Blockade of brain M2 muscarinic receptors lowers blood pressure in spontaneously hypertensive rats.
Injections of the M2 muscarinic receptor antagonist 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP; 1.5-40 micrograms) into the cerebral ventricles of urethane-anesthetized rats caused a dose-related inhibition of the pressor response to intravenously injected physostigmine. A similar reduction was obtained with 1/80th the dose of methylatropine, but not with the selective M1 antagonist pirenzepine. Intraventricular injection of 4-DAMP (6.25-25 micrograms) caused a dose-related reduction in blood pressure in unanesthetized spontaneously hypertensive rats (SHR), but not in normotensive controls. Systolic pressure fell 42 +/- 6 mm Hg at the 25-micrograms dose. Pirenzepine did not lower blood pressure in SHR and inhibited the antihypertensive effect of 4-DAMP.
Brezenoff
H E
HE
Department of Pharmacology, University of Medicine and Dentistry of New Jersey, Newark.
Vargas
H
H
Xiao
Y F
YF
D000818:Animals; D001286:Atropine Derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D001921:Brain / Q000187:drug effects*; D008297:Male; D010276:Parasympatholytics / Q000494:pharmacology*; D010277:Parasympathomimetics / Q000494:pharmacology; D010830:Physostigmine / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D011921:Rats, Inbred WKY
D001286:Atropine Derivatives; D010276:Parasympatholytics; D010277:Parasympathomimetics; D010880:Piperidines; C006649:methylatropine; C042375:4-diphenylacetoxy-1,1-dimethylpiperidinium; D010830:Physostigmine