Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.23.15 (renin)
 35,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypertension and hyperpotassemia that were accompanied by normal plasma aldosterone and low renin levels and were responsive to chlorothiazide administration were found in a 29-year-old patient and two decades later in his 21-year-old son. Their renal function is normal, including response to sodium sulfate, mannitol, and aldosterone infusions. Adrenal insufficiency was excluded. The renin-aldosterone system was proved intact by physiological and pharmacologic stress and angiotensin-II infusion. Also normal were values for blood counts, blood volumes, and erythrocyte and exchangeable body potassium. The postulation of a defective cell membrane impeding potassium influx is supported by the failure of glucose and insulin infusions to substantially reduce hyperpotassemia. In the context of a hereditary disorder (the pedigree, compatible with autosomal dominant inheritance, includes five affected in two generations), hypertension is a second phenotypic character of a single defective pleiotropic gene although its pathogenesis remains unclear.
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PMID:Familial hyperpotassemia and hypertension accompanied by normal plasma aldosterone levels: possible hereditary cell membrane defect. 71 48

A 5-year-old female Siberian husky that was diagnosed as an essential hypertensive was bred several times over a 5-year period, producing a colony of 39 offspring. Thirty of the 39 animals were subjected to biweekly systemic arterial blood pressure determinations with femoral arterial puncture and were placed into two hypertensive and two normotensive groups based on mean blood pressure: Group 1 (mean blood pressure, 128 +/- 12 mm Hg), Group 2 (mean blood pressure, 121 +/- 3 mm Hg), Group 3 (mean blood pressure, 114 +/- 8 mm Hg), and Group 4 (mean blood pressure, 101 +/- 9 mm Hg). Groups 1, 2, and 3 had mean blood pressures significantly higher than that of Group 4 (p less than 0.05). Ten dogs (representatives from Groups 1, 2, and 3) were subjected to more detailed clinical testing including angiography, echocardiography, ophthalmic examination, plasma catecholamine and renin activity measurements, plasma lead and cadmium determinations, cerebrospinal fluid examination, renal profile, and serum chemistry and hematological analysis. Five unrelated normotensive Siberian huskies were compared with colony dogs by using echocardiography. Groups 1 and 2 showed a clear but statistically insignificant upward trend in left ventricular wall thickness indexed against body weights when compared with that in Group 3 and in the unrelated five normal Siberian dogs. Thus, the only specific difference from group to group in the colony at the termination of this study was the difference in mean blood pressure. Based on these data, it is possible and likely that aging will reveal changes secondary to chronic primary hypertension. The pathogenesis of this hereditary disorder remains unknown.
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PMID:Primary hypertension in a colony of dogs. 379

Bartter's syndrome is a genetic disorder which has very rarely been clinically encountered. However, it is of specific interest with respect to the hormonal layer of the kidney, including renin, angiotensin and aldosterone as well as biological alteration of the various electrolytes. The fundamental morphological manifestation of this disorder is known to be hyperplasia of juxtaglomerular cells, although, until now, no experimental studies on this condition have been reported. Demonstrated in this initial study is the remarkable hyperplasia of the juxtaglomerular cells in all terminal portions of the afferent glomerular arterioles situated near the hilum of the glomerular tuft, using a low-dose, long-term administration of calcium chelating agents. This hyperplasia reported in this paper may lead to a new procedure in the analysis of this syndrome.
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PMID:Experimental study on the hyperplasia of juxtaglomerular cells under low-dose, long-term administration of calcium chelating agents. Similar to the morphological manifestation of Bartter's syndrome. 800 Feb 45

Liddle's disease is an autosomal dominant genetic disorder characterized by severe low renin hypertension ("pseudoaldosteronism") that has been genetically linked to a locus on chromosome 16 encoding the beta-subunit of an amiloride-sensitive Na+ channel (ASSC) (15). Peripheral blood lymphocytes (PBL) express ASSC that are functionally indistinguishable from those expressed by Na(+)-reabsorbing renal epithelial cells (3, 5). The amiloride-sensitive Na+ conductance in PBL from affected and unaffected individuals from the original Liddle's pedigree was examined using whole cell patch clamp. Typically, the basal Na+ currents in cells from affected individuals were maximally activated. Basal Na+ currents in cells from unaffected individuals were minimal and could be maximally activated by superfusion with 8-(4-chlorophenylthio)adenosine 3',5'-cyclic monophosphate (CPT-cAMP). Affected cells could not be further stimulated with CPT-cAMP. Superfusion with a supermaximal concentration of amiloride (2 microM) inhibited both the cAMP-activated Na+ conductance in unaffected cells and the constitutively activated inward conductance in affected cells. Cytosolic addition of a peptide identical to the terminal 10 amino acids of the truncated beta-subunit normalized the cAMP-mediated but not the pertussis toxin-induced regulation of the mutant ASSC. The findings show that lymphocyte ASSC are constitutively activated in affected individuals, that a mutation of the beta-subunit alters ASSC responsiveness to specific regulatory effectors, and that the cellular mechanism responsible for the pathophysiology of Liddle's disease is abnormal regulation of Na+ channel activity. These findings have important diagnostic and therapeutic implications and provide a cellular phenotype for the diagnosis of pseudoaldosteronism.
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PMID:Liddle's disease: abnormal regulation of amiloride-sensitive Na+ channels by beta-subunit mutation. 877 46

