Crystalline serotonin: port, M. M., Green A. A., and Page, I. H.: Science 108:329 (Sept. 24), 1948

Abstract

Spontaneously hypertensive (SH) rats were treated either acutely or chronically with 6-hydroxydopamine (6-OHDA). Thereafter, blood pressure, tissue levels of norepinephrine (NE), and vascular responses were studied.After a single, acute injection of 6-OHDA (100 mgkg) the mean arterial pressure of SH rats fell from 159 mmHg to 110–120 mmHg. This fall in pressure was accompanied by a loss of sympathetic nerve terminal function, as indicated by a loss of pressor responses to injected tyramine.After chronic 6-OHDA treatment (four injections over a period of 10 days; cumulative dose of 250 mgkg), the systolic blood pressure of SH rats fell from 185 mmHg to a variable level of approximately 125 mmHg. Tissue levels of NE in heart, aorta and mesentery were reduced, and pressor responses to tyramine were nearly abolished.Spontaneously hypertensive and normotensive (NT) rats were tested for their vasodepressor responses to prostaglandin E2 (PGE2). Spontaneously hypertensive rats were significantly more responsive to the drug than were NT rats. After acute or chronic 6-OHDA treatment, SH and NT rats had reduced responses to PGE2; the reduction was greater for SH than for NT rats.Spontaneously hypertensive and NT rats were also tested for their pressor responses to NE. The two groups of animals were equally responsive to this amine. After chronic 6-OHDA treatment, both SH and NT rats became supersensitive to NE; the magnitude of supersensitivity in the two groups was comparable.Spontaneously hypertensive and NT rats were pithed and then tested for vascular responses to NE. Following pithing, the basal blood pressures of the two groups were similar, and so were NE responses. When animals had been previously sympathectomized with 6-OHDA, supersensitivity still developed. Moreover, the magnitude of supersensitivity in pithed, sympathectomized SH rats was nearly identical to that in pithed, sympathectomized NT rats.Pretreatment of animals with cocaine resulted in presynaptic supersensitivity. The magnitude of supersensilivity produced by cocaine was similar to that produced by chronic 6-OHDA treatment.These data are discussed in terms of the role that the sympathetic nervous system plays in the genesis and maintenance of spontaneous hypertension.