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

Increased mineralocorticoid activity has been associated with elevated urinary levels of 19-nordeoxycorticosterone in several forms of experimental and human hypertension. Biosynthesis of 19-norsteroids involves hydroxylation of the C-19 methyl group. We synthesized the 4-hydroxy analogs of deoxycorticosterone, deoxycorticosterone acetate, progesterone, and androstenedione and evaluated them as inhibitors of deoxycorticosterone 11 beta/19-hydroxylase using hamster adrenal mitochondrial preparations. These 4-hydroxy analogs were inhibitors of this P 450 hydroxylase, with approximately 10 times weaker affinity than their respective natural substrates. 4-Hydroxydeoxycorticosterone was the most potent inhibitor evaluated in this study. The half-maximal inhibitory concentration of deoxycorticosterone hydroxylation was 5 microM, 15 microM, more than 50 microM, and 14 microM, respectively, for the above compounds.
Steroids 1990 Sep
PMID:Inhibition of hamster adrenal 11 beta/19-hydroxylase activity. 228 13

Ingestion of licorice or treatment with chemical derivatives of glycyrrhetinic acid (GA), an active principle of licorice, can cause hypertension, sodium retention, and hypokalemia. Although GA has been shown to inhibit 11 beta-hydroxysteroid dehydrogenase, it may not be the only hepatic enzyme affected by this licorice derivative. Therefore, we studied the effects of GA on other major hepatic steroid-metabolizing enzymes from adrenalectomized male rats using aldosterone as the substrate; namely, delta 4-5 alpha- and delta 4-5 beta-reductases and 3 alpha- and 3 beta-hydroxysteroid dehydrogenases (3 alpha- and 3 beta-HSD). From these in vitro studies, we demonstrated that GA does not affect either microsomal 5 alpha-reductase or cytosolic 3 alpha-HSD activity. However, GA is a potent inhibitor of cytosolic 5 beta-reductase; the K(is) and K(ii) were calculated from enzyme kinetic analysis to be 6.79 and 5.41 microM, respectively, using the Cleland equation, indicating that GA is a noncompetitive inhibitor of aldosterone. In addition, GA specifically inhibited microsomal 3 beta-HSD enzyme activity by what appears to be a competitive inhibition mechanism, causing a build-up of the intermediate, 5 alpha-dihydroaldosterone (DHAldo). Thus, this study has indicated that GA has a profound effect on hepatic ring A-reduction of aldosterone. Inhibition of 5 beta-reductase and 3 beta-HSD results in decreased synthesis of both 3 alpha, 5 beta-tetrahydroaldosterone (THAldo) and 3 beta, 5 alpha-THAldo and, hence, accumulation of aldosterone and 5 alpha-DHAldo, both potent mineralocorticoids.(ABSTRACT TRUNCATED AT 250 WORDS)
Steroids 1990 Feb
PMID:The effects of the licorice derivative, glycyrrhetinic acid, on hepatic 3 alpha- and 3 beta-hydroxysteroid dehydrogenases and 5 alpha- and 5 beta-reductase pathways of metabolism of aldosterone in male rats. 232 27

