Effect of Chronic Dietary Treatment with Nicotinic Acid on the Development and Maintenance of Deoxycorticosterone-Acetate-Salt-Induced Hypertension

Abstract

Chronic dietary administration of either /-tryptophan (5.0%) or nicotinic acid (5.0%) reduced the elevated blood pressure of rats with established, deoxycorticosterone-acetate (DOCA)-salt-induced hypertension without affecting either body weight or cardiac hypertrophy. In a second study, chronic dietary administration of nicotinic acid (2.5 and 5.0%) provided significant protection against the development of an elevated blood pressure in rats treated with DOCA salt. A modest (approximately 10 %) reduction in cardiac hypertrophy was also observed in the two nicotinic-acid-treated groups. Treatment with either dose of nicotinic acid did not, however, prevent either the renal hypertrophy characteristic of DOCA-salt-induced hypertension in rats or their reduced renal concentrating ability during a 24-hour dehydration; nor did treatment with nicotinic acid reduce the excessive ingestion of saline characteristic of chronic treatment with DOCA. In contrast, treatment with the higher dose of nicotinic acid prevented the excessive loss of sodium into urine characteristic of DOCA-salt-induced hypertension when the rats were loaded (3% of body weight, i.p.) with a hypotonic (0.075 M) saline solution. These results suggest that increased production of nicotinic acid resulting from dietary administration of tryptophan may play a role in the protective effect of tryptophan against the development of DOCA-salt-induced hypertension. These studies do not, however, provide a mechanism by which nicotinic acid may manifest its beneficial effects.

Reduction in the Elevated Blood Pressure of Dahl Salt-Sensitive Rats Treated Chronically with L-5-Hydroxytryptophan

“…5-HTP is the immediate precursor of 5-HT and is con verted directly to 5-HT. However, trypto phan may exert its anthypertensive effects by conversion both to serotonin and to other metabolites like nicotinic acid and indole-3-pyruvic acid, both of which were shown to have an antihypertensive effect in rats treated chronically with DOCA [15,28], Re peated administration of indole-3-pyruvic acid, a tryptophan keto analogue contained in biological fluids, by oral gavage signifi cantly decreased systolic blood pressure in spontaneously hypertensive, DOCA-induced hypertensive, and Grollman hypertensive rats [28].…”

“…It could be related to an increased production and turnover of serotonin initiated by an excessive availabil ity of substrate [29], but it may also be related to an excessive production of one or several of the metabolites of tryptophan [ 18], Thus, nicotinic acid [15] and indole-3-pyruvic acid [28], both metabolites of trypto phan, are reported to have antihypertensive effects in hypertensive rats. To bypass the latter possibility, L-5-hydroxytryptophan (5-HTP), the immediate precursor of serotonin, was administered to DOCA-treated rats in an earlier study from this laboratory and was shown to prevent both the elevation of blood pressure and cardiac hypertrophy.…”

Effect of Chronic Dietary Treatment with Z-Tryptophan on the Development of Cold-Induced Hypertension in Rats

“…These include DOCA-induced [1,3], renal-induced [2], spontaneous [4] and Dahl salt-induced hy pertensions [5]. In addition, metabolites of L-tryptophan were shown to have antihyper tensive effects, supporting the hypothesis that L-tryptophan may exert its antihyper tensive effects either by conversion to 5-hydroxytryptamine (serotonin) [8] or by con version to other metabolites like nicotinic acid [24] and indole-3-pyruvic acid [25]. Both of the latter compounds were shown to have antihypertensive effects in rats.…”

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

“…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.…”