Prevention of Doca‐induced Hypertension in Rats by Chronic Treatment With Tryptophan

Abstract

Hypertension developed within 5 weeks in uninephrectomized rats administered deoxycorticosterone acetate (DOCA, 30 mg/kg, s.c., weekly) and given isotonic saline to drink. Chronic dietary administration of tryptophan (50 g/kg food) reduced intake of saline solution and prevented the elevation of systolic blood pressure induced by treatment with DOCA alone. Treatment with tryptophan also protected against the reduction in urinary concentrating ability during a 24 h dehydration that is characteristic of DOCA-treated rats. Other tests were carried out to assess the responsiveness to the beta-adrenergic agonist, isoproterenol. The tests included measurement of drinking and heart rate following acute administration of isoproterenol. The characteristically depressed drinking response of DOCA-treated rats to acute administration of isoproterenol was returned to that of untreated controls by chronic treatment with tryptophan. However, the reduced chronotropic response of the heart of DOCA-treated rats to administration of isoproterenol was unaffected. The cardiac hypertrophy characteristic of DOCA-treatment was attenuated significantly by chronic treatment with tryptophan. These results suggest that tryptophan provides significant protection against the development of DOCA-induced hypertension, polydipsia, and cardiac hypertrophy in rats. The mechanism by which tryptophan protects is unknown and requires additional study.

Effect of Chronic Dietary Treatment with L-Tryptophan on the Development of Renal Hypertension in Rats

“…In the earlier studies in which tryptophan was administered to DOCA-salt-treated rats, a return of their exaggerated NaCl intake toward control level was observed [9,11], It was postulated that the reduction in NaCl intake may have contributed to the antihy pertensive activity of tryptophan [ 11 ]. In the present experiments, the rats received water rather than saline as their sole drinking solu tion.…”

“…While this effect is small, it must be considered in the context that the extent of cardiac hypertrophy in the un treated renal encapsulated group was about 16% (table III). Further, the extent of protec tion against the development of renal hyper tension by tryptophan was less than that observed in DOCA-treated rats [9,11 ].…”

“…A modest (5-8%) effect of treatment to reduce cardiac hypertrophy was also observed. The mechanism of the antihypertensive effect of tryptophan is not revealed by these studies although they rule out the possibilities that reduction in sodium intake and/or reduction in body weight may be important factors.Earlier studies from this laboratory have shown that chronic dietary administration of L-tryptophan prevented the development of hypertension, polydipsia, polyuria, and car diac hypertrophy accompanying chronic treatment of rats with deoxycorticosterone acetate (DOCA) [9,11], In addition, chronic dietary treatment with tryptophan increased the turnover of serotonin in the mesencepha lon of DOCA-treated rats, and attenuated the DOCA-induced increase in specific binding of angiotensin II (All) to its receptors in the diencephalon. Thus, many potential mecha nisms present themselves as possible expla nations for the antihypertensive effect of treatment with tryptophan.…”

Effect of Pyridoxine and Tryptophan, Alone and Combined, on the Development of Deoxycorticosterone Acetate-Induced Hypertension in Rats

“…The significant interac tion of these two compounds in attenuating the elevation of blood pressure, mentioned above, suggests that the mechanisms involved are different, such that the combination of the two drugs results in greater responses than would be expected from the summation of the two individual responses. Additional studies from this and other lab oratories have shown that chronic treatment with tryptophan protects against the develop ment of DOCA-induced, Dahl salt-sensitive, spontaneously induced, renal-induced, and cold-induced hypertensions in rats [1][2][3][4][9][10][11][12][13]. In addition, chronic administration of tryptophan to humans with borderline essen tial hypertension has been shown to reduce blood pressure [14,15].…”

“…The results of this study suggest that pyridoxal phosphate can also lower the blood pressure of rats with established hypertension. Thus, these studies reveal that pyridoxine, pyridoxal phosphate and tryptophan are potential antihypertensive agents.Earlier studies from this laboratory showed that chronic dietary administration of trypto phan prevented the development of deoxy corticosterone acetate (DOCA)-induced hy pertension in rats [1,2], These studies also showed that the efficacy of tryptophan in pre venting the development of DOCA-induced Received: September 16, 1994 Accepted: November 25, 1994 hypertension was enhanced by its combina tion with nicotinic acid [3,4], Since pyridox ine (or vitamin B6) is an important cofactor at a number of the steps in the metabolic path ways for tryptophan ( fig. 7), it seemed likely that tryptophan could be maximally effective in preventing the development of DOCADr.…”