Blood pressure response in rats to intracisternal administration of choline.

Central administration of acetylcholine or nicotine to rats induces changes in blood pressure and heart rate via central chol inoceptor activation (1, 2). Physostigmine a cholinesterase inhibitor also modifies blood pressure and heart rate (3, 4). Thus, central cholinergic mechanisms may be physio logically involved in the central control of cardiovascular function. In the present experiments, we studied the cardiovascular effects of choline injected into the cisterna magna. Male Wistar rats, weighing 250-300 g, were anaesthetized with urethane (1.2 g/kg, i.p.). The left femoral artery and femoral vein were cannulated and then the head was fixed downward at an angle of 45° in a stereotaxic apparatus. A polyethylene cannula was introduced into the cisterna magna for intracisternal injections. Throughout each experiment, the rectal temperature was main tained at about 36'C. Blood pressure recordings were made via the femoral cannula using a pressure transducer (Sanei Model M PU-0.5-290) connected to a Sanei recorder. Mean blood pressure was calculated as diastolic pressure+1 /3 (systolic pressure minus diastolic pressure). Heart rate was continuously computed from the blood pressure pulse wave by a card 1otachometer (Sanei-2140). Drugs were dissolved in 0.9% NaCl solution and were administered intra cisternally in a volume of 5 /dl. The following drugs were used: choline chloride (Sigma), atropine sulphate (E. Merck), hexarnethonium bromide (Yamanouchi Pharmaceutical), physostigmine salicylate (E. Merck), hemi cholinium-3 (Aldrich Chemical). All doses of drugs refer to the free base. Control mean blood pressure was 96+3 mmHg (means+S.E. from 35 experiments) and heart rate was 376+9 beats/min (n=35). Choline (12.5, 25 and 50 /eg), injected into the cisterna magna, produced a decrease in blood pressure by 11±2 mmHg (n=5), 18±2 mmHg (n=5) and 35±4 mmHg (n=5), respectively, and such decreases were accompanied by a decrease in heart rate by 10+3 beats/min, 3114 beats/min and 52+6 beats/min, respectively. The hypotensive response began 20-40 sec after injection of choline and reached a maximum within 2 min. With the highest dose, the depressor response was followed by a slight pressor response (5-8 mmHg) which was too small for analysis (Fig. 1). Intravenous administration of choline (50 iig) produced no observable cardiovascular effect. When choline (50 ag) was injected into the cisterna magna at intervals of 30 min, the depressor response was not appreciably altered. In 5 experiments, hexamethonium (20 peg), given intracisternally 5 min before the second administration of choline (50 i g), abolished the blood pressure responses to choline …