Contrasting effects of propranolol on sympathetic nerve activity and vascular resistance during orthostatic stress.
BACKGROUND
Previous studies in humans advanced the concept that cardiac filling pressure and contractility, the primary determinants of ventricular mechanoreceptor discharge, are important determinants of sympathetic outflow during orthostatic stress. Thus, intravenous propranolol greatly attenuated forearm vasoconstrictor response to venous pooling with lower body negative pressure (LBNP). The aim of this study was to reevaluate the experimental support for this concept by using direct measurements of sympathetic nerve activity.


RESULTS
In 11 healthy humans, we recorded muscle sympathetic nerve activity (MSNA) with microelectrodes (peroneal nerve), as well as blood flow in the forearm and calf (venous occlusion plethysmography) at baseline and during graded LBNP. The same experiments were repeated after administration of propranolol (0.15 mg/kg i.v.), which is thought to decrease ventricular mechanoreceptor discharge. The major new findings are that propranolol neither increased baseline MSNA nor attenuated the increases in MSNA during graded orthostatic stress even though in the same subjects, propranolol simultaneously increased the baseline level of vascular resistance in both the forearm and calf and substantially attenuated the increases in regional vascular resistance during orthostatic stress.


CONCLUSIONS
Systemic beta-blockade causes a marked dissociation between sympathetic outflow and vascular resistance that invalidates the use of intravenous propranolol as an experimental model to examine the reflex effects of ventricular mechanoreceptors on peripheral vascular resistance in humans.
Jacobsen
T N
TN
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75235-9034.
Converse
R L
RL
Victor
R G
RG
D000328:Adult; D006321:Heart / Q000294:innervation*; D006801:Humans; D007024:Hypotension, Orthostatic / Q000503:physiopathology*; D008150:Lower Body Negative Pressure; D008297:Male; D008465:Mechanoreceptors / Q000187:drug effects* / Q000502:physiology; D009132:Muscles / Q000294:innervation; D011433:Propranolol / Q000494:pharmacology*; D015203:Reproducibility of Results; D013564:Sympathetic Nervous System / Q000187:drug effects*; D014655:Vascular Resistance / Q000187:drug effects*
D011433:Propranolol