Cardiovascular effects of centrally injected tetrahydroaminoacridine in conscious normotensive rats.
In freely moving rats, intracerebroventricularly (i.c.v.) injected tetrahydroaminoacridine (10, 25, 50 microg) increased blood pressure and decreased heart rate in a dose- and time-dependent manner. Intravenous (i.v.) tetrahydroaminoacridine (1 and 3 mg/kg) also increased blood pressure. Atropine sulphate (10 microg; i.c.v.) pretreatment greatly attenuated the blood pressure response to i.c.v. tetrahydroaminoacridine while mecamylamine (50 microg; i.c.v.) failed to change the pressor effect. Neither atropine sulphate nor mecamylamine pretreatment affected the bradycardia induced by tetrahydroaminoacridine. However, the bradycardic response was completely blocked by atropine methylnitrate (2 mg/kg; i.p.) pretreatment. The pressor response to i.c.v. tetrahydroaminoacridine was associated with a several-fold increase in plasma levels of vasopressin, adrenaline and noradrenaline, but not of plasma renin. Pretreatment with prazosin (0.5 mg/kg; i.v.) attenuated the pressor effect without changing the bradycardia. Vasopressin V1 receptor antagonist [beta-mercapto-beta,beta-cyclopentamethylenepropionyl1,O-Me-Tyr2-A rg8]vasopressin (10 microg/kg; i.v.) pretreatment also partially inhibited the pressor response to i.c.v. tetrahydroaminoacridine and abolished the bradycardia. Tetrahydroaminoacridine's cardiovascular effects were completely blocked when rats were pretreated with prazosin plus vasopressin antagonist. The data show that tetrahydroaminoacridine increases blood pressure in normotensive freely moving rats by activating central muscarinic cholinergic transmission. Increases in plasma catecholamines and vasopressin are both involved in this response. The tetrahydroaminoacridine-induced reduction in heart rate appears to be due to the increase in vagal tone and plasma vasopressin.
Savci
V
V
Uludag University, Medical Faculty, Department of Pharmacology, Görükle, Bursa, Turkey. vsavci@uu20.bim.uludag.edu.tr
Gürün
M S
MS
Cavun
S
S
Ulus
I H
IH
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D004837:Epinephrine / Q000097:blood; D006339:Heart Rate / Q000187:drug effects*; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D008297:Male; D009638:Norepinephrine / Q000097:blood; D011224:Prazosin / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000502:physiology; D011978:Receptors, Nicotinic / Q000502:physiology; D012083:Renin / Q000097:blood; D013619:Tacrine / Q000008:administration & dosage / Q000494:pharmacology*; D014667:Vasopressins / Q000037:antagonists & inhibitors / Q000097:blood
D002800:Cholinesterase Inhibitors; D011976:Receptors, Muscarinic; D011978:Receptors, Nicotinic; D014667:Vasopressins; D013619:Tacrine; D001285:Atropine; D012083:Renin; D009638:Norepinephrine; D011224:Prazosin; D004837:Epinephrine