Interaction between noradrenergic and serotonergic mechanisms on the central regulation of blood pressure in the rat: a study using experimental central hypertension produced by chemical lesions of the locus coeruleus.
The interaction between noradrenergic and serotonergic mechanisms on the central regulation of blood pressure in the rat was studied, using central experimental hypertension produced by chemical lesions of the locus coeruleus (LC) with 6-hydroxydopamine (6-OHDA). The hypertension (LC-hypertension) was blocked by pretreatment with 6-OHDA intraventricularlly administered and also with desipramine. An increase of serotonin (5-HT) turnover in the cortex and especially in the spinal cord was revealed in the hypertension. Intraperitoneally administered para-chlorophenylalanine elevated blood pressure and reduced 5-HT and 5-hydroxyindole acetic acid content in the cortex and especially in the spinal cord, indicating a decrease 5-HT turnover. Intraventricularlly administered 5, 6-dihydroxytryptamine (5, 6-DHT) resulted in only bradycardia but not an elevation in blood pressure and did not block the development of LC hypertension, and lowered 5-HT content in the cortex and especially in the spinal cord. Intraspinally administrated 5, 6-DHT evoked mild but significant elevation in blood pressure but not in heart rate, and lowered 5-HT content only in the spinal cord. Furthermore, the disappearance of the LC was histologically observed in the rats with LC hypertension. The results of these experiments demonstrate that (1) LC hypertension is probably due to a specific lesion of the LC with 6-OHDA, (2) LC hypertension is accompanied by an increase of 5-HT turnover in the cortex and especially in the spinal cord, which may participate in a depressor function in LC hypertension, (3) ablation of bulbospinal serotonergic neurons produce mild elevation in blood pressure. (4) the balance between the activity of central noradrenerfic and serotonergic neurons may play a role in maintaining normotension, and their unbalance may induce hypertension.
D015115:5,6-Dihydroxytryptamine / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001923:Brain Chemistry; D003891:Desipramine / Q000494:pharmacology; D010134:Fenclonine / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006892:Hydroxydopamines / Q000008:administration & dosage / Q000494:pharmacology; D006897:Hydroxyindoleacetic Acid / Q000032:analysis; D006973:Hypertension / Q000209:etiology* / Q000378:metabolism; D008125:Locus Coeruleus / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009474:Neurons / Q000032:analysis / Q000502:physiology; D009638:Norepinephrine / Q000032:analysis / Q000502:physiology*; D051381:Rats; D012701:Serotonin / Q000032:analysis / Q000502:physiology*; D013116:Spinal Cord / Q000032:analysis
D006892:Hydroxydopamines; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D010134:Fenclonine; D003891:Desipramine; D015115:5,6-Dihydroxytryptamine; D009638:Norepinephrine