The present study was undertaken to investigate the effects of losarta
n, a non-peptide angiotensin II subtype 1 (AT(1)) receptor antagonist,
on both the presser responses elicited by stimulation of afferent vag
al nociceptive fibres and the involvement of the sympathetic nervous s
ystem (evaluated by plasma levels of noradrenaline and its co-neurotra
nsmitter neuropeptide Y) in dogs. Electrical stimulation of the affere
nt fibres of the vagus (1, 5, 10 and 20 Hz) elicited a frequency-depen
dent increase in blood pressure and heart rate. Plasma noradrenaline l
evels only increased after stimulation at frequencies of 10 and 20 Hz.
Plasma neuropeptide Y levels did not change. Losartan (10 mg/kg i.v.)
induced both a decrease in resting blood pressure and an increase in
basal plasma levels of noradrenaline and neuropeptide Y. Losartan fail
ed to modify the magnitude of the electrically-evoked presser and posi
tive chronotropic responses. The angiotensin AT(1) receptor antagonist
elicited a fall in plasma noradrenaline values after a 1 Hz stimulati
on and abolished the increase in plasma noradrenaline levels induced b
y the 10 (but not 20) Hz stimulation. The data suggest that angiotensi
n AT, receptors are not directly involved in acute presser responses i
nduced by stimulation of afferent vagal fibres. Moreover, the results
show that, besides its sympatho-inhibitory effect, losartan can exert
a sympatho-excitatory action as shown by the increase in the plasma le
vels of both noradrenaline and its coneurotransmitter, neuropeptide Y.
(C) 1998 Elsevier Science B.V. All rights reserved.