Effect of central muscarine receptor blockade with DKJ-21 on the blood pressure and heart rate in stress-induced hypertensive rats.

The experiments were performed on Wistar or Sprague-Dawley rats of both sexes divided at random into stress and control groups. The rats in the stress groups were put into cages and subjected to electric foot-shocks and noises for 9-15 days, which caused an increase in blood pressure (BP) and heart rate (HR). In hypertensive rats DKJ-21 (4 mg/1 ml) was injected intravenously (i.v.), and 0.5-1.0 h after administration the BP and HR dropped from the high level to normotensive level. In normotensive rats, however, administration of DKJ-21 had no effect on BP or HR. In separate groups of normotensive rats, pretreatment of DKJ-21 (4 mg/1 ml, i.v.) blocked the pressor and tachycardiac effect induced by microinjection of physostigmine (0.4 microgram/0.1 microliter/site), corticosterone (40 ng/0.1 microliter/site) or aldosterone (40 ng/0.1 microliter/site) into the rostral ventrolateral medulla (rVLM). Furthermore, DKJ-21 also attenuated the enhancement of the pressor response to stimulation of the defense area in the midbrain, which was induced by microinjection of drugs (mentioned above) into the rVLM. These results indicate that i.v. DKJ-21 can selectively block the muscarinic receptors in the rVLM in stress-induced hypertensive rats, which suggests that abnormal enhancement of cholinergic mechanism in the rVLM may be related to hypertensive effects of corticoids in this area.