Nitric oxide synthases in vagal neurons are crucial for the regulation of heart rate in awake dogs.
Nitric oxide synthase (NOS) inhibitors elicit bradycardias independent of the endothelium (e-NOS) or increases in blood pressure. Therefore, this bradycardia could be mediated by other NOS isoforms, most likely that of the nervous system (n-NOS). If so, heart rate variability (HRV) as a measure of vagal activity should be an indicator of the activity of n-NOS in vagal neurons. To test this, we studied the dose-effect relations of L-NAME (0.3 - 50 mg x kg(-1)) on heart rate (HR), HRV and systemic vascular resistance (SVR) in seven awake dogs. HRV was analyzed in the time domain as standard deviation of the RR-intervals (SDNN) and in the frequency domain as power in the high (0.15 - 0.5 Hz) and low (0.04 - 0.15 Hz) frequency range. The effects of HR and SDNN reached their maxima at a dose of 3 mg x kg(-1) and had their ED50 at 0.27 +/- 0.03 mg x kg(-1) and 0.43 +/- 0.1 mg x kg(-1), respectively, whereas SVR had its maximum at 10 mg x kg(-1) and ED50 at 0.86 +/- 0.11 mg x kg(-1) (p < 0.05). HF-power (vagal activity) predominated compared to LF-power (mainly sympathetic activity) during baseline as well as after L-NAME. The effects on HR and HRV were absent after ganglionic blockade (hexamethonium), whereas the effects on SVR remained unchanged. Thus, NO exerts a powerful restraining activity on vagal neurons and plays a key role in the adjustment of heart rate in awake resting animals with prevailing vagal activity.
Picker
O
O
Department of Experimental Anesthesiology, Heinrich-Heine University, Düsseldorf, Germany. olaf.picker@uni-duesseldorf.de
Scheeren
T W
TW
Arndt
J O
JO
D000818:Animals; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005730:Ganglionic Blockers / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology*; D018738:Hexamethonium / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009474:Neurons / Q000201:enzymology*; D019001:Nitric Oxide Synthase / Q000502:physiology*; D052248:Nitric Oxide Synthase Type I; D014630:Vagus Nerve / Q000166:cytology / Q000201:enzymology*; D014655:Vascular Resistance / Q000187:drug effects
D004791:Enzyme Inhibitors; D005730:Ganglionic Blockers; D018738:Hexamethonium; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D019331:NG-Nitroarginine Methyl Ester