Cardiovascular effects of intrathecal administration of substance P in the rat: interactions with serotonergic mechanisms.
Intrathecal (i.th.) administration of substance P (SP, 6.5 nmol) at the Th 8-10 level in conscious rats increased blood pressure (carotid artery), heart rate and plasma catecholamine concentrations. The responses were antagonized by the intravenous (i.v.) but not i.th. pretreatment with the 5-HT2-receptor antagonists ketanserin and ritanserin and intrathecally administered serotonin (5-HT, 10 micrograms). The pressor response and the increase in plasma noradrenaline concentrations were also antagonized by i.v. or i.th. pretreatment with the 5-HT1A-agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT). In contrast the pressor response to SP was facilitated by the 5-HT1A-antagonist 1-pindolol (i.v. or i.th). Pretreatment with SP (i.th) reduced the hypotensive response to i.v. 8-OH-DPAT. These results demonstrate functional interactions between SP and serotonergic mechanisms in the central system, but the precise location and nature were not elucidated.
Gradin
K
K
Department of Pharmacology, Karolinska Institute, Stockholm, Sweden.
Persson
B
B
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002395:Catecholamines / Q000097:blood; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007278:Injections, Spinal; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists; D013373:Substance P / Q000008:administration & dosage / Q000494:pharmacology*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
D002395:Catecholamines; D012702:Serotonin Antagonists; D013764:Tetrahydronaphthalenes; D012701:Serotonin; D013373:Substance P; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin