Cardiovascular effects of intrathecal administration of agents active at 5-hydroxytryptamine1-receptors in the rat: modulation by substance P and a substance P antagonist.
The intrathecal (i.th., T8-10) administration in conscious rats of the 5-hydroxytryptamine (5-HT)1A agonist 8-OH-DPAT (10 nmol), and to a lesser extent the 5-HT1B agonist CGS 12066B (6 nmol), resulted in a blood pressure reduction and a bradycardia. These responses were prevented by the i.th. pretreatment with substance P (SP) (6.5 nmol) and enhanced following pretreatment with the non-peptide SP antagonist CP-96,345 (10 nmol). The partial 5-HT1A agonist 8-MeO-CLEPAT (10 nmol) had by itself small cardiovascular effects. Following the pretreatment with SP, 8-MeO-CLEPAT caused a pressor response and a tachycardia whereas the opposite effects were observed following pretreatment with the SP antagonist. These results support the notion of a functional interaction between serotonergic and SP mechanisms at the level of the preganglionic sympathetic nerves in the spinal cord.
Gradin
K
K
Department of Pharmacology, Karolinska Institute, Stockholm, Sweden.
Persson
B
B
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects*; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D007278:Injections, Spinal; D008297:Male; D011810:Quinoxalines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*; D013373:Substance P / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage / Q000494:pharmacology; D013997:Time Factors
D001713:Biphenyl Compounds; D006993:Hypnotics and Sedatives; D011810:Quinoxalines; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D013764:Tetrahydronaphthalenes; C052561:CGS 12066B; C084326:8-methoxy-2-(N-2-chloroethyl-N-n-propyl)aminotetralin; D013373:Substance P; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C066892:CP 96345