EFFECT OF LOSARTAN ON AFFERENT NERVE-STIMULATION

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.