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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Malnutrition is frequently associated with advanced cirrhosis. To investigate the role of portal hypertension in nutritional impairment, we developed an animal model to isolate and characterize the effects of chronic intestinal venous hypertension on intestinal nutrient absorption. We performed mesenteric arteriovenous anastomosis combined with portal vein banding in rats. Hepatic architecture and excretory function (bile flow and bile salt output) were unaltered, while severe and persistent intestinal venous hypertension was produced. We then measured in vivo absorption rates of three test nutrients (vitamin D3, valine, and tryptophan) and water. Vitamin D3 absorption was significantly impaired by intestinal congestion, while amino acid absorption was unaffected. Splanchnic hypertensive rats absorbed less water than controls. We conclude that chronic intestinal venous hypertension alone selectively impairs nutrient absorption.
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PMID:Selective impairment of nutrient absorption from intestines with chronic venous hypertension. 300 45

Chronic dietary administration of L-tryptophan (2.5 and 5.0 g/100 g food) to rats provided significant protection against the development of hypertension induced by bilateral encapsulation of the kidneys with latex envelopes. Lower doses of tryptophan (0.5 and 1.0 g/100 g food) attenuated the rate of elevation of blood pressure, but failed to maintain systolic blood pressures at levels significantly below that of untreated renal hypertensive controls. The body weight of the rats was not affected significantly by treatment with any dose of tryptophan used. Chronic treatment with tryptophan also protected against the reduced urinary concentrating ability during a 24-hour dehydration that characteristically accompanies renal encapsulation. 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.
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PMID:Effect of chronic dietary treatment with L-tryptophan on the development of renal hypertension in rats. 335 43

The present study investigated the metabolism of serotonin (5-HT) in rats made hypertensive by treatment with DOCA/NaCl. 5-Hydroxytryptamine and its major metabolite, 5-hydroxyindoleacetic acid (5-HIAA) were significantly elevated in a number of regions of the brain in rats treated for 2 weeks with DOCA/NaCl. Elevations in levels of 5-HIAA were present with 4 weeks of treatment with DOCA/NaCl but levels of 5-HT were not altered. No changes in the metabolism of 5-HT were detectable with 5 weeks of treatment with DOCA/NaCl. Levels of tryptophan were also elevated in a number of regions of the brain by treatment with DOCA/NaCl. Alterations in norepinephrine (NE) in the brainstem were present with 2, 4 or 5 weeks of treatment with DOCA/NaCl. The neurochemical effects of muscimol, a GABA agonist, were also investigated in rats treated with DOCA/NaCl for 4 weeks. Significant increases in levels of 5-HIAA and 5-HT were present in rats treated with DOCA/NaCl but not in controls, 15 min after intraventricular administration of muscimol (1.0 microgram/300 g body weight). Sixty min after muscimol, 5-HIAA was increased in both rats treated with DOCA/NaCl and control rats, but 5-HT was only increased in the hypothalamus. Treatment with DOCA/NaCl produced changes in the metabolism of 5-HT that may be important in the genesis of hypertension, but are not required for the maintenance of elevated arterial pressure. A disturbance of GABA-5-HT interactions between GABA and 5-HT in brainstem sites may also contribute to the pathogenesis of hypertension induced by DOCA/NaCl.
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PMID:Central serotonergic alterations in deoxycorticosterone acetate/NaCl (DOCA/NaCl)-induced hypertension. 341 40

Chronic dietary administration of either l-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.
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PMID:Effect of chronic dietary treatment with nicotinic acid on the development and maintenance of deoxycorticosterone-acetate-salt-induced hypertension. 342 Jan 63

Hypertension developed within 3 to 5 weeks in uninephrectomized rats administered deoxycorticosterone acetate (DOCA) at a dose of 850 micrograms X kg-1 X day-1 via Silastic tubes and given isotonic saline to drink. Chronic dietary administration of tryptophan (25 and 50 g/kg of food) to DOCA-treated rats reduced their exaggerated intake of NaCl solution and attenuated the elevation of 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 assessed the responsiveness to the beta-adrenergic agonist, isoproterenol. These included measurement of drinking and heart rate following acute administration of isoproterenol. The characteristically depressed drinking and chronotropic responses of DOCA-treated rats to acute administration of isoproterenol were unaffected by tryptophan. Responsiveness to angiotensin II (AII) was also tested by assessment of dipsogenic and metabolic responses to acute administration of AII. The increased drinking and tail skin temperature responses to administration of AII, characteristic of DOCA-treated rats, were reduced in a graded fashion by treatment with graded doses of tryptophan. The specific binding of AII to its receptors in membranes form the diencephalon of the brain was increased by treatment with DOCA but was returned to control level by concomitant treatment with tryptophan. The content of serotonin in the mesencephalon of the brain was not changed significantly by treatment with tryptophan, but the content of 5-hydroxyindole acetic acid in the same region increased significantly, suggesting that turnover of serotonin was increased by chronic treatment with tryptophan. The cardiac hypertrophy characteristic of treatment with DOCA was attenuated significantly by chronic treatment with tryptophan, while the low, resting plasma renin activity of the DOCA-treated group was unchanged. These results suggest that tryptophan provides significant protection against the development of DOCA-induced hypertension, polydipsia, polyuria, and cardiac hypertrophy in rats. It also reduces the hyperresponsiveness to treatment with AII, possibly by decreasing the specific binding of AII to its receptors. It also appears to increase the turnover of serotonin in the brain. Whether either one or all of these is responsible for the antihypertensive effect of tryptophan remains for further study.
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PMID:Chronic dietary administration of tryptophan prevents the development of deoxycorticosterone acetate salt induced hypertension in rats. 362 Oct 37

