Changes in neurotransmitter turnover in locus coeruleus produced by changes in arterial blood pressure.
The effect of drug-induced hypertension and hypotension on neurotransmitter metabolism in the locus coeruleus (LC) of urethane anesthetized rats was studied using in vivo electrochemical methods. Peaks were seen at +0.15 V and +0.28 V. Studies with alpha-methylparatyrosine, fusaric acid and pargyline showed the first peak was produced by extracellular fluid dihydroxyphenylacetic acid (DOPAC) while the second peak was 5-hydroxyindoleacetic acid (5-HIAA). Phenylephrine was infused intravenously to raise the blood pressure by 50 mmHg, nitroprusside IV was used to reduce the blood pressure by 20 mmHg. During phenylephrine hypertension, the electrochemical signal for DOPAC showed an initial small reduction followed by a later significant increase which persisted even after the infusion was stopped. The signal for 5-HIAA rose with the onset of hypertension and remained elevated. Nitroprusside hypotension did not change the DOPAC peak but did lead to an immediate and persistent increase in the electrochemical 5-HIAA peak. To confirm the electrochemical findings, other groups of rats were decapitated during and after hypertensive and hypotensive drug infusions and the LC was assayed for norepinephrine, dopamine, DOPAC, serotonin, and 5-HIAA using HPLC with electrochemical detection. Changes in tissue DOPAC and 5-HIAA concentrations supported the electrochemical electrode observations. The effect of clonidine on the electrochemical recordings from LC was also studied. Clonidine reduced the catechol peak. No change was observed in the 5-HIAA peak during the infusion, but the 5-HIAA peak went up after the infusion was stopped. These experiments show that hypertension, hypotension, and alpha-2 agonists lead to changes in catecholamine and indoleamine metabolism in LC.
Bhaskaran
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Department of Medicine, University of Colorado Health Sciences Center, Denver 80262.
Freed
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D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D006973:Hypertension / Q000378:metabolism*; D007022:Hypotension / Q000378:metabolism*; D008125:Locus Coeruleus / Q000378:metabolism*; D008297:Male; D018377:Neurotransmitter Agents / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D018377:Neurotransmitter Agents; D015102:3,4-Dihydroxyphenylacetic Acid; D006897:Hydroxyindoleacetic Acid