Stimulation of serotonin2 receptors in the ventrolateral medulla of the cat results in nonuniform increases in sympathetic outflow.
Topical application of the serotonin2 agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane or DOI, in a dose of 30 micrograms/side to the intermediate area of the ventrolateral surface of the medulla produced a significant increase in mean arterial pressure with no significant change in heart rate both in intact animals (n = 8) and in cervically vagotomized animals (n = 3). The pressor response of DOI was blocked by pretreatment of the intermediate area with ketanserin, a serotonin2 antagonist (n = 7). Pretreatment with intravenous phentolamine did not block the pressor response of DOI (n = 3). However, this pressor response could be counteracted by intravenous propranolol (n = 5) or by bilateral stellate ganglionectomy (n = 3). These data suggest that sympathoexcitation by centrally applied DOI selectively increased cardiac inotropy but not chronotropy. Further studies indicate that DOI increased contractile force without increasing heart rate and that the positive inotropic effect of DOI could be counteracted by bilateral stellate ganglionectomy. Bilateral microinjections of DOI into the subretrofacial nucleus in a dose of 100 ng (n = 3) and a dose of 300 ng (n = 3) increased mean arterial blood pressure by 23 +/- 2 and 44 +/- 6 mm Hg, respectively, without producing any changes in heart rate. These data suggest that DOI has a central site of action in the ventrolateral medulla, presumably at the subretrofacial nucleus, which leads to selective sympathoexcitation of the cardiac ventricles.
Mandal
A K
AK
Department of Pharmacology, Georgetown University School of Medicine, Washington, D.C. 20007.
Kellar
K J
KJ
Norman
W P
WP
Gillis
R A
RA
D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure; D002415:Cats; D004562:Electrocardiography; D005260:Female; D006339:Heart Rate; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000502:physiology*; D011433:Propranolol / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000187:drug effects*; D012119:Respiration; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013268:Stimulation, Chemical; D013564:Sympathetic Nervous System / Q000502:physiology*; D013990:Tidal Volume
D000662:Amphetamines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D007650:Ketanserin; D011433:Propranolol; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine