Chemogenetic activation of intracardiac cholinergic neurons improves cardiac function in pressure overload induced heart failure.

This study tests if ICG cholinergic neuron activation mitigates the progression of cardiac dysfunction and reduces mortality that occurs in HF. HF was induced by transaortic constriction (TAC) in male transgenic Long Evans rats expressing Cre recombinase within choline acetyltransferase (ChAT) neurons. ChAT neurons were selectively activated by expression and activation of excitatory Designer Receptors Exclusively Activated by Designer Receptors (DREADDs) by Clozapine-N-Oxide (TAC +Treatment & Sham Treated groups). Control animals expressed DREADDs but received saline (Sham and TAC groups). A separate set of animals were telemetry instrumented to record blood pressure (BP) and heart rate (HR). Acute activation of ICG neurons resulted in robust reductions in BP (~20 mmHg) and HR (~100 bpm). All groups of animals were subjected to weekly echocardiography and treadmill stress tests from 3-6 weeks post TAC/Sham surgery. Activation of ICG cholinergic neurons reduced the left ventricular systolic dysfunction (reductions in ejection fraction, fractional shortening, stroke volume and cardiac output) and cardiac autonomic dysfunction (reduced HR recovery (HRR) post peak effort) observed in TAC animals. Additionally, activation of ICG ChAT neurons reduced mortality by 30% compared to untreated TAC animals. These data suggest that ICG cholinergic neuron activation reduces cardiac dysfunction and improves survival in HF, indicating ICG neuron activation could be a novel target for tr...
Source: American Journal of Physiology. Heart and Circulatory Physiology - Category: Physiology Authors: Tags: Am J Physiol Heart Circ Physiol Source Type: research