19-Hydroxyandrostenedione (19-OHA) is secreted from the adrenal glands in men and women and also from the placenta during pregnancy. It has been found to cause hypertension in animal models. We have synthesized [7,7-2H2]-19-OHA with high deuterium content and, together with [7,7-2H2]A and [9,11-2H2]estrone (E1), have developed a quantitative assay of serum level 19-OHA, A, and E1 using the gas chromatography/mass spectrometry-mass fragmentography method to monitor individual subjects throughout pregnancy. The labeled 19-OHA, used as internal standard, showed only 6.73% of unlabeled compound. Recovery of standard 19-OHA, A, and E1 (5,000 pg each) added to male plasma was 97.4 +/- 2.3%, 96.3 +/- 2.1%, and 100.1 +/- 4.1% (mean +/- SD), respectively; the intraassay coefficient of variation was 2.1%, 3.5%, and 3.8%, respectively. Ten pregnant subjects without complications and 10 pregnant subjects near term with hypertension were selected (with informed consent). The 19-OHA and E1 serum concentrations of maternal venous blood from uncomplicated pregnancies increased significantly as gestation progressed (19-OHA: first trimester, 225 +/- 72; second trimester, 656 +/- 325; third trimester, 1,518 +/- 544 pg/ml), reaching the highest level at delivery (19-OHA: 1,735 +/- 684 pg/ml). Whereas a positive correlation was found between the level of 19-OHA and E1, no apparent change of the A level was observed during pregnancy. Levels of the three steroid hormones in pregnancy complicated by hypertension in the second and third trimester were not found to be significantly different from those of normal pregnancy (19-OHA of hypertensive subjects: second trimester, 762 +/- 349; third trimester, 1,473 +/- 491 pg/ml).(ABSTRACT TRUNCATED AT 250 WORDS)
Steroids 1990 Apr
PMID:Serum level of 19-hydroxyandrostenedione during pregnancy and at delivery determined by gas chromatography/mass spectrometry. 233 47

Eight hundred and seventy-nine patients with Bell's Palsy were seen over a 10-year period. There was a distinct female preponderance and the peak incidence occurred in the second to fourth decades. There did not appear to be an increased incidence of either hypertension or diabetes but there was a definite increased risk during pregnancy. Half of the patients had an incomplete palsy and they all recovered within a few weeks of onset. Those patients with complete palsy but without evidence of degeneration also all recovered but took longer to do so. If degeneration was evident the chance of recovery was only 50 per cent. Steroids did not appear to influence the outcome of Bell's Palsy.
 ...
PMID:Idiopathic facial nerve palsy (the effect of treatment with steroids). 339 32

The average plasma concentration of androstenedione (A) in 67 hypertensive pregnant women (mean 25.7 nmol/L, SD 10.0) was significantly higher (p less than 0.001) than that in 71 normotensive pregnant women (mean 14.2 nmol/L, SD 5.6). Androstenedione concentration decreased significantly (p less than 0.01) from this higher level with increasing gestation in pregnancies complicated by hypertension. In the normotensive group there was no significant correlation between androstenedione concentration and gestation, but a sharp increase in androstenedione concentration occurred prior to delivery. The androstenedione concentration in 18 hypertensive patients with fulminating disease (mean 30.7 nmol/L, SD 11.9) was significantly higher (p less than 0.02) than that in 49 hypertensive patients (mean 23.9 nmol/L, SD 8.7). The correlation between androstenedione and 19-hydroxyandrostenedione (19-OH-A) concentrations in plasma was highly significant; for 98 pairs, r = 0.43, p less than 0.001.
Steroids
PMID:Plasma androstenedione in normotensive and hypertensive pregnancy. 344 84

The presence of angiotensinogen messenger RNA (mRNA) was assessed in total RNA extracted from hepatoma, glioma, neuroblastoma, and glioma-neuroblastoma hybrid cell lines. Total RNA from 1 X 10(7) cells was extracted, transferred to a membrane, and hybridized with a 32P-labeled, full-length (1650-base pair) rat angiotensinogen complementary DNA (cDNA). Angiotensinogen RNA sequences could be definitively detected only in hepatoma cells. Steroids were used in an attempt to increase the angiotensinogen mRNA level. Dexamethasone (2 X 10(-6) M) or 17 beta-estradiol (1 X 10(-7) M) was added to the cultures 18 to 24 hours prior to harvest. Dexamethasone treatment of the hepatoma cells resulted in a large increase in angiotensinogen mRNA, whereas estradiol had no effect. Steroids failed to induce detectable levels of angiotensinogen mRNA in total RNA from the other cell lines. That the RNA was intact was ensured by hybridizing duplicate Northern blots to a 32P-labeled actin cDNA. Actin mRNA sequences were detected in all cell lines. Blot hybridization of poly(A)+RNA resulted in the visualization of a weak angiotensinogen mRNA signal for a glioma cell line and a glioma-neuroblastoma hybrid line. However, the ability to detect angiotensinogen mRNA in a cell may depend on the phenotype expressed, which can be governed by culture conditions.
Hypertension 1987 Jun
PMID:Presence of angiotensinogen messenger RNA in various cultured cell lines. 359 87

