From the Autonomic Dysfunction Center, Vanderbilt University, Nashville,
Tenn.
Correspondence to David Robertson, MD, Autonomic Dysfunction Center, AA3228 MCN, Vanderbilt University, Nashville, TN 37232-2195. E-mail david.robertson{at}mcmail.vanderbilt.edu
Abstract—Systemic administration of
adrenergic agonists and nitric oxide donors is used extensively to
determine cardiovascular receptor sensitivity.
Conclusions regarding receptor sensitivity in the presence of the
baroreflex may be misleading. In 8 normal volunteers, we determined the
heart rate and blood pressure changes after incremental bolus doses of
isoproterenol, phenylephrine, and sodium nitroprusside
before and during neuronal nicotinic cholinergic
(NN-cholinergic) blockade with trimethaphan. Results are
given as median (25th/75th percentile). With trimethaphan, the
baroreflex slope (as determined by bolus doses of nitroprusside and
phenylephrine) decreased from 24 (22/26) to 0.00
(0.00/0.09) ms/mm Hg (P<0.01). The dose of
isoproterenol that decreased systolic blood pressure (SBP)
12.5 mm Hg changed from 0.61 (0.51/5.3) to 0.17 (0.12/0.21) µg
(P<0.01); the dose required to increase heart rate 12.5
bpm changed from 0.22 (0.17/0.41) to 0.74 (0.33/2.3) µg
(P<0.01). The dose of nitroprusside required to
decrease SBP 12.5 mm Hg changed from 2.3 (1.3/3.4) to 0.18
(0.14/0.24) µg/kg (P<0.01). The dose of
phenylephrine required to increase SBP 12.5 mm Hg
changed from 135 (110/200) to 16 (10/30) µg (P<0.01).
We conclude that the efferent arc of the baroreflex can be completely
interrupted with NN-cholinergic blockade. Estimation of
adrenoreceptor sensitivity and sensitivity to nitric
oxide donors by systemic administration of agonists is severely
confounded by baroreflexes. Uncoupling of the baroreflex by
NN-cholinergic blockade may be a useful method to obtain an
integrated measure of adrenergic receptor sensitivity and sensitivity
to nitric oxide donors in humans. This approach would permit the
comparison of normal and abnormal physiological
states without the "noise" of baroreflex buffering.
© 1998 American Heart Association, Inc.
Scientific Contributions
Uncoupling of the Baroreflex by NN-Cholinergic Blockade in Dissecting the Components of Cardiovascular Regulation
Key Words: receptors, adrenergic • phenylephrine • nitroprusside • isoproterenol • trimethaphan
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