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.
Ally
A
A
Department of Pharmacology, School of Medicine, Chiba University, Japan.
Hara
Y
Y
Murayama
S
S
D008455:(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride / Q000494:pharmacology; D000287:Administration, Topical; D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002217:Carbachol / Q000494:pharmacology; D002415:Cats; D004305:Dose-Response Relationship, Drug; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007276:Injections, Intraventricular; D007668:Kidney / Q000294:innervation; D008297:Male; D008526:Medulla Oblongata; D010277:Parasympathomimetics / Q000494:pharmacology*; D010830:Physostigmine / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000187:drug effects; D013238:Stereotaxic Techniques
D010277:Parasympathomimetics; D011976:Receptors, Muscarinic; D008455:(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride; D002217:Carbachol; D010830:Physostigmine