Cardiovascular effects elicited by central administration of physostigmine via M2 muscarinic receptors in conscious cats.

ABSTRACT

The cardiovascular effects of an intracerebroventricular (i.c.v.) injection of physostigmine were studied using conscious cats. Physostigmine (5-25 micrograms 5 microliters) caused a dose-dependent increase in mean arterial pressure (MAP) and heart rate (HR). The highest dose (25 micrograms) increased MAP and HR by 32 +/- 3 mmHg and 45 +/- 5 beats/min, respectively (n = 5). Pre-administration of the muscarinic receptor antagonist, atropine (25 micrograms; i.c.v.) blocked the effects of physostigmine (25 micrograms; i.c.v.). Also, the pre-administration of the M2 muscarinic antagonist, methoctramine (25 micrograms; i.c.v.), antagonized the cardiovascular effects of physostigmine without altering the baseline variables. However, the M1 muscarinic antagonist, pirenzepine (100 micrograms; i.c.v.) did not alter baseline MAP or HR, and also failed to inhibit the cardiovascular responses to physostigmine. Similarly, the M3 muscarinic blocker, 4-diphenyl-acetoxy-N-methylpiperidine methiodide (50 micrograms; i.c.v.), neither changed baseline cardiovascular variables nor blocked the effects of physostigmine. When the same cats were anesthetized with intravenous injection of sodium pentobarbital (25-30 mg/kg), physostigmine (25 micrograms; i.c.v.) evoked a decrease in MAP and HR of 13 +/- 6 mmHg and 15 +/- 6 bpm, respectively (n = 5). These results demonstrate that the increases in MAP and HR to the i.c.v. administration of physostigmine in conscious cats are possibly mediated through stimulation of central M2 muscarinic receptors. In addition, anesthesia reverses the effects elicited by the central administration of physostigmine to a decrease in MAP and HR.