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

In vitro metabolism of progesterone and cholesterol by the adrenal glands and hepatic delta 4-reductase activity of SHR and ARH were investigated to clarify the possible hyperactivity of the pituitary-adrenal axis and abnormal steroid metabolism in SHR. The increased conversion rate of progesterone to 11 beta-hydroxyprogesterone, corticosterone and 18-hydroxy-deoxycorticosterone and the increased biosynthesis of pregnenolone from cholesterol were noted in ARH, which were similar to those seen with chronic ACTH administration. On the other hand, adrenal steroidogenesis in SHR showed no difference from that of control. Therefore the apparently normal adrenal steroidogenesis in SHR may suggest that the adrenal gland is not involved in the spontaneous hypertension of rats. The markedly decreased hepatic delta 4-reductase activity in ARH and SHR was observed in this investigation.
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PMID:Adrenal steroidogenesis and hepatic corticosteroid metabolism in hypertensive rats. 66 27

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

Patients with the syndrome of apparent mineralocorticoid excess and those who ingest licorice show markedly decreased 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) and 5 beta-reductase activity; both are important for the deactivation of glucocorticoids and other steroid hormones. Glycyrrhetinic acid (GA), present as its glycoside in licorice, is a potent inhibitor of both 11 beta-OHSD and 5 beta-reductase and, as we have also shown, confers Na(+)-retaining properties on glucocorticoids and amplifies those of aldosterone and deoxycorticosterone. We report the results of our initial studies demonstrating the presence of naturally occurring substances, which inhibit both 5 beta-reductase and 11 beta-OHSD as does GA, in partially purified extracts of urine from normotensive men and nonpregnant and pregnant women. Since these substances exhibit GA-like activity, we have termed them GA-like factors (GALFs). This "inhibitory" material is heat stable and does not react with ninhydrin; the majority is not extractable with ethyl acetate and thus is not a "free" steroid. When further purified by high-performance liquid chromatography with a methanol/water gradient, the majority of these GALFs appeared in two regions of inhibitory activity. The chemical nature of this material is currently being investigated. These experiments indicate that normal human urine contains GALFs that may play a role in Na+ homeostasis and regulation of blood pressure.
Hypertension 1992 Sep
PMID:Detection of glycyrrhetinic acid-like factors (GALFs) in human urine. 151 55

Cases of sexual immaturity and male pseudohermaphroditism due to disorders such as androgen resistance, 5 alpha-reductase deficiency, cholesterol desmolase deficiency, 3 beta-hydroxysteroid dehydrogenase deficiency, and testicular and ovary dysgenesis can easily be distinguished from 17 alpha-OHD. None of these disturbances result in hypertension. In the only other form of juvenile hypertension due to congenital adrenal hyperplasia, 11 beta-OHD, androgen excess leads to female pseudohermaphroditism and precocious puberty in the male patient. Patients with dexamethasone-suppressible hyperaldosteronism present with no sexual abnormalities. A diagnosis of 17 alpha-OHD can be readily assumed in the female patient with primary amenorrhea, hypertension, and hypokalemia. The absence of aldosterone, a measurement that is readily available, establishes this diagnosis even without the measurement of DOC.
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PMID:17 alpha-hydroxylation deficiency. 187 98

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

For the past 40 years, adrenoreceptors have been studied as the biomolecular mediators of tissue response to catecholamines. An expanded role of alpha-adrenoreceptors in the regulation of risk factors for coronary heart disease (CHD) has recently emerged. Hypercholesterolaemia, hypertension, and cigarette smoking are the major risk factors and their interactions are associated with increased mortality. Control of hypertension alone has failed to reduce the risk of CHD. Conversely, reduction of elevated total cholesterol and low density lipoprotein (LDL)-cholesterol has been shown to lower the risk of CHD. As a result, multiple risk factor approaches to the management of patients have evolved in attempts to reduce deaths from CHD. Selective alpha 1-adrenoreceptor antagonists appear to have a dual function in CHD risk management since they control elevated blood pressure by peripheral vasodilatation and reduce atherogenic lipids by several mechanisms. With selective alpha 1-blockade, the number of LDL-cholesterol receptors is up-regulated and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG Co-A reductase) activity is suppressed causing reductions in total cholesterol, LDL-cholesterol, and apoprotein B levels. Effects on intermediary metabolism reduce synthesis of very low density lipoprotein (VLDL) which contributes to a reduction of total triglyceride levels and, to a lesser extent, to a reduction of total cholesterol levels. Increased lipoprotein lipase activity leads to reduced total triglyceride and VLDL levels and to increased high density lipoprotein (HDL)-cholesterol levels. As demonstrated by the initial prospective data from Phase I of the Treatment of Mild Hypertension Study (TOMHS), both reduction of raised blood pressure and beneficial lipid modifications are sustained (1 year) with selective alpha 1-blockade. The prospective benefits on morbidity and mortality from CHD of such favourable changes in these two major risk factors remain to be quantified.
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PMID:Alpha 1-adrenoreceptor blockade and the molecular basis of lipid metabolism alterations. 197 19

