Decreased vagal control over heart rate in rats with right-sided congestive heart failure: downregulation of neuronal nitric oxide synthase.
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.


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.
Nihei
Motoki
M
Department of Circulation and Humoral Regulation, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan.
Lee
Jong-Kook
JK
Honjo
Haruo
H
Yasui
Kenji
K
Uzzaman
Mahmud
M
Kamiya
Kaichiro
K
Opthof
Tobias
T
Kodama
Itsuo
I
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D016280:Atrial Function, Right; D015536:Down-Regulation; D006325:Heart Atria / Q000737:chemistry / Q000201:enzymology; D006333:Heart Failure / Q000139:chemically induced / Q000503:physiopathology*; D006339:Heart Rate / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D016686:Monocrotaline / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D052248:Nitric Oxide Synthase Type I; D051381:Rats; D017208:Rats, Wistar; D043585:Receptor, Muscarinic M2 / Q000032:analysis / Q000502:physiology; D012849:Sinoatrial Node; D014630:Vagus Nerve / Q000502:physiology*
D009419:Nerve Tissue Proteins; D043585:Receptor, Muscarinic M2; D016686:Monocrotaline; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D000109:Acetylcholine