Central muscarinic receptors play an important role in the regulation of ca
rdiac vagal nerve activity. We studied the inhibition of central muscarinic
receptors and sympathetic nerve function in humans, since very little info
rmation is currently available on this subject. We examined the effects of
graded doses of atropine (five doses, range 0.001 to 0.016 mg/kg) on heart
rate, arterial pressure, heart rate variability, and muscle sympathetic ner
ve activity in 13 healthy young volunteers. Atropine caused biphasic effect
s on heart rate and the high-frequency (HF) power of R-R interval variabili
ty. At lower doses (less than or equal to 0.002 mg/kg for heart rate, 0.001
mg/kg for HF power), atropine decreased heart rate and increased HF power.
In contrast, at higher doses, atropine increased heart rate and decreased
HF power. Low-dose atropine significantly attenuated muscle sympathetic ner
ve activity, burst rate (bursts/min) by -30.5 +/- 6.0% and burst incidence
(bursts/100 heart beats) by -23.8 +/- 6.9% at 0.002 mg/kg, Systolic and dia
stolic arterial pressure did not change with atropine infusion. Low-dose at
ropine (less than or equal to 0.002 mg/kg) did not significantly affect eit
her low frequency (LF) power or LF/HF. These results suggest that central m
uscarinic receptors may modulate not only cardiac vagal nerve activity but
also sympathetic nerve activity in the skeletal muscle vasculature.