to respond to stress despite hypokinetic and poor ventricular function at baseline.
Author Disclosures: A.P. Owji: None. C.N. Baker: None. J. Jacob: None. S.N. Ebert: None.
- © 2015 by American Heart Association, Inc.