Suppression of hypertension during chronic reduction of brain acetylcholine in spontaneously hypertensive rats.
Experiments were conducted to determine the effects of chronic depletion of brain acetylcholine (ACh) on the development and maintenance of hypertension in spontaneously hypertensive rats (SHR). Synthesis of brain ACh was inhibited by chronic infusion of hemicholinium-3 (HC-3) into the cerebral ventricles, and systolic blood pressure was monitored by tail cuff occlusion. In 5-week-old SHR, infusion of HC-3 (0.25 micrograms/h) suppressed development of hypertension when compared to saline-infused control SHR during the 21 days of infusion (140 versus 190 mmHg on day 21). Hypothalamic and brain-stem ACh during this period was reduced by 50% and by 60-75%, respectively. In 18-week-old SHR with established hypertension, HC-3 (0.25 and 0.5 micrograms/h) reduced systolic blood pressure by 35-40 mmHg for 8 days, after which pressures returned to control hypertensive levels (191 mmHg) by day 14. The increase in blood pressure was accompanied by recovery of hypothalamic ACh levels to 75% of control. The specificity and physiological effectiveness of HC-3 was shown by its ability to inhibit the centrally mediated pressor response to physostigmine but not to oxotremorine. Infusion of HC-3 did not affect body growth, water consumption, body temperature or gross behavior. From this study, it can be concluded that brain cholinergic neurons are an important component in the development and the maintenance of hypertension in the SHR.
Vargas
H M
HM
Department of Pharmacology, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark 07103.
Brezenoff
H E
HE
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D002552:Cerebral Ventricles; D006426:Hemicholinium 3 / Q000008:administration & dosage / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D006973:Hypertension / Q000209:etiology* / Q000378:metabolism; D007262:Infusions, Intravenous; D008297:Male; D010095:Oxotremorine / Q000494:pharmacology; D010830:Physostigmine / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011950:Receptors, Cholinergic / Q000378:metabolism
D011950:Receptors, Cholinergic; D006426:Hemicholinium 3; D010095:Oxotremorine; D010830:Physostigmine; D000109:Acetylcholine