Can the 5-HT2/1c agonist DOI cause differential sympatho-excitation in nerves supplying the heart in anaesthetized cats?
A comparison of the effects on sympathetic nerve activity to the heart of intravenous administration of the selective 5-HT2/1c agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) alone and in the presence of the peripherally acting 5-HT2/1c antagonist BW501C67 were made in alpha-chloralose anaesthetized cats. Activity in both cardiac sympathetic nerves running in the vagus and in both inferior cardiac nerves was simultaneously recorded. In addition renal and phrenic nerve activity, heart rate, arterial blood pressure, femoral arterial flow and tracheal pressure were also recorded. DOI evoked a rise in blood pressure and increased femoral arterial resistance in both groups of animals. In the BW501C67 pretreated animals, DOI had no effect on heart rate but caused a significant increase in all sympathetic nerve activities. In non-pretreated animals, however, the rise in blood pressure was associated with variable effects on sympathetic nerve activity, a significant rise only occurring in renal nerve activity. In these experiments DOI evoked a bradycardia. The variability in sympathetic nerve activity in the non-pretreated animals may have resulted from the rise in blood pressure evoking a baroreceptor-mediated central sympathoinhibition which would interfere with the central sympathoexcitatory effects of DOI. It is concluded that centrally, DOI will cause sympathoexcitation. In addition, intravenous DOI acting on 5-HT2 receptors on bronchial smooth muscle evokes bronchoconstriction as indicated by the very large rise in tracheal pressure in non-BW501C67-pretreated animals. If not controlled this severely compromises respiration leading to a large overestimate of the sympathoexcitatory effects of stimulation of central 5-HT2/1c receptors.
Ramage
A G
AG
Academic Department of Pharmacology, Royal Free Hospital School of Medicine, Hampstead, London, UK.
Shepheard
S L
SL
Jordan
D
D
Koss
M C
MC
D000578:Amidines / Q000494:pharmacology; D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D016084:Bronchoconstriction / Q000187:drug effects; D002415:Cats; D005263:Femoral Artery / Q000187:drug effects; D006321:Heart / Q000187:drug effects / Q000294:innervation* / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects*; D007275:Injections, Intravenous; D008297:Male; D009474:Neurons / Q000187:drug effects; D010791:Phrenic Nerve / Q000187:drug effects; D011985:Receptors, Serotonin / Q000187:drug effects*; D012039:Regional Blood Flow / Q000187:drug effects; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D014655:Vascular Resistance / Q000187:drug effects
D000578:Amidines; D000662:Amphetamines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C029751:BW 501C; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine