Effect of losartan on afferent nerve stimulation.
The present study was undertaken to investigate the effects of losartan, a non-peptide angiotensin II subtype 1 (AT1) receptor antagonist, on both the pressor responses elicited by stimulation of afferent vagal nociceptive fibres and the involvement of the sympathetic nervous system (evaluated by plasma levels of noradrenaline and its co-neurotransmitter neuropeptide Y) in dogs. Electrical stimulation of the afferent fibres of the vagus (1, 5, 10 and 20 Hz) elicited a frequency-dependent increase in blood pressure and heart rate. Plasma noradrenaline levels 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 failed to modify the magnitude of the electrically-evoked pressor and positive chronotropic responses. The angiotensin AT1 receptor antagonist elicited a fall in plasma noradrenaline values after a 1 Hz stimulation and abolished the increase in plasma noradrenaline levels induced by the 10 (but not 20) Hz stimulation. The data suggest that angiotensin AT1 receptors are not directly involved in acute pressor responses induced 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 levels of both noradrenaline and its coneurotransmitter, neuropeptide Y.
Laboratoire de Pharmacologie Médicale et Clinique, INSERM U 317, Faculté de Médecine, Toulouse, France. damase@cict.fr
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C
Damase-Michel
M A
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Tran
J L
JL
Montastruc
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P
Montastruc
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D004285:Dogs; D004558:Electric Stimulation; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects* / Q000502:physiology; D009478:Neuropeptide Y / Q000097:blood*; D009638:Norepinephrine / Q000097:blood*; D013268:Stimulation, Chemical; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D009478:Neuropeptide Y; D019808:Losartan; D009638:Norepinephrine