Antihypertensive Activity of Indolepyruvic Acid

Rats of the Dahl salt-sensitive (DS) and Dahl salt-resistant (DR) strains were placed on a 4% NaCl diet and blood pressures were monitored. Chronic subcutaneous infusion of L-5-hydroxytryptophan (L-5-HTP, 12.6 mg/day) by osmotic minipumps significantly decreased the elevated systolic blood pressure of DS rats on a 4% NaCl diet. Blood pressures of DR rats were unaffected by treatment with L-5-HTP. Cardiac hypertrophy was associated with Dahl salt-induced hypertension. However, treatment with L-5-HTP failed to reduce the weight of the heart significantly. These results suggest that chronic administration of L-5-HTP was effective in reducing the elevated blood pressure in the DS model. The specific mechanisms by which L-5-HTP reduces the elevated blood pressure in DS rats is not clear and remains for further study.

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Baron

Riesselmann²,

Fregly³

1991

“…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.…”

Section: Discussionmentioning

confidence: 88%

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

Riesselmann

Baron²,

Fregly³

et al. 1991

This study was designed to assess the effect of chronic dietary administration (2.5 and 5.0% by weight) of the neutral amino acid, L-tryptophan, on the development of hypertension during chronic exposure to cold. In addition, a warm-adapted and cold-treated control group receiving unsupplemented food were used. Chronic administration of the lower dose of L-tryptophan (850 mg/day) prevented the elevation of blood pressure attenuated cardiac hypertrophy, and had no effect on body weight during exposure to cold. The higher dose of L-tryptophan (1,690 mg/day) attenuated the rate of blood pressure increase, did not affect cardiac hypertrophy, attenuated the gain in body weight, and increased the urinary output of epinephrine. Thus, this dose may be associated with some toxicity. Both doses of tryptophan failed to prevent certain other responses characteristically occurring during exposure to cold: i.e. increased weight of the kidneys, adrenal glands and brown adipose tissue; increased food and water consumption; increased dipsogenic responsiveness to angiotensin II, and increased plasma aldosterone concentration. The results indicate that chronic dietary administration of L-tryptophan (850 mg/day) can prevent the development of cold-induced hypertension, as it can in all other models of hypertension tested thus far in rats.

“…7). Recently, Squadrito et al [ 17] reported that chronic ( 10-day) administration of indole-3-pyruvic acid (100 mg/kg/day, orally) to spontaneously hy pertensive, DOCA plus salt hypertensive, and Grollman-type renal hypertensive rats re duced blood pressure. However, this dose had no significant effect on the blood pressure of normotensive controls.…”

Section: Discussionmentioning

confidence: 99%

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

Fregly

Cade²

1995

Chronic dietary administration of pyridoxine HC1 (300 mg/kg/day), L-tryptophan (1.26 g/kg/day), or a combination of the two can attenuate the elevation of systolic blood pressure in DOCA-salt-treated rats. With these treatments, the characteristic increase in the weight of the heart accompanying chronic administration of DOCA (786 µg/kg/day) was also attenuated. Thus, both tryptophan and pyridoxine possess antihypertensive properties, and the combination of the two appeared to provide greater protection than either alone. The results are consistent with the possibility that pyridoxine, an important cofactor in the metabolic pathways for tryptophan, may facilitate the conversion of tryptophan to antihypertensive compounds. Additional studies will be required to determine which of the metabolites of tryptophan possess antihypertensive properties. Pyridoxal phosphate, one of the metabolites of pyridoxine, was also administered chronically in the diet (1.0 and 2.0% by weight) to rats whose blood pressures were elevated by administration of DOCA. 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.