The involvement of central cholinergic system in the pressor effect of intracerebroventricularly injected U-46619, a thromboxane A2 analog, in conscious normotensive rats.
The aim of this study was to determine the involvement of the central cholinergic system in the rise in blood pressure evoked by the thromboxane A2 (TxA2) analog, U-46619, given centrally. Intracerebroventricular (i.c.v.) injections of U-46619 (0.5, 1.0 and 2.0 microg) caused dose- and time-related increases in blood pressure and decreased heart rate in awake rats. U-46619 (1 microg; i.c.v.) also produced an approximately 65% increase in posterior hypothalamic extracellular acetylcholine and choline levels. Pretreatment with SQ-29548 (8 microg; i.c.v.), selective TxA2 receptor antagonist, completely inhibited both the cardiovascular responses and the increase in acetylcholine and choline levels to subsequent injection of U-46619 (1 microg; i.c.v.). Atropine (10 microg; i.c.v.), nonselective muscarinic receptor antagonist, pretreatment did not affect the cardiovascular responses observed after U-46619 (1 microg; i.c.v.). Pretreatment with the nonselective nicotinic receptor antagonist, mecamylamine (50 microg; i.c.v.) attenuated the pressor effect of U-46619 (1 microg; i.c.v.). Higher doses of mecamylamine (75 and 100 microg; i.c.v.) pretreatments did not change the magnitude of the blockade of pressor response to U-46619; however, they abolished the bradycardic effect of U-46619 dose-dependently. Interestingly, pretreatment of rats with methyllycaconitine (10 microg; i.c.v.) or alpha-bungarotoxin (10 microg; i.c.v.), selective antagonists of alpha7 subtype of nicotinic acetylcholine receptors (alpha7nAChRs), partially abolished the pressor response to i.c.v. injection of U-46619 (1 microg). Similar to the mecamylamine data, the use of higher doses of methyllycaconitine (25 and 50 microg; i.c.v.) produced the same magnitude of blockade that was observed after the 10 microg methyllycaconitine pretreatment, but it completely abolished the bradycardic effect of U-46619 (1 microg; i.c.v.) at the dose of 25 microg. The present results show that central administration of U-46619 produces pressor and bradycardic effect and increase in hypothalamic acetylcholine and choline levels by activating central TxA2 receptors. The activation of central nicotinic receptors, predominantly alpha7nAChRs, partially mediates the cardiovascular responses to i.c.v. injection of U-46619.
Yalcin
Murat
M
Department of Physiology, Uludag University Veterinary Faculty, 16059, Gorukle, Bursa, Turkey.
Cavun
Sinan
S
Yilmaz
M Sertac
MS
Savci
Vahide
V
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D000109:Acetylcholine / Q000378:metabolism; D000157:Aconitine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002038:Bungarotoxins / Q000008:administration & dosage; D002490:Central Nervous System / Q000187:drug effects* / Q000378:metabolism; D002794:Choline / Q000378:metabolism; D005231:Fatty Acids, Unsaturated; D006339:Heart Rate / Q000187:drug effects; D006834:Hydrazines / Q000008:administration & dosage; D007034:Hypothalamus, Posterior / Q000187:drug effects* / Q000378:metabolism; D007276:Injections, Intraventricular; D008297:Male; D008464:Mecamylamine / Q000008:administration & dosage; D018733:Nicotinic Antagonists / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000187:drug effects; D044244:Receptors, Thromboxane A2, Prostaglandin H2 / Q000037:antagonists & inhibitors; D013997:Time Factors; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000494:pharmacology*; D064569:alpha7 Nicotinic Acetylcholine Receptor
D019086:Bridged Bicyclo Compounds, Heterocyclic; D002038:Bungarotoxins; C579165:Chrna7 protein, rat; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D014662:Vasoconstrictor Agents; D064569:alpha7 Nicotinic Acetylcholine Receptor; C054634:methyllycaconitine; D008464:Mecamylamine; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C045749:SQ 29548; D002794:Choline; D000109:Acetylcholine; D000157:Aconitine