Experimental central hypertension produced by chemical degeneration of the locus coeruleus in the rat.
The role of noradrenergic neurons originating from the locus coeruleus (LC) in blood pressure regulation was studied by stereotaxic administration of 6-hydroxydopamine (6-OHDA) into the LC in Wistar-Kyoto rats. The administration of 6-OHDA (12 micrograms/6 microliters) into the bilateral LC resulted in hypertension and tachycardia, which lasted for 12 days and gradually returned to the levels observed before administration. The systolic blood pressure and heart rate were 172 mmHg and 460 beats/min on the mean respectively, one day after administration. The induced hypertension and tachycardia were closely correlated with the depletion of norepinephrine (NE) content in the cortex and the medulla-pons in rats in a hypertensive state. The correlation between the NE content of the cortex and blood pressure was particularly marked (r = -0.793, p less than 0.02). Furthermore, destructive change of the LC was observed histologically in the hypertensive rats. They hypertension was completely prevented by pretreatment with desipramine before 6-OHDA administration. These findings suggest that 6-OHDA induced degeneration, probably mainly in the dorsal bundle originating from the LC and in the LC itself. It is suggested, therefore, that localized chemical degeneration of the bilateral LC causes hypertension and tachycardia as a consequence of denervation of the dorsal bundle of noradrenergic neurons originating from the LC.
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure; D005260:Female; D006339:Heart Rate; D006892:Hydroxydopamines / Q000494:pharmacology; D006973:Hypertension / Q000209:etiology*; D008125:Locus Coeruleus / Q000032:analysis / Q000502:physiology*; D008297:Male; D009410:Nerve Degeneration; D009638:Norepinephrine / Q000032:analysis; D051381:Rats; D012737:Sex Factors; D013045:Species Specificity
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D006892:Hydroxydopamines; D009638:Norepinephrine