Severe low-renin hypertension has few known causes. Apparent mineralocorticoid excess (AME) is a genetic disorder that results in severe juvenile low-renin hypertension, hyporeninemia, hypoaldosteronemia, hypokalemic alkalosis, low birth weight, failure to thrive, poor growth, and in many cases nephrocalcinosis. In 1995, it was shown that mutations in the gene (HSD11B2) encoding the 11beta-hydroxysteroid dehydrogenase type 2 enzyme (11beta-HSD2) cause AME. Typical patients with AME have defective 11beta-HSD2 activity, as evidenced by an abnormal ratio of cortisol to cortisone metabolites and by an exceedingly diminished ability to convert [11-3H]cortisol to cortisone. Recently, we have studied an unusual patient with mild low-renin hypertension and a homozygous mutation in the HSD11B2 gene. The patient came from an inbred Mennonite family, and though the mutation identified her as a patient with AME, she did not demonstrate the typical features of AME. Biochemical analysis in this patient revealed a moderately elevated cortisol to cortisone metabolite ratio. The conversion of cortisol to cortisone was 58% compared with 0-6% in typical patients with AME whereas the normal conversion is 90-95%. Molecular analysis of the HSD11B2 gene of this patient showed a homozygous C-->T transition in the second nucleotide of codon 227, resulting in a substitution of proline with leucine (P227L). The parents and sibs were heterozygous for this mutation. In vitro expression studies showed an increase in the Km (300 nM) over normal (54 nM). Because approximately 40% of patients with essential hypertension demonstrate low renin, we suggest that such patients should undergo genetic analysis of the HSD11B2 gene.
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PMID:A genetic defect resulting in mild low-renin hypertension. 970 24

Our research team and laboratories have concentrated on two inherited endocrine disorders, congenital adrenal hyperplasia (CAH) and apparent mineralocorticoid excess, in thier investigations of the pathophysiology of adrenal steroid hormone disorders in children. CAH refers to a family of inherited disorders in which defects occur in one of the enzymatic steps required to synthesize cortisol from cholesterol in the adrenal gland. Because of the impaired cortisol secretion, adrenocorticotropic hormone levels rise due to impairment of a negative feedback system, which results in hyperplasia of the adrenal cortex. The majority of cases is due to 21-hydroxylase deficiency (21-OHD). Owing to the blocked enzymatic step, cortisol precursors accumulate in excess and are converted to potent androgens, which are secreted and cause in utero virilization of the affected female fetus genitalia in the classical form of CAH. A mild form of the 21-OHD, termed nonclassical 21-OHD, is the most common autosomal recessive disorder in humans, and occurs in 1/27 Ashkenazic Jews. Mutations in the CYP21 gene have been identified that cause both classical and nonclassical CAH. Apparent mineralocorticoid excess is a potentially fatal genetic disorder causing severe juvenile hypertension, pre- and postnatal growth failure, and low to undetectable levels of potassium, renin, and aldosterone. It is caused by autosomal recessive mutations in the HSD11B2 gene, which result in a deficiency of 11beta-hydroxysteroid dehydrogenase type 2. In 1998, we reported a mild form of this disease, which may represent an important cause of low-renin hypertension.
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PMID:Steroid disorders in children: congenital adrenal hyperplasia and apparent mineralocorticoid excess. 1053 1

