Evidence that the novel antihypertensive agent, flesinoxan, causes differential sympathoinhibition and also increases vagal tone by a central action.
The effects of flesinoxan were studied on thoracic preganglionic, splanchnic and renal sympathetic nerve activity, carotid sinus nerve activity, blood pressure and heart rate in anaesthetised cats. In some experiments femoral or renal arterial conductance was also recorded. Flesinoxan (3-300 micrograms kg-1) caused a dose-related fall in blood pressure and heart rate and also caused sympathoinhibition. This fall in blood pressure was not associated with changes in femoral arterial conductance but was with a large increase in renal arterial conductance. In this respect flesinoxan had a greater sympathoinhibitory action on the renal nerve compared with the other sympathetic outflows. The bradycardia was unaffected by the 5-HT3 antagonist, MDL 72222, but was reversed by atropine and was abolished in bi-vagotomised cats. Flesinoxan also caused sympathoinhibition in bi-vagotomised cats and decreased carotid sinus nerve activity and blood pressure. It is concluded that flesinoxan acts centrally to cause sympathoinhibition and an increase in vagal tone.
Ramage
A G
AG
Academic Department of Pharmacology, Royal Free Hospital School of Medicine, Hampstead, London, U.K.
Wouters
W
W
Bevan
P
P
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000502:physiology; D002415:Cats; D005725:Ganglia, Autonomic / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D007668:Kidney / Q000294:innervation; D009431:Neural Conduction / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology*; D013153:Splanchnic Nerves / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000187:drug effects*; D014628:Vagotomy; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology*
D000959:Antihypertensive Agents; D010879:Piperazines; C056895:flesinoxan