Arginine vasopressin and baroreflex function after converting
enzyme inhibition in normal humans.
D., Steven R. Goldsmith M., .
Hennepin County Medical Center and the University of Minnesota,
Minneapolis, Minnesota
APStracts 3:0225E, 1996.
Background Arginine vasopressin (AVP) has been shown to interact with
sinoaortic and cardiac reflexes under selected experimental
conditions. In humans, there is no evidence that AVP potentiates
reflex function at modestly increased plasma levels, except possibly
if the angiotensin converting enzyme is inhibited. Objective To test
the hypothesis that a modest physiologic increase in plasma AVP would
potentiate the responses of heart rate (HR), forearm vascular
resistance (FVR), plasma norepinephrine (NE) or systemic NE spillover
to baroreflex unloading and loading following pretreatment with
lisinopril in healthy human volunteers. Methods Seven normal young
men were studied on three occasions. Baseline HR, FVR and steady
state NE kinetics were established and AVP or vehicle (5% dextrose in
water) were infused for 15 minutes double-blind on the first two
days. Baroreflexes were then perturbed as follows: 15 minutes 60
head-up tilt, 15 minutes 30 head-down tilt plus 1000 cc normal saline
infusion, 15 minutes 30 head-down tilt plus phenylephrine titrated to
raise mean arterial pressure 10-15 mm Hg. All variables were
reassessed after each interaction. The study was repeated on a third
day 12 hours after 5 mg of lisinopril. Five additional subjects
underwent similar baroreflex study on two days with lisinopril and
placebo given double-blind, without AVP infusion. Results Prior to
baroreflex deactivation and activation, AVP had no effect on any
variable compared to vehicle. During AVP infusion after lisinopril,
HR decreased from 67 +/- 6.5 to 62 +/- 4.5 beats/min., p < 05.
AVP had no effect on the responses of any variable during baroreflex
perturbation relative to vehicle, although a trend was present for
restrained, not potentiated responses. Lisinopril pretreatment did
not unmask any positive or negative effects of AVP on reflex
function, and in the second five subjects, had no independent effect
on these responses relative to placebo. Conclusion At modestly
increased plasma levels, AVP had no discernible effect on the
responses of HR, FVR, plasma NE, or systemic NE spillover to
baroreflex deactivation and activation over the ranges employed in
these studies. After lisinopril, AVP infusion produced a modest
bradycardia, but still had no significant positive effect on any
response to baroreflex deactivation and activation. These data
suggest that inhibition of the angiotensin converting enzyme may
unmask mild direct or vagally mediated effects of AVP on HR, but does
not reveal baroreflex potentiation over the range of stimuli
delivered.
Received 16 April 1996; accepted in final form 5 November 1996.
APS Manuscript Number E187-6.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 13 November 1996