Cholinergic hyperactivity in the lateral septal area of spontaneously hypertensive rats: depressor effect of hemicholinium-3 and pirenzepine.
In the lateral septal area of spontaneously hypertensive rats, but not in Wistar-Kyoto rats, the selective M1 antagonist, pirenzepine, and the depletion of acetylcholine storage, by hemicholinium-3 (HC-3), decreased blood pressure. The selective M1 agonist McNeil-A-343, produced a pressor response only after treatment of the lateral septal area with HC-3 in spontaneously hypertensive rats. Carbachol, at doses that mainly affect M2 muscarinic receptors, caused no cardiovascular changes in either strain, pointing to the main intervention of the M1 subtype of muscarinic receptor in the hypertensive condition. In addition, increases in the density of binding sites for [3H]QNB and in Vmax of sodium-dependent, HC-3-inhibitable, high affinity uptake of choline were demonstrated, without significant changes of the activity of choline acetyltransferase in the lateral septal area of spontaneously hypertensive rats. These results suggest that a hyperactivity of the cholinergic system of this area could play a role in the development and/or maintenance of hypertension in spontaneously hypertensive rats.
Scheucher
A
A
Laboratorio de Sustancias Vasoactivas, Facultad de Medicina, Universidad de Buenos Aires, Argentina.
Alvarez
A L
AL
Torres
N
N
Dabsys
S M
SM
Finkielman
S
S
Nahmod
V E
VE
Pirola
C J
CJ
D008455:(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D002794:Choline / Q000378:metabolism; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006426:Hemicholinium 3 / Q000494:pharmacology*; D008297:Male; D010890:Pirenzepine / Q000494:pharmacology*; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011950:Receptors, Cholinergic / Q000378:metabolism; D012688:Septum Pellucidum / Q000502:physiology*; D013574:Synaptosomes / Q000378:metabolism
D011950:Receptors, Cholinergic; D006426:Hemicholinium 3; D010890:Pirenzepine; D008455:(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride; D011813:Quinuclidinyl Benzilate; D002795:Choline O-Acetyltransferase; D002794:Choline