Effect of hemicholinium-3 on the hypothalamic concentration of a cytochemically detectable glucose-6-phosphate dehydrogenase-stimulating substance.
Hypothalamus and plasma of salt-loaded rats, spontaneously hypertensive rats (SHR), and hypertensive reduced renal mass rats (RRM), and the plasma of patients with essential hypertension and of Milan hypertensive rats contain an increased concentration of a cytochemically detectable glucose-6-phosphate dehydrogenase (G6PD)-stimulating substance that has properties similar to that of a possible choline derivative di-methyl methylene immonium ion. Intracerebroventricular (i.c.v.) administration of hemicholinium-3 (HC-3) selectively blocks high-affinity neuronal choline uptake, inhibits brain acetylcholine (ACh) synthesis, and decreases arterial pressure in SHR through an inhibiting effect on hypothalamic cholinergic function. The experiments were performed to study the effect of centrally administered HC-3 on the content of the cytochemically detectable cholinelike substance in hypothalamus and plasma of SHR. HC-3 or saline was infused into the lateral cerebral ventricle for 6 days with a minipump in 14 SHR. On day 7, the hypothalamic and plasma concentration of the cytochemically detectable substance was significantly reduced in rats that received HC-3. The hypothalamic concentration was 225 +/- 95.6 x 10(8) G6PD U per hypothalamus (range 38.2-775) in SHR that received saline and 1.037 +/- 0.45 x 10(8) G6PD U (range 0.112-3.61) (p < 0.05) in SHR that received HC-3. The respective plasma concentrations were 284.9 +/- 26 U/ml (range 192-374) and 72.7 +/- 14.7 U/ml (range 24-119) (p < 0.05). The findings are consistent with the physicochemical evidence, which suggests that the cytochemically detectable substance is a choline derivative.(ABSTRACT TRUNCATED AT 250 WORDS)
Vargas
H M
HM
Biological Research Department, Hoechst-Roussel Pharmaceutical, Somerville, New Jersey.
Brezenoff
H E
HE
Morris
H R
HR
Panico
M
M
Etienne
A
A
Challand
G S
GS
Holland
S M
SM
Alaghband Zadeh
J
J
de Wardener
H E
HE
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002794:Choline / Q000378:metabolism; D004789:Enzyme Activation; D005954:Glucosephosphate Dehydrogenase / Q000097:blood / Q000378:metabolism*; D006168:Guinea Pigs; D006426:Hemicholinium 3 / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D006651:Histocytochemistry; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000201:enzymology; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D015918:Infusion Pumps, Implantable; D007276:Injections, Intraventricular; D007668:Kidney / Q000201:enzymology; D008297:Male; D009995:Osmosis; D051381:Rats; D011918:Rats, Inbred SHR
D006426:Hemicholinium 3; D005954:Glucosephosphate Dehydrogenase; D002794:Choline; D000109:Acetylcholine