CARDIOVASCULAR EFFECTS OF CENTRALLY INJECTED TETRAHYDROAMINOACRIDINE IN CONSCIOUS NORMOTENSIVE RATS

In freely moving rats, intracerebroventriculary (i.c.v.) injected tetr ahydroaminoacridine (10, 25, 50 mu g) increased blood pressure and dec reased heart rate in a dose-and time-dependent manner. Intravenous (i. v.) tetrahydroaminoacridine (1 and 3 mg/kg) also increased blood press ure. Atropine sulphate(10 mu g; i.c.v.) pretreatment greatly attenuate d the blood pressure response to i.c.v. tetrahydroaminoacridine while mecamylamine (50 mu g; i.c.v.) failed to change the presser effect. Ne ither atropine sulphate nor mecamylamine pretreatment affected the bra dycardia induced by tetrahydroaminoacridine. However, the bradycardic response was completely blocked by atropine methylnitrate (2 mg/kg; i. p.) pretreatment. The presser response to i.c.v. tetrahydroaminoacridi ne was associated with a several-fold increase in plasma levels of vas opressin, adrenaline and noradrenaline, but not of plasma renin. Pretr eatment with prazosin (0.5 mg/kg; i.v.) attenuated the presser effect without changing the bradycardia. Vasopressin V-1 receptor antagonist [beta-mercapto-beta, beta-cyclopentamethylenepropionyl(1), O-Me-Tyr(2) -Arg(8)]vasopressin (10 mu g/kg; i.v.) pretreatment also partially inh ibited the presser response to i.c.v. tetrahydroaminoacridine and abol ished the bradycardia. Tetrahydroaminoacridine's cardiovascular effect s were completely blocked when rats were pretreated with prazosin plus vasopressin antagonist. The data show that tetrahydroaminoacridine in creases blood pressure in normotensive freely moving rats by activatin g central muscarinic cholinergic transmission. Increases in plasma cat echolamines and vasopressin are both involved in this response. The te trahydroaminoacridine-induced reduction in heart rate appears to be du e to the increase in vagal tone and plasma vasopressin. (C) 1998 Elsev ier Science B.V.