Since catechol estrogens are potent competitive inhibitors of catechol-O-methyl transferase (COMT), it has been suggested that they may prolong the half-life of catecholamines which in turn can cause hypertension. Thus, experiments were carried out to study the effect of catechol estrogens on blood pressure in the male rat following chronic administration. Results demonstrate that 2-hydroxyesterone (2,3-dihydroxyestra-1,3,5(10)-trien-17-one) and 2-hydroxy-estradiol (estra-1,3,5(10)-triene-2,3,17 beta-triol) even when administered in high doses do not alter blood pressure.
Steroids 1983 Dec
PMID:The absence of a catechol estrogen effect on blood pressure in the male rat. 609 75

The clinical, biological, and immunological alterations of 20 patients with histologically confirmed classical panarteritis nodosa have been studied. Characteristic angiographic changes were present in 14 cases. There were 14 males and six females, with a mean age of 50 years. The main clinical manifestations were: fever (90%), peripheral nervous system involvement (80%), renal involvement (65%), arterial hypertension (60%), arthropathy (80%), and cutaneous lesions (45%). In most cases there was elevated VSG and alpha 2-globulin, anemia and leukocytosis. HBsAg positivity was found in five patients. The immunological study revealed a polyclonal immunoglobulin increase, changes in the complement components, and a quantitative and qualitative decrease of T lymphocytes. Steroids and immunosuppressive treatment were given to eight patients, and steroids along to 11 patients. The clinical evolution of 17 patients was followed; four patients died, all of them belonging to the group treated with steroid alone.
 ...
PMID:[Classical panarteritis nodosa: a clearly defined entity. Analysis of 20 cases (author's transl)]. 611 4

Membranous nephropathy is the most frequent histological category among black children with nephrotic syndrome. In this study 31 African children with this condition are described. There were more boys than girls and the peak age was four to 11 years. The incidence of this histological category and clinical outcome in the African children were similar to these features in adults with membranous nephropathy. During a follow-up period of up to six years there was spontaneous remission in a third of patients, persistent proteinuria in just over a third (37.5%) and persistent relapse in under a third (29.2%). Hypertension occurred more frequently (19.3%) and spontaneous remission less often (33.3%) than in children with membranous nephropathy elsewhere. Hypertension, the lower remission rate and persistence of proteinuria during the course of the disease were similar to the disease seen in adults. Renal failure was not encountered in any patients. Steroids were of little value in the treatment of these children. Five children (16.2%) had associated infections. HBsAg was present in three of six children tested.
 ...
PMID:Extramembranous nephropathy in black South African children. 619 44

Eight patients with acute exacerbations of lupus nephritis were treated with nine courses of alternate day intravenous methylprednisolone pulse therapy, for three doses of 30 mg/kg/day. They were followed for 24 to 68 months (mean 35.6) post pulse. Stabilization of renal function was observed. Proteinuria declined, antinuclear antibody titers fell and low serum complement levels improved. Steroids were discontinued by 24 months in four patients, and switched to alternate day therapy in the remaining five patients. No patient required the addition of cytotoxic therapy. Transient post pulse elevation of serum creatine was observed with return to pre pulse renal function by 1 month. Exacerbation of hypertension in two of the four known hypertensive patients occurred during pulse therapy; in one patient, this was associated with angina. No other untoward side effects were observed. In our experience, pulse therapy is an effective form of treatment in a subset of patients with lupus nephritis who have had recent worsening renal function. Pulse therapy may allow such patients to avoid the hazards associated with conventional long-term high dose oral corticosteroids as well as those of cytotoxic agents.
 ...
PMID:Methylprednisolone pulse therapy for lupus nephritis: a followup study. 633 63


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>