Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tetrahydrobiopterin is one of the most potent naturally occurring reducing agents and an essential cofactor required for enzymatic activity of nitric oxide synthase (NOS). The exact role of tetrahydrobiopterin in the control of NOS catalytic activity is not completely understood. Existing evidence suggests that it can act as allosteric and redox cofactors. Suboptimal concentration of tetrahydrobiopterin reduces formation of nitric oxide and favors "uncoupling" of NOS leading to NOS-mediated reduction of oxygen and formation of superoxide anions and hydrogen peroxide. Recent findings suggest that accelerated catabolism of tetrahydrobiopterin in arteries exposed to oxidative stress may contribute to pathogenesis of endothelial dysfunction present in arteries exposed to hypertension, hypercholesterolemia, diabetes, smoking, and ischemia-reperfusion. Beneficial effects of acute and chronic tetrahydrobiopterin supplementation on endothelial function have been reported in experimental animals and humans. Furthermore, it appears that beneficial effects of some antioxidants (e.g., vitamin C) on vascular function could be mediated via increased intracellular concentration of tetrahydrobiopterin. In this review, the potential role of tetrahydrobiopterin in the pathogenesis of vascular endothelial dysfunction and mechanisms underlying beneficial vascular effects of tetrahydrobiopterin will be discussed.
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PMID:Vascular endothelial dysfunction: does tetrahydrobiopterin play a role? 1151 62

Scurvy has been known since ancient times, but the discovery of the link between the dietary deficiency of ascorbic acid and scurvy has dramatically reduced its incidence over the past half-century. Sporadic reports of scurvy still occur, primarily in elderly, isolated individuals with alcoholism. The incidence of scurvy in the pediatric population is very uncommon, and it is usually seen in children with severely restricted diets attributable to psychiatric or developmental problems. The condition is characterized by perifollicular petechiae and bruising, gingival inflammation and bleeding, and, in children, bone disease. We describe a case of scurvy in a 9-year-old developmentally delayed girl who had a diet markedly deficient in vitamin C resulting from extremely limited food preferences. She presented with debilitating bone pain, inflammatory gingival disease, perifollicular hyperkeratosis, and purpura. Severe hypertension without another apparent secondary cause was also present, which has been previously undescribed. The signs of scurvy and hypertension resolved after treatment with vitamin C. The diagnosis of scurvy is made on clinical and radiographic grounds, and may be supported by finding reduced levels of vitamin C in serum or buffy-coat leukocytes. The response to vitamin C is dramatic. Clinicians should be aware of this potentially fatal but easily curable condition that is still occasionally encountered among children.
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PMID:An orange a day keeps the doctor away: scurvy in the year 2000. 1153 73

Ascorbic acid (vitamin C) and alpha-tocopherol (vitamin E) have antioxidant properties that could improve redox-sensitive vascular changes associated with hypertension. We determined whether vitamins C and E influence vascular function and structure in hypertension by modulating activity of NADPH oxidase and superoxide dismutase (SOD). Adult stroke-prone spontaneously hypertensive rats (SHRSP) were divided into 3 groups: control (C; n=6), vitamin C-treated (vit C, 1000 mg/day; n=7), and vitamin E-treated (vit E, 1000 IU/day; n=8). All rats were fed 4% NaCl. Blood pressure was measured weekly. After 6 weeks of treatment, the rats were killed, and mesenteric arteries were mounted as pressurized preparations. Vascular O(2)(-) generation and NADPH oxidase activity were measured by chemiluminescence. Vascular SOD activity and plasma total antioxidant status (TAS) were determined spectrophotometrically. Blood pressure increased from 212+/-7 to 265+/-6 mm Hg in controls. Treatment prevented progression of hypertension (vit C, 222+/-6 to 234+/-14 mm Hg; vit E, 220+/-9 to 227+/-10 mm Hg). Acetylcholine-induced vasodilation was improved (P<0.05), and media-to-lumen ratio was reduced (P<0.05) in the treated rats. O(2)(-) was lower in vitamin-treated groups compared with controls (vit C, 10+/-4 nmol. min(-1). g(-1) dry tissue weight; vit E, 9.6+/-3.5 nmol. min(-1). g(-1) dry tissue weight; C, 21+/-9 nmol. min(-1). g(-1) dry tissue weight; P<0.05). Both vitamin-treated groups showed significant improvement (P<0.01) in TAS. These effects were associated with decreased activation of vascular NADPH oxidase (vit C, 46+/-10; vit E, 50+/-9; C, 70+/-16 nmol. min(-1). g(-1) dry tissue weight, P<0.05) and increased activation of SOD (vit C, 12+/-2; vit E, 8+/-1; C, 4.6+/-1 U/mg; P<0.05). Our results demonstrate that vitamins C and E reduce oxidative stress, improve vascular function and structure, and prevent progression of hypertension in SHRSP. These effects may be mediated via modulation of enzyme systems that generate free radicals.
Hypertension 2001 Sep
PMID:Antioxidant effects of vitamins C and E are associated with altered activation of vascular NADPH oxidase and superoxide dismutase in stroke-prone SHR. 1156 40

It has been shown that BH(4) ameliorates endothelial dysfunction associated with conditions such as hypertension, cigarette smoking, and diabetes. This effect has been proposed to be due to a superoxide scavenging activity of BH(4). To examine this possibility we determined the rate constant for the reaction between BH(4) and superoxide using electron paramagnetic resonance (EPR) spin trapping competition experiments with 5-diethoxyphosphoryl-5-methyl-1-pyrroline N-oxide (DEPMPO). We calculated a rate constant for the reaction between BH(4) and superoxide of 3.9 +/- 0.2 x 10(5) M(-1)s(-1) at pH 7.4 and room temperature. This result suggests that superoxide scavenging by BH(4) is not a major reaction in vivo. HPLC product analysis showed that 7,8-BH(2) and pterin are the stable products generated from the reaction. The formation of BH(4) cation radical (BH(4)(*+)) was demonstrated by direct EPR only under acidic conditions. Isotopic substitution experiments demonstrated that the BH(4)(*+) is mainly delocalized on the pyrazine ring of BH(4). In parallel experiments, we investigated the effect of ascorbate on 7,8-BH(2) reduction and eNOS activity. We demonstrated that ascorbate does not reduce 7,8-BH(2) to BH(4), nor does it stimulate nitric oxide release from eNOS incubated with 7,8-BH(2). In conclusion, it is likely that BH(4)-dependent inhibition of superoxide formation from eNOS is the mechanism that better explains the antioxidant effects of BH(4) in the vasculature.
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PMID:Reaction of tetrahydrobiopterin with superoxide: EPR-kinetic analysis and characterization of the pteridine radical. 1159 82

Low-level lead exposure is a known cause of hypertension that has been associated with increased reactive oxygen species activity and endothelial-dependent vasorelaxation impairment. The effect of lead exposure on the vascular nitric oxide (NO)/cyclic guanocine monophosphate (cGMP) system was analyzed. Wistar rats were exposed to 5 ppm lead acetate in the drinking water during 30 d. Mean arterial BP increased significantly in the lead-treated rats. Relaxation to both acetylcholine and sodium nitroprusside (SNP) was reduced in lead-treated rats; however, the vascular wall of lead-administered rats showed an increased expression of endothelial NO synthase. The expression of both subunits (alpha(1) and beta(1)) of soluble guanylate cyclase (sGC) and the cGMP accumulated in the vascular wall were decreased in lead-treated rats. Cotreatment of lead with vitamin C (3 mmol/L) prevented the increase on mean arterial BP, improved the relaxation to both acetylcholine and sodium nitroprusside, and restored the normal expression of endothelial NO synthase and sGC proteins in the vascular wall. In conclusion, lead exposure altered both the endothelium-dependent and -independent relaxing response and induced a reduced expression of sGC in the vascular wall. These effects were abrogated with the antioxidant vitamin C, which suggests the involvement of reactive oxygen species in the regulation of the NO/cGMP relaxing system in the vascular wall of lead-treated rats.
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PMID:Alteration of the soluble guanylate cyclase system in the vascular wall of lead-induced hypertension in rats. 1172 27

Heart failure is characterized by neurohumoral alterations, such as activation of the sympathetic nervous system, stimulation of the renin-angiotensin system, increased activity of the endothelin system, increased production of norepinephrine, and increased circulating levels of cytokines. Oxidative stress is associated with the formation of reactive oxygen species (ROS). The myocardium has enzymes that stimulate ROS generation and enzymes with antioxidant effects. Several studies have suggested that ROS are increased in the failing heart. ROS may contribute to the pathophysiology of heart failure by initiating myocyte apoptosis and exerting direct negatively inotropic effects through the reduction of cytosolic intracellular free calcium. However, mechanisms such as endothelial dysfunction and inflammation have also been involved in the progression of heart failure. Antioxidants (eg, vitamin C) seem to improve endothelial functionality and reduce the inflammatory response in patients with heart failure. Therefore, in this review, we analyzed the involvement of ROS in the cellular and molecular mechanisms associated with endothelial dysfunction in heart failure.
Hypertension 2001 Dec 01
PMID:Heart failure, redox alterations, and endothelial dysfunction. 1175 25

Patients with essential hypertension have an impaired endothelium-dependent vascular relaxation in the renal arteries. The possible mechanisms by which essential hypertension is associated with alterations in endothelial function are decreased endothelial nitric oxide (NO) synthase activity, decreased availability or deficiency of L-arginine, increased endogenous NO synthase inhibitor, inactivation of NO by superoxide anions, and increased vasoconstrictors. However, the precise mechanism is not known. In addition, we are now confronted with a difficult question. And the question is whether endothelial dysfunction is a cause or consequence of hypertension. We hypothesize that the initial endothelial dysfunction raises blood pressure, and the development of hypertension impairs much more endothelial function, resulting in constituting the vicious cycle between endothelial dysfunction and hypertension. However, at the moment, it is impossible to answer this question with any certainty. Impairment of endothelial function has been shown to play a critical role in the development and maintenance of hypertension. It is clinically important to select an appropriate intervention that is effective in improving endothelial dysfunction in patients with essential hypertension. Several investigators including us have demonstrated that certain interventions improve endothelial dysfunction of forearm and renal circulation in patients with essential hypertension: angiotensin-converting enzyme inhibitors; lifestyle modification: exercise, body weight reduction, and sodium reduction; estrogen replacement in postmenopausal women; and novel properties: vitamin C and tetrahydrobiopterine. In patients with essential hypertension, endothelial function is impaired in several arteries. However, endothelial dysfunction in essential hypertension is reversible. We can restore endothelial function in essential hypertensive patients.
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PMID:Renal endothelial dysfunction and hypertension. 1187 76

Accumulated evidence from experimental and epidemiological studies indicates that there is a low risk of degenerative diseases, cardiovascular disease, hypertension, cataract, stroke and, in particular, cancers in people with a high intake of fruit and vegetables. This protective effect is assumed to be associated mainly with the antioxidant activities of either individual or interacting bioactive components present in the fruits and vegetables, and with other biochemical and physical characteristics of the identified and unknown bioactive components. The implicated bioactive components present in citrus fruits include vitamin C, beta-carotene, flavonoids, limonoids, folic acid, and dietary fibre. A high intake of citrus fruits may reduce the risk of degenerative diseases.
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PMID:Anticancer and health protective properties of citrus fruit components. 1189 Jun 43

A large controlled study supported by the NIH, the DASH study (Dietary Approaches to Stop Hypertension), demonstrated that a diet rich in fruits and vegetables can reduce blood pressure in persons with moderate elevation in blood pressure (BP). Fruits and vegetables are important sources of antioxidants such as vitamin C and carotenoids. We conducted a study in which we fed people a diet deficient in vitamin C for 30 days, followed for another 30 days by a diet adequate in vitamin C. Their blood levels of vitamin C and blood pressure (BP) were tracked. Plasma vitamin C was inversely related to diastolic blood pressure one month later (correlation = -0.48, P < 0.0001). Persons whose blood levels of vitamin C went down the furthest on depletion had the highest blood pressure one month later. Persons in the lowest one-fourth of the plasma vitamin C distribution had diastolic BP 7 mm Hg higher than did those in the upper one-fourth of the plasma ascorbic acid distribution. Multivariate control for age, body mass index, other plasma antioxidants, and dietary energy, calcium, fiber, sodium, and potassium did not reduce the plasma vitamin C effect. We believe that this indicates that the tissue stores of vitamin C may be important in regulating blood pressure. It is often thought that Americans' intake of vitamin C is ample, since the average intake is about 100 mg/day. However, this average level obscures the fact that substantial numbers of people actually have habitually low intake levels and low blood levels. African Americans tend to have low blood levels of vitamin C as well as the highest risk of hypertension. Low intake of antioxidant-rich fruits and vegetables may be one of the causes of hypertension.
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PMID:Ascorbic acid, blood pressure, and the American diet. 1197 95

Relationships of nutrients, alcohol intake, and change in weight to change in blood pressure over 8 years in 1714 employed middle-aged men from the Chicago Western Electric Study were explored. At first and second annual examinations, 2 in-depth interviews were performed to assess usual intake of foods and beverages during the preceding 28 days. Annual follow-up data through examination year 9 were used to determine change in weight and blood pressure. Averages of nutrients from 2 interviews were related to annual blood pressure change from baseline by use of the Generalized Estimating Equation, with control for confounders. In analyses of dietary variables considered individually, total and animal protein; total, saturated, monounsaturated, and polyunsaturated fatty acids; cholesterol; Keys dietary lipid score; calcium; alcohol; and average annual change in weight were positively and significantly related to average annual change in systolic pressure; vegetable protein, total carbohydrate, beta-carotene, and an antioxidant vitamin score based on vitamin C and beta-carotene were inversely and significantly related to average annual change in systolic pressure. In analyses of combinations of dietary factors, cholesterol, Keys score, and alcohol were positively related to change in systolic pressure (eg, Z-scores 2.21, 2.05, and 2.50); vegetable protein and antioxidant index were inversely related to change in systolic and diastolic pressure. Change in weight was directly related to change in systolic and diastolic pressure. These findings support the concept that multiple macro- and micronutrients, alcohol intake, and calorie imbalance relate prospectively to blood pressure change.
Hypertension 2002 May
PMID:Eight-year blood pressure change in middle-aged men: relationship to multiple nutrients. 1201 83


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