Blood pressure is determined by the product of cardiac output, intravascular volume, and peripheral resistance. Because hormones are involved in blood pressure regulation and affect these parameters, hypertension is a prominent feature of certain adrenal enzymatic abnormalities. In this report, two steroid-dependent forms of genetic low-renin hypertension are examined: 11beta-hydroxylase deficiency and apparent mineralocorticoid excess. 11beta-Hydroxylation is an enzymatic function necessary for the biosynthesis of cortisol by the zona fasciculata (ZF) of the adrenal cortex. Defects in this step lead to the abnormally increased production by the ZF of the steroid 11-deoxycorticosterone (DOC), a moderately potent mineralocorticoid, which causes sodium retention and volume expansion that result in hypertension. Further, the excess production of adrenal androgens leads to virilization, prenatally in the genetic female, and postnatally in both sexes. The disorder of 11beta-hydroxylase deficiency is due to an autosomal recessive defect of the enzyme protein-encoding gene CYP11B1. Numerous mutations in CYP11B1 causing 11beta-hydroxylase deficiency have been characterized. Apparent mineralocorticoid excess is a potentially fatal genetic disorder causing severe juvenile hypertension, pre- and postnatal growth failure, and low to undetectable levels of potassium, renin, and aldosterone. It is caused by autosomal recessive mutations in the HSD11B2 gene, which result in a deficiency of 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2).
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PMID:Hormonal hypertension in children: 11beta-hydroxylase deficiency and apparent mineralocorticoid excess. 1115 48

Apparent mineralocorticoid excess (AME) is a potentially fatal genetic disorder causing severe juvenile hypertension, pre- and postnatal growth failure, hypokalemia and low to undetectable levels of renin and aldosterone. It is caused by autosomal recessive mutations in the HSD11B2 gene, which result in a deficiency of 11 beta-hydroxysteroid dehydrogenase type 2 (11 beta-HSD2). The 11 beta-HSD2 enzyme is responsible for the conversion of cortisol to the inactive metabolite cortisone and, therefore, protects the mineralocorticoid receptors from cortisol intoxication. In 1998, a mild form of this disease was reported, which might represent an important cause of low-renin hypertension. Early and vigilant treatment might prevent or improve the morbidity and mortality of end-organ damage.
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PMID:Apparent mineralocorticoid excess. 1130 34

Remarkable regional differences in the annual incidence of endstage renal disease (ESRD) was found within Japan, which has a relatively homogeneous ethnic composition. In addition, there existed no regional difference in the incidence of ESRD due to polycystic kidney disease, the major genetic disorder of the kidneys. These findings suggest that the presence of factors other than genetic disposition contribute to the differences. On the other hand, there were similar regional variations in the incidences of ESRD between two causes of ESRD: chronic glomerulonephritis and diabetic nephropathy. Because it is unlikely that the regional distribution of underlying disease incidence and the disease-specific progression rate would be similar for two different causes, this observation suggests that factors governing the progression rate, which operate commonly for all causes of ESRD but differ among regions, may play an important role in generating the regional differences. Finally, we examined regional differences in the amounts of inhibitors of the renin-angiotensin system used, especially angiotensin-converting enzyme (ACE) inhibitors, in our search for an explanation of the regional differences in ESRD dynamics. Among antihypertensive agents examined, only ACE inhibitors were negatively correlated with the annual incidence of ESRD. The renal protective effects of ACE inhibitors have been established by results with animal models of progressive nephropathy and by large-scale clinical trials. Our epidemiological results for Japan as a whole show the same protective effects still more convincingly from a different approach. It is not completely clear yet at present, however, how regional variations in the incidence of ESRD are generated. If we could identify in future the factors that contribute to the regional differences, strategies for the treatment of renal disease will become available from different angles. Thus, much effort will be encouraged for the further analysis of regional differences in ESRD dynamics.
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PMID:Proposal for mapping renal failure in Japan and its application for strategy to arrest endstage renal disease. 1654 72

Congenital adrenal hyperplasia due to steroid 11beta-hydroxylase deficiency is a genetic disorder of steroidogenesis, transmitted as an autosomal recessive trait. It is associated with low renin hypertension, hypokalemia, hyperandrogenemia and genital ambiguity in affected females. Mutations in the CYP11B1 gene, causing 11beta-hydroxylase deficiency in the zona fasciculata in the adrenal cortex, have been identified. The indicators of congenital adrenal hyperplasia caused by 11beta-hydroxylase deficiency, include increased serum concentrations of desoxycorticosterone, 11 deoxycortisol and delta4-androstenedione, and suppressed plasma renin concentrations. The disorder is treated by administration of glucocorticoids.
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PMID:Steroid 11beta- hydroxylase deficiency congenital adrenal hyperplasia. 1829 61


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