Chronic treatment with L-5-hydroxytryptophan prevents the development of DOCA-salt-induced hypertension in rats.

Abstract

Chronic subcutaneous (s.c.) infusion (osmotic minipump) of L-5-hydroxytryptophan (L-5-HTP, 4.2 to 12.6 mg/day) to uninephrectomized, deoxycorticosterone acetate-salt-treated (DOCA) rats (1.36 mg/kg per day via s.c. silastic implants) reduced their exaggerated intake of isotonic saline significantly (12.6 mg/day), prevented the elevation of blood pressure (4.2 to 12.6 mg/day), prevented cardiac hypertrophy (12.6 mg/day), and provided modest protection against reduction of urinary concentrating ability, characteristic of DOCA-treated rats during a 24-h dehydration. The exaggerated dipsogenic response of DOCA-treated rats to administration of angiotensin II (AII, 50 and 100 micrograms/kg, s.c.) was also reduced by treatment with L-5-HTP (4.2 and 8.4 mg/day). The specific binding of AII to its receptors in membranes from the diencephalon of the brain was increased significantly above control level by chronic treatment with DOCA, but was returned to control level by concomitant treatment with L-5-HTP. Daily urinary excretion of dopamine, increased by treatment with DOCA, was unaffected by treatment with L-5-HTP (6.3 mg/day). Daily urinary excretion of epinephrine was increased by treatment with L-5-HTP (6.3 and 12.6 mg/day). These results suggest that chronic administration of L-5-HTP provides significant protection against the development of DOCA-induced hypertension, polydipsia, polyuria, and cardiac hypertrophy in rats. The mechanism by which L-5-HTP protects is unclear and remains to be established.