The structural and enzymatic aspects of renin are of great interest in hypertension research. In this paper, we examine the solution accessibility of the three tryptophan (Trp) residues of mouse submaxillary gland renin by solute collisional fluorescence quenching. Our studies indicate that there are two "classes" of Trp residues in renin: class I, a class of Trp residues which are at or near the surface of renin and fully accessible to the fluorescence quencher iodide; and class II, a class of Trp residues which are, for practical experimental conditions, totally inaccessible to the aqueous solution. The former class contains 2 Trp residues, while only a single Trp is identified in the latter class. The presence of a tetradecapeptide substrate or a nonhydrolyzable substrate analogue (peptide H-77) lowers the accessibility of iodide to the class I Trp residues. These data indicate that the class I Trp residues are at or near the peptide-binding site of renin. In addition, the finding that the class I Trp residues are quantitatively quenched more efficiently than the Trp model compound indole suggests that the environment of the class I tryptophans may be positively charged, and thus have a higher "local" concentration of iodide. These data, taken together with the available sequence and computer-generated three-dimensional structure of renin, permit us to speculate that the class I Trp residues are Trp-39 and Trp-300. This solution study of renin structure is discussed in light of the known information about renin catalysis and physiology.
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PMID:Probing the renin active site by collisional quenching of endogenous fluorescence. 390 89

Surgical reduction of renal mass in the rat leads to proteinuria, hypertension, and progressive renal failure beyond that of the original physical destruction of renal mass. Both hypertension and proteinuria have been implicated in the process of progression of renal failure. The seven/eighths nephrectomized rats fed a diet supplemented with 4% tryptophan (UT) had a urinary albumin excretion rate of 0.055 +/- 0.056 mg/100 g body weight/hr compared to 0.02 +/- 0.029 mg/100 g body weight/hr in control rats, whereas the nephrectomized rats fed a regular diet (UR) excreted 1.12 +/- 0.730 mg/100 g body weight/hr (P less than 0.001). Hypertension was also prevented in the UT group but not in the UR group. Once hypertension and proteinuria were established during maintenance on a regular diet, they were not reversed by subsequent dietary tryptophan supplementation. If dietary tryptophan supplementation is continued, however, the progressive histopathology that develops after seven-eighths nephrectomy is not prevented despite avoidance of proteinuria and hypertension.
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PMID:Dietary tryptophan supplementation prevents proteinuria in the seven-eighths nephrectomized rat. 684 66

Vascular responsiveness to 5-hydroxytryptamine (5-HT) is dramatically increased in hypertension. The hypothesis that augmented vasoconstriction to 5-HT in hypertension is due to a change in receptor subtype on vascular myocytes was tested. Mesenteric arteries from deoxycorticosterone acetate (DOCA)-salt hypertensive (systolic blood pressure > 180 mm Hg) and sham normotensive (systolic blood pressure < 130 mm Hg) rats were mounted in isolated tissue baths for measurement of isometric contractile force. The receptor mediating contraction in isolated mesenteric arteries from sham and DOCA-salt hypertensive rats is a member of the 5-HT2 family based on rank order of agonist potency (5-HT = alpha-methyl-5-HT [5-HT2 receptor agonist]>tryptamine>5-hydroxykynuramine). 5-HT was approximately 10-fold more potent in contracting mesenteric arteries from DOCA-salt hypertensive rats compared with arteries from sham normotensive rats. The tryptophan metabolite kynuramine, which possesses significant contractile activity at the 5-HT2B receptor, contracted hypertensive arteries significantly (50% of 5-HT maximum) but not sham arteries. Ketanserin (5-HT2A antagonist) competitively inhibited contraction to 5-HT in arteries from normotensive rats (-log dissociation constant [mol/L]; pKB = 8.54) but not from hypertensive rats (pKB > 6.5). Moreover, contraction to kynuramine was not blocked by ketanserin. Thus, under normal conditions, 5-HT2A receptors mediate contraction to 5-HT. However, in DOCA-salt hypertension, ketanserin-insensitive 5-HT2 receptors, possibly 5-HT2B receptors, mediate mesenteric arterial contraction to 5-HT.
Hypertension 1995 Dec
PMID:5-Hydroxytryptamine2B receptor mediates contraction in the mesenteric artery of mineralocorticoid hypertensive rats. 749 67

Chronic dietary administration of pyridoxine HCl (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 micrograms/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.
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PMID:Effect of pyridoxine and tryptophan, alone and combined, on the development of deoxycorticosterone acetate-induced hypertension in rats. 766 91

Bioreactor systems have been developed for the production of ajmalicine, an alkaloid used in the treatment of hypertension. Cell cultures of Catharanthus roseus produced higher levels of ajmalicine (323 micrograms g-1 dry weight) in a production medium enriched with tryptophan. The cell cultures were grown in medium prepared in tap water and market sugar with a view to minimise the costs of production. Large-scale cultivation of cell suspension was performed in a 20-l airlift bioreactor under controlled conditions. An ajmalicine production of 315 micrograms g-1 dry weight was achieved in the bioreactor after 14 d of cultivation.
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PMID:Large-scale cultivation of Catharanthus roseus cells: production of ajmalicine in a 20-l airlift bioreactor. 776 26


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