1. From an earlier cross-sectional survey of 343 public servants, 15 pairs of non-smoking teetotallers and heavy drinkers (alcohol intake more than 350 mL/week) were matched for age and adiposity and utilized for a case-control study of the effects of alcohol on 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) activity and blood pressure. 2. Two successive 24 h urine collections were analysed by radio-immunoassay (RIA) for cortisol excretion, and for the cortisol and cortisone metabolites, tetrahydrocortisol (THC), allo-tetrahydrocortisol (allo-THC) and tetrahydrocortisone (THE), by capillary column gas chromatography. 3. Heavy drinkers had higher systolic and diastolic blood pressure (BP) than teetotallers (132.6 +/- 2.5 vs 123.2 +/- 1.3 and 78.7 +/- 1.6 vs 71.7 +/- 1.4, respectively; unpaired t-test, P less than 0.01). Twenty-four-hour urinary sodium and cortisol excretion were similar in the two groups. 4. The THC plus allo-THC:THE ratio was similar in drinkers and teetotallers (1.81 +/- 0.20 vs 2.03 +/- 0.20), consistent with no effect of alcohol on 11 beta-OHSD activity. The ratio of THC to allo-THC was increased in drinkers compared with teetotallers (1.49 +/- 0.18 vs 1.05 +/- 0.13; unpaired t-test, P less than 0.05), consistent with either a decrease in 5 alpha-reductase activity or an increase in 5 beta-reductase activity. 5. This study provides no evidence for alcohol-related inhibition of 11 beta-OHSD, despite substantially higher blood pressures in heavy drinkers compared to teetotallers. Such an effect is, therefore, unlikely to contribute significantly to the mechanism of alcohol-related hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Urinary steroid profiles and alcohol-related blood pressure elevation. 206 72

Coronary heart disease is the leading cause of death among patients with non-insulin-dependent diabetes mellitus (NIDDM). NIDDM patients have a high frequency of dyslipidemia, which along with obesity, hypertension, and hyperglycemia may contribute significantly to accelerated coronary atherosclerosis. Because risk factors for coronary heart disease are additive and perhaps multiplicative, even mild degrees of dyslipidemia may enhance coronary heart disease risk. Therefore, therapeutic strategies for management of NIDDM should give equal emphasis to controlling hyperglycemia and dyslipidemia. The National Cholesterol Education Program recently issued guidelines for treatment of hyperlipidemia in adults including diabetic patients. Because of the unique features of diabetic dyslipidemia, however, we suggest that certain modifications in these guidelines be made to meet specific needs of diabetic patients. For example, therapeutic goals for serum cholesterol reduction should be lower in diabetic patients than in nondiabetic subjects. Particular emphasis should be given to weight reduction in NIDDM patients. In some diabetic patients, monounsaturated fatty acids may be a better replacement for saturated fatty acids than carbohydrates. The target for cholesterol lowering should include both very-low-density lipoprotein and low-density lipoprotein (LDL) (non-high-density lipoprotein) rather than LDL alone. To obtain a substantial reduction of cholesterol levels, drug therapy may be required in many patients. However, first-line drugs for nondiabetic patients (nicotinic acid and bile acid sequestrants) may be less desirable in NIDDM patients than hydroxymethylglutaryl coenzyme A (HMG CoA) reductase inhibitors and even fibric acids. In fact, HMG CoA reductase inhibitors may be the drugs of choice for NIDDM patients with elevated LDL cholesterol and borderline hypertriglyceridemia, whereas gemfibrozil appears preferable for NIDDM patients with severe hypertriglyceridemia.
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PMID:Management of dyslipidemia in NIDDM. 219 Jul 70

This study reports the results of a 6-month, open-label multicenter study of the efficacy and tolerability of lovastatin, a 3-hydroxy-3-methylglutaryl co-enzyme A (HMG CoA) reductase inhibitor, in the management of nonfamilial primary hypercholesterolemia. The study enrolled 489 patients with elevated total serum cholesterol levels, whose lipids were not controlled sufficiently by diet. There was good representation of gender (48.3% women and 51.7% men), age (mean 57, range 25 to 83) and hypertension status (55.4% normotensive and 43.6% hypertensive) in the sample. Within 1 month of lovastatin therapy, total cholesterol was reduced 19% (from a mean of 269 to 217 mg/dl, low-density lipoprotein (LDL) cholesterol was reduced 27% (191 to 140 mg/dl), high-density lipoprotein (HDL) cholesterol increased 6% (42.6 to 45.1 mg/dl), the ratio of total cholesterol to HDL was reduced 24% (6.7 to 5.1) and the ratio of LDL to HDL was reduced 30% (4.7 to 3.3). These results were consistent across age group, gender and hypertension status, and were maintained for a period of 6 months of therapy. Lovastatin was generally well tolerated. Of the 489 patients enrolled, 449 (92%) completed 6 months of therapy. Only 21 (4%) withdrew because of adverse experience regardless of cause. None of the few serious adverse experiences (e.g., myocardial infarction) could be attributed to the drug. Abnormal laboratory values during the 6 months of therapy were within expectations. Seventy-four patients had at least 1 abnormal value during 6 months of treatment. Of these, 42 had at least 1 mild to moderate creatine phosphokinase elevation during this period. Only 1 patient had an adverse change on ophthalmologic examination: a posterior subcapsular opacity in both eyes just visible on 6-month examination.
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PMID:Efficacy and tolerability of lovastatin in a six-month study: analysis by gender, age and hypertensive status. 220 30


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