Satoshi Murayama

Cardiovascular effects of central administration of cholinomimetics in anesthetized cats

The cardiovascular effects of central administration of cholinomimetics were investigated in anesthetized cats, to identify the site and mechanism of their action. Physostigmine, 10-100 micrograms, given by intracerebroventricular administration (i.c.v.) caused a dose-dependent reduction in blood pressure and renal sympathetic nerve discharges and no change in heart rate, which were antagonized by intravenous injection (i.v.) of atropine but not by methscopolamine or pirenzepine, given intravenously. Carbachol 3-30 micrograms (i.c.v.) reduced blood pressure and renal sympathetic nerve discharges and caused no change in heart rate. The M1 muscarinic agonist, McN-A-343, 100-1000 micrograms (i.c.v.) did not affect blood pressure, heart rate or renal sympathetic nerve discharges. Bilateral application of physostigmine, 10-100 micrograms/site on the ventral medullary surface, decreased blood pressure and renal sympathetic nerve discharges but not heart rate. Carbachol, 3-30 micrograms/site, caused reductions in blood pressure and renal sympathetic nerve discharges and no change in heart rate. Atropine, but not pirenzepine or methscopolamine, reversed the effects of physostigmine or carbachol. Treatment with McN-A-343, 100-1000 micrograms/site, did not alter blood pressure, heart rate or renal sympathetic nerve discharges. Under pretreatment with atropine into the ventral medulla but not pirenzepine, physostigmine, given intravenously, did not influence blood pressure. It is concluded that a cholinergic mechanism, concerned with a depressor response, is located on the ventral medulla. Muscarinic receptors of the non-M1 subtype, possibly M2, are related to this mechanism.

Central cardiovascular effects of physostigmine in anesthetized cats

The central cardiovascular effects of a cholinesterase inhibitor, physostigmine, were studied in alpha-chloralose- and urethane-anesthetized cats, to determine the underlying site and mechanism of action. Intravenous injection of physostigmine produced a dose-dependent fall in blood pressure and heart rate. These responses were blocked by intravenous injection of atropine; however, the peripheral antimuscarinic agent, methscopolamine, failed to inhibit the depressor response. In decerebrated cats, physostigmine elicited similar responses in blood pressure and heart rate as in intact animals. In spinal cats, physostigmine failed to evoke any response. Physostigmine significantly reduced sympathetic nervous activity, as measured by renal sympathetic nerve discharges, indicating that the fall in blood pressure was due to a decrease in sympathetic tone. These results demonstrate that physostigmine, which crosses the blood-brain barrier, produces a depressor response through stimulation of muscarinic cholinergic receptors, located in the medullary region and that the effect is mediated by a decrease in sympathetic activity.

The spino-bulbo-spinal reflex in cats with hind-limb rigidity produced by spinal cord ischemia

The PLRF (paralemniscal pontine reticular formation) exerts a pattern control of the bilateral forelimb muscles. When repetitive electrical stimulation is applied to the PLRF on one side, coordinated movements of bilateral forelimbs are elicited. The ipsilateral forelimb is flexed and the contralateral forelimb extended. In this series of experiments, to analyze descending pathways from the PLRF to the cervical motor pools, thalamic cats were used. Thalamic cats were made by transection at Alp level under ether anesthesia. After unilateral transection was performed on the ventral quadrant at the C -C 2 level, PLRF-elicited movements of the ipsilateral forelimb disappeared bu~ extension of the contralateral forelimb remained intact. These results imply that each supraspinal descending pathway passes independently through either side of the spinal ventral funiculus. EPSPs and spike potentials were observed from motoneurons innervating the biceps brachii muscle following stimulation of the PLRF. The delayed time between descending discharges of the PLRF and PLRF-elicited epsp of motoneurons was longer than 1 ms. This means that motoneurons may be activated by descending volleys polysynaptically via spinal interneurons. Intracellular potentials were recorded from cervical interneurons following pulse train stimulation of the PLRF, monosynaptic epsp and delayed and slow depolarizations were observed. Both membrane potentials were increased in amplitude, when pulse frequency of stimulation was increased. Spikes appeared at 3rd and later pulses in train; maximal firing rate was at 4th pulse. This implies that cervical interneurons may be fired by summation of both volleys of direct and indirect pathways from the PLRF.