The central action of the 5-HT2 receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) on cardiac inotropy and vascular resistance in the anaesthetized cat.
Experiments were carried out to determine the effects of the application of the selective 5-HT2 receptor agonist DOI intravenously (in the presence of the peripherally acting 5-HT2 receptor antagonist, BW501C67, 1 mg kg(-1), i.v.) or to the 'glycine sensitive area' of the ventral surface (30 microg each side) on the left ventricular inotropic (left ventricular dP/dt max) and vascularly isolated hindlimb responses in anaesthetized cats. For the ventral surface experiments, NMDA (10 microg each side) was applied to act as a positive control. In all experiments heart rate and mean arterial blood pressure were held constant to exclude any secondary effects caused by changes in these variables. DOI (n=6) i.v or on the ventral surface had no effect on left ventricular dP/dt max but caused a significant increase in hindlimb perfusion pressure of 40+/-9 and 50+/-14 mmHg, respectively. Respiration was unaffected. NMDA (n=6), applied to the ventral surface, caused significant increases in both left ventricular dP/dt max and hindlimb perfusion pressure of 1,950+/-349 mmHg s(-1) and 69+/-17 mmHg respectively, with no associated change in left ventricular end-diastolic pressure. The amplitude of respiratory movements increased. It is concluded that activation of 5-HT2 receptors at the level of the rostral ventrolateral medulla (RVLM) excites sympathetic premotor neurons and/or their antecedents controlling hindlimb vascular resistance but not those controlling the inotropic effects on the left ventricle.
Ramage
A G
AG
Department of Pharmacology, Royal Free Campus, University College London.
Daly
M B
MB
D000313:Adrenal Medulla / Q000187:drug effects / Q000502:physiology; D000578:Amidines / Q000494:pharmacology; D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002415:Cats; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D016202:N-Methylaspartate / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D012965:Sodium Chloride / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects*; D016277:Ventricular Function, Left / Q000187:drug effects
D000578:Amidines; D000662:Amphetamines; D002316:Cardiotonic Agents; D018690:Excitatory Amino Acid Agonists; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D012965:Sodium Chloride; D016202:N-Methylaspartate; C029751:BW 501C; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine