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Query: UMLS:C0085580 (essential hypertension)
 14,686 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Coenzyme Q10 has been administered to five patients having essential hypertension and deficiencies of activity of succinate dehydrogenase-co-enzyme Q10 reductase in leucocyte preparations ranging from 20-40%. For a 74-year old male, the systolic pressure was reduced (p less than 0.001), the diastolic pressure was reduced (p less than 0.05), the specific activity of the coenzyme Q10-enzyme was increased (p less than 0.001), and the deficiency of coenzyme Q10 activity was negated (p less than 0.01). Four patients receiving CoQ10 for 3-5 months showed reductions (p less than 0.05 to p less than 0.001) of diastolic pressure, and 3 of these 4 showed reductions (p less than 0.05 to p less than 0.01) of diastolic pressure. Initial deficiencies of enzyme activity were reduced (p less than 0.01 to 0.05) in two patients. Three other patients did not show the high level of deficiency on treatment as initially observed. These effects of CoQ10 on the reduction of systolic and diastolic blood pressures, increase in CoQ10-enzyme activity, and reduction of CoQ10-deficiency are presumably due to improved bioenergetics through correction of a deficiency of coenzyme Q10.
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PMID:Bioenergetics in clinical medicine. VIII. Adminstration of coenzyme Q10 to patients with essential hypertension. 78 64

Results of our previous studies revealed a derangement in the peripheral metabolism of adrenal steroids in patients with essential hypertension. To investigate further this finding, all indIVidual free and conjugated metabolites of cortisol were isolated, identified and quantitated in plasma of 14 normotensive subjects and 13 patients with benign, uncomplicated essential hypertension, following iv administration of a tracer dose of [4-14-C] cortisol. In addition, plasma levels of endogenous cortisol were determined at 8 AM and 4 PM in all the subjects examined. The results obtained revealed the following statistically significant differences between normotensives and hypertensives: 1) Mean plasma concentrations of cortisol metabolites reduced in ring-A with nonreduced 20-ketone, tetrahydrocortisol, tetrahydrocortisone, and their 5alpha-epimers, were 30% lower in the hypertensives; since these steroids constitute the bulk of the major group of cortisol metabolites--the glucuronide conjugates, plasma levels of this group of conjugates measured in toto were also found to be significantly lower in the hypertensives. 2) Concentrations of cortisol metabolites with non-reduced ring-A (delta-4-3-keto configuration preserved) but with reduced 20-ketone and/or hydroxylated at C-6, 20alpha- and 20beta- dihydrocortisol, 6alpha- and 6beta-hydroxycortisol, and 6-hydroxy-20-dihydrocortisol (all 4 isomers), were 73%, 48% and 68% respectively, higher in the hypertensives; since these steroids constitute the bulk of the sulfate-conjugated and nucleoside-complexed metabolites of cortisol, plasma levels of these groups of metabolites, measured in toto, were also found to be higher in the hypertensives. No significant difference was found between normotensives and hypertensives in the AM and PM plasma levels of cortisol. These findings, in conjunction with the results of our studies on urinary corticosteroid metabolites, which yielded identical findings, provide evidence for a decreased activity of hepatic cortisol-delta-4-hydrogenase enzyme system and increased activities (presumably compensatorily) of cortisol-20-reductase and 6-hydroxylase enzyme systems in patients with essential hypertension. The interrelation of these findings with those of other investigators studying steroid metabolites in hypertension, points to the corticosteroid metabolizing enzymes may be an etiological factor in essential hypertension.
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PMID:Corticosteroids in human blood. VIII. Cortisol metabolites in plasma of normotensive subjects and patients with essential hypertension. 113 61

The specific activities (S.A.) of the succinate dehydrogenase-coenzyme Q10 (CoQ10) reductase of a control group of 65 Japanese adults and 59 patients having essential hypertension were determined. The mean S.A. of the hypertensive group was significantly lower (p less than 0.001) and the mean % deficiency of enzyme activity was significantly higher (p less than 0.001) than the values for the control group. These data on Japanese in Osaka agree with data on Americans in Dallas. Some patients showed no CoQ10-deficiency, and others showed definite deficiencies. Emphasizing the CoQ10-enzyme for patient selection, CoQ10 was administered to hypertensive patients. Four individuals showed significant but partial reductions of blood pressure. Monitoring the CoQ10-enzyme before, during, and after administration of CoQ10 indicated responses. The maintenance of high blood pressure could be primarily due to contraction of the arterial wall. Contraction or relaxation of an arterial wall is dependent upon bioenergetics, which also provide the energy for biosynthesis of angiotensin II, renin, aldosterone, and the energy for sodium and potassium transport. A clinical benefit from administration of CoQ10 to patients with essential hypertension could be based upon correcting a deficiency in bioenergetics, and point to possible combination treatments with a form of CoQ and anti-hypertensive drugs.
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PMID:Bioenergetics in clinical medicine. Studies on coenzyme Q10 and essential hypertension. 115 73

Increased cellular Na+/H+ antiport activity has been documented in various cell types from hypertensive humans and rats. This membrane abnormality may be associated with the thickening of the vascular media of resistance vessels. Such an abnormality has also been demonstrated in cells from type I diabetic patients with nephropathy, and may indicate the predisposition to essential hypertension in such patients. We now demonstrate the importance of the rate-limiting enzyme for cholesterol and isoprenoid synthesis, 3-hydroxy-3-methyl-glutaryl coenzyme A reductase, in determining cellular Na+/H+ antiport activity. This finding may have application in the future treatment of diabetic patients with proteinuria.
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PMID:Lipids and cellular Na+/H+ antiport activity in diabetic nephropathy. 132 9

11 beta-OHSD is an enzyme complex consisting of 11 beta-DH, converting cortisol to cortisone in man and an 11-keto-reductase performing the reverse reaction. Congenital deficiency of 11 beta-DH should be considered in any child presenting with mineralocorticoid hypertension and suppression of the renin-angiotensin-aldosterone axis. The keystone to diagnosis is the demonstration of a reduced daily production rate of cortisol and an increase in its plasma half-life. In the majority of cases diagnosis can be made from a urinary steroid metabolite profile indicating a high excretion of cortisol relative to cortisone metabolites. Cortisol is the responsible mineralocorticoid, and as such treatment with the pure glucocorticoid dexamethasone will prevent life-threatening hypokalemia, although additional anti-hypertensive drugs are usually required to control blood pressure. Liquorice and carbenoxolone, for years thought to be direct "agonists" of the mineralocorticoid receptor, in fact cause sodium retention through inhibition of 11 beta-DH. The demonstration of 11 beta-DH activity in the vasculature raises the possibility that it locally modules access of glucocorticoids to mineralocorticoid and possibly glucocorticoid receptors in the vessel wall. It remains possible that subtle alterations of this cortisol-cortisone shuttle are responsible for other forms of hypertension which are currently classified under the umbrella diagnosis of essential hypertension.
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PMID:The cortisol-cortisone shuttle and hypertension. 195 52

Recent pharmacological studies confirmed the role of hypercholesterolemia in the pathogenesis of coronary atherosclerosis. A 10% reduction in cholesterol levels can reduce the risk of coronary heart disease by 15%. However many hypercholesterolemic patients often suffer from arterial hypertension and drugs such as thiazide diuretics cause an imbalance in lipid metabolism. The efficacy and the tolerability of simvastatin (a inhibitor of HGM-CoA reductase) with that of gemfibrozil (a fibric acid derivative, which can reduce the VLDL level) were compared in a placebo-controlled study in 2 groups of patients with primary hypercholesterolemia and mild-to-moderate essential hypertension treated with hydrochlorothiazide. After 10 weeks standard hypolipidemic diet and hydrochlorothiazide (25 mg od) therapy, 30 patients whose cholesterol levels were still greater than or equal to 250 mg/100 ml and whose diastolic blood pressure was less than 95 mmHg were randomized to one of the following treatments: simvastatin, 20 mg od, gemfibrozil, 600 mg bid or placebo, while continuing dietetic and diuretic treatment. After 24 weeks treatment, simvastatin induced a 37% reduction in cholesterol plasma levels, a 9% increase of HDL and a 16% reduction of LDL. APO-A1 showed a 4% increase, while APO-B showed a 3% reduction. Gemfibrozil induced a 20% reduction in plasma triglycerides and a 13% decrease in plasma cholesterol, with a significant 19% increase in HDL and a 11% reduction in LDL. No significant variations in any of the lipid parameters monitored were observed in the placebo group. Treatment with simvastatin or gemfibrozil in hypertensive patients in hydrochlorothiazide monotherapy can reduce total cholesterol and LDL-cholesterol plasma levels, while significantly increasing HDL plasma levels compared to placebo. Simvastatin, however, resulted more efficient than gemfibrozil on total cholesterol or cholesterol fractions.
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PMID:[Simvastatin versus gemfibrozil in the treatment of primary hypercholesterolemia in hypertensive patients treated with hydrochlorothiazide]. 224 35

The activities of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) and 5 beta-reductase were analyzed in 39 normotensive controls and 128 patients with essential hypertension. The activity of 11 beta-HSD was obtained by dividing the 24-hour urinary tetrahydrocortisone by the sum of tetrahydrocortisol (THF) and allotetrahydrocortisol (aTHF), whereas the activity of 5 beta-reductase was obtained by dividing the 24-hour urinary THF by aTHF. The activity of 5 beta-reductase was significantly lower in essential hypertensives compared with normotensive controls (P < 0.05). However, the activity of 11 beta-HSD did not differ between normotensive controls and essential hypertensives. A positive correlation between the activities of 11 beta-HSD and 5 beta-reductase was observed in essential hypertensives (r = 0.60, P < 0.01). Neither 11 beta-HSD nor 5 beta-reductase activity correlated with indices of renal mineralocorticoid receptor activation, which were assessed by determination of plasma potassium and urinary excretion of sodium as well as potassium. Taken together, these results suggest that disturbances of one of the inactivation pathways of cortisol may contribute to the pathogenesis of hypertension.
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PMID:The activities of 5 beta-reductase and 11 beta-hydroxysteroid dehydrogenase in essential hypertension. 770 42

We compared corticosteroid metabolite excretion rates and patterns in a group of 68 subjects with untreated essential hypertension and a matched group of 48 normotensive control subjects. The ratio of tetrahydrocortisol plus allotetrahydrocortisol to tetrahydrocortisone and the ratio of allotetrahydrocortisol to tetrahydrocortisol were significantly higher in the hypertensive group. This is qualitatively similar to the situation found in patients with the syndrome of apparent mineralocorticoid excess or subjects treated with licorice or carbenoxolone where hypertension is known to arise from deficiencies of 11 beta-hydroxysteroid dehydrogenase and 5 beta-reductase activities. The equivalent ratios for corticosterone metabolites were not different between groups, but total corticosterone metabolite excretion was higher in the hypertensive group. Plasma cortisol levels were lower in hypertensive than in control subjects, but corticosterone levels were higher. This evidence supports a previous suggestion that the activities of these two enzymes may be reduced in essential hypertension, but the contribution of these changes to hypertension is not known.
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PMID:Evidence of coexisting changes in 11 beta-hydroxysteroid dehydrogenase and 5 beta-reductase activity in subjects with untreated essential hypertension. 784 56

Recently, the current authors reported the presence in normotensive male and female urines of reproducibly measurable levels of naturally occurring substances in partially purified extracts of urine with inhibitory activity like glycyrrhetic acid (GA) towards both 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) and steroid 5 beta-reductase (5 beta-SR) in vitro. Since these substances mimic two known inhibitory activities of GA, they have been named 'Glycyrrhetic Acid-Like Factors', abbreviated as 'GALFs' or, more specifically 11 beta-GALF for substance(s) active against 11 beta-OHSD, and 5 beta-GALF for those inhibitory to 5 beta-SR. Administration of glycyrrhetic acid in man leads to cortisol-dependent mineralocorticoid hypertension, owing to impaired inactivation of cortisol by 11 beta-OHSD, and may be associated with increased sensitivity to mineralocorticoids owing to impaired 5 beta-SR. In this preliminary report, the results are described of a study on the presence of GALF factors in urines collected from patients with congestive heart failure (CHF) and mild essential hypertension. The results show that in such patients there are increased amounts of both 11 beta- and 5 beta- GALFs compared to normotensive. The possible physiological significance of these results is discussed.
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PMID:Inhibitors of 11 beta-hydroxysteroid dehydrogenase and 5 beta-steroid reductase in urine from patients with congestive heart failure. 829

11 beta-hydroxysteroid dehydrogenase (11 beta HSD) has both dehydrogenase (11 beta DH) and reductase (11 beta R) activities, which catalyse the interconversion of cortisol and cortisone, and prednisolone and prednisone. This enzyme confers specificity on the mineralocorticoid receptor by local oxidation of cortisol to cortisone. Using radiolabelled cortisol 11 beta HSD activity has been shown to be lower in some cases of essential hypertension. This study investigated a novel approach to estimating 11 beta HSD activity in vivo. Plasma steroid kinetics were investigated following oral hydrocortisone (a substrate for 11 beta DH) and prednisone (a substrate for 11 beta R) in five normotensive volunteers after dexamethasone suppression of endogenous steroid production. This approach was evaluated by inducing partial deficiency of 11 beta HSD in the volunteers who took liquorice (to inhibit 11 beta DH) and then carbenoxolone (to inhibit both 11 beta DH and 11 beta R). The ratio of cortisol to prednisolone (formed from prednisone) provided a measure of the activity of both 11 beta DH and 11 beta R. At 75 min after the steroid bolus the ratio increased from 1.1 (0.6-1.3) (median, range) under control conditions to 1.2 (0.8-1.7) after liquorice (P = 0.01, n = 5), and 2.0 (1.3-5.9) after carbenoxolone (P = 0.02, n = 5). It may therefore be applied to the measurement of 11 beta HSD activity in vivo in large numbers of hypertensive patients without the use of radioisotopes.
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PMID:A non-isotopic method for estimating 11 beta hydroxysteroid dehydrogenase activity in vivo. 929 6


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