BACKGROUND: Parasympathetic drive is attenuated in heart failure, and resulting autonomic imbalance may increase the risk of sudden cardiac death. The anatomic site(s) and molecular mechanisms underlying this parasympathetic withdrawal are unknown. METHODS AND RESULTS: We examined the effects of pre- and post-ganglionic vagal nerve stimulation (VS) and acetylcholine (ACh) application on the heart rate of rats with right-sided congestive heart failure (CHF) induced by monocrotaline. Heart rate reduction in response to pre-ganglionic VS in CHF rats in vivo was significantly less than in controls. The suppression of spontaneous beating of isolated right atria including the whole sinoatrial (SA) node in response to post-ganglionic VS was significantly attenuated in CHF rats as well. In contrast, ACh application to the right atria resulted in a significantly larger suppression of spontaneous beating in CHF rats than controls. Proteins of neuronal nitric oxide synthase (nNOS) in the right atria were significantly decreased, whereas muscarinic (M2) receptor was significantly increased in CHF rats compared with controls. CONCLUSIONS: Both pre-and post-ganglionic vagal nerve functions are diminished in CHF rats, whereas M2 receptor-mediated regulation of the SA node is upregulated. Downregulation of nNOS may be involved in this parasympathetic withdrawal.
BACKGROUND: Parasympathetic drive is attenuated in heart failure, and resulting autonomic imbalance may increase the risk of sudden cardiac death. The anatomic site(s) and molecular mechanisms underlying this parasympathetic withdrawal are unknown. METHODS AND RESULTS: We examined the effects of pre- and post-ganglionic vagal nerve stimulation (VS) and acetylcholine (ACh) application on the heart rate of rats with right-sided congestive heart failure (CHF) induced by monocrotaline. Heart rate reduction in response to pre-ganglionic VS in CHFrats in vivo was significantly less than in controls. The suppression of spontaneous beating of isolated right atria including the whole sinoatrial (SA) node in response to post-ganglionic VS was significantly attenuated in CHFrats as well. In contrast, ACh application to the right atria resulted in a significantly larger suppression of spontaneous beating in CHFrats than controls. Proteins of neuronal nitric oxide synthase (nNOS) in the right atria were significantly decreased, whereas muscarinic (M2) receptor was significantly increased in CHFrats compared with controls. CONCLUSIONS: Both pre-and post-ganglionic vagal nerve functions are diminished in CHFrats, whereas M2 receptor-mediated regulation of the SA node is upregulated. Downregulation of nNOS may be involved in this parasympathetic withdrawal.
Authors: Bruna C Brüler; Thayane C Vieira; Marcela Wolf; Stephany B Lucina; Fabiano Montiani-Ferreira; Marlos G Sousa Journal: Comp Med Date: 2018-04-02 Impact factor: 0.982