CARDIOVASCULAR EFFECTS ELICITED BY CENTRAL ADMINISTRATION OF PHYSOSTIGMINE VIA M(2) MUSCARINIC RECEPTORS IN CONSCIOUS CATS

The cardiovascular effects of an intracerebroventricular (i.c.v.) inje ction of physostigmine were studied using conscious cats. Physostigmin e (5-25 mu g: 5 mu l) caused a dose-dependent increase in mean arteria l pressure (MAP) and heart rate (HR). The highest dose (25 mu g) incre ased MAP and HR by 32 +/- 3 mmHg and 45 +/- 5 beats/min, respectively (n = 5). Pre-administration of the muscarinic receptor antagonist, atr opine (25 mu g; i.c.v.) blocked the effects of physostigmine (25 mu g; i.c.v.). Also, the pre-administration of the M(2) muscarinic antagoni st, methoctramine (25 mu g; i.c.v.), antagonized the cardiovascular ef fects of physostigmine without altering the baseline variables. Howeve r, the M(2) muscarinic antagonist, pirenzepine (100 mu g; i.c.v.) did not alter baseline MAP or HR, and also failed to inhibit the cardiovas cular responses to physostigmine. Similarly, the M(3) muscarinic block er, 4-diphenyl-acetoxy-N-methylpiperidine methiodide (50 mu g; i.c.v.) , neither changed baseline cardiovascular variables nor blocked the ef fects of physostigmine. When the same cats were anesthetized with intr avenous injection of sodium pentobarbital (25-30 mg/kg), physostigmine (25 mu g; i.c.v.) evoked a decrease in MAP and HR of 13 +/- 6 mmHg an d 15 +/- 6 bpm, respectively (n = 5). These results demonstrate that t he increases in MAP and HR to the i.c.v. administration of physostigmi ne in conscious cats are possibly mediated through stimulation of cent ral M(2) muscarinic receptors. In addition, anesthesia reverses the ef fects elicited by the central administration of physostigmine to a dec rease in MAP and HR.