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)

To evaluate the response of circulating intact parathyroid hormone (iPTH) on myocardial hypertrophy in hemodialysis (HD) patients with secondary hyperparathyroidism (SHPT), echocardiographic and neurohormonal assessments were performed over a 15-week period in 15 HD patients with SHPT before and after calcitriol treatment and 10 HD control patients with SHPT not receiving calcitriol therapy. We prospectively studied a group of 15 patients with significantly elevated iPTH levels (iPTH >450 pg/mL) receiving calcitriol (2 microg after dialysis twice weekly). Clinical assessment, medication status, and biochemical and hematological measurements were performed once a month. Throughout the study, calcium carbonate levels were modified to maintain serum phosphate levels at less than 6 mg/dL, but body weight, antihypertensive medication, and ultrafiltration dose remained constant. In patients treated with calcitriol, an adequate reduction of iPTH levels was found (1,112 +/- 694 v 741 +/- 644 pg/mL; P < 0.05) without changes in values of serum ionized calcium (iCa++), phosphate, or hematocrit. Blood pressure (BP), cardiac output (CO), and total peripheral resistance (TPR) did not significantly change. After 15 weeks of treatment with calcitriol, M-mode echocardiograms showed pronounced reductions in interventricular wall thickness (13.9 +/- 3.6 v 12.8 +/- 3.10 mm; P = 0.01), left ventricular posterior wall thickness (12.5 +/- 2.4 v 11.3 +/- 1.8 mm; P < 0.05), and left ventricle mass index (LVMi; 178 +/- 73 v 155 +/- 61 g/m2; P < 0.01). However, in control patients, these changes were not found after the treatment period. In addition, sequential measurements of neurohormonal mediator levels in patients receiving calcitriol showed that plasma renin (18.5 +/- 12.7 v 12.3 +/- 11.0 pg/mL; P = 0.007), angiotensin II (AT II; 79.7 +/- 48.6 v 47.2 +/- 45.7 pg/mL; P = 0.001), and atrial natriuretic peptide (ANP; 16.6 +/- 9.7 v 12.2 +/- 4.4 pg/mL; P = 0.03) levels significantly decreased, whereas antidiuretic hormone (ADH), epinephrine, and norepinephrine levels did not change significantly. The percent change in LVMi associated with calcitriol therapy had a strong correlation with the percent change in iPTH (r = 0.52; P < 0.05) and AT II (r = 0.47; P < 0.05) levels. We conclude that the partial correction of SHPT with intravenous calcitriol causes a regression in myocardial hypertrophy without biochemical or hemodynamic changes, such as heart rate, BP, and TPR. The changes in plasma levels of iPTH and, secondarily, plasma levels of neurohormones (especially AT II) after calcitriol therapy may have a key role in attenuating ventricular hypertrophy in SHPT.
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PMID:Intravenous calcitriol regresses myocardial hypertrophy in hemodialysis patients with secondary hyperparathyroidism. 991 70

Pseudo-hypoaldosteronism (PHA) is due to mineralocorticoid resistance and manifests as hyponatremia and hyperkalemia with increased plasma aldosterone levels. It may be familial or secondary to abnormal renal sodium handling. We report the case of a 54-year-old woman with multifocal cancer of the colon, who developed PHA after subtotal colectomy, ileal resection and jejunostomy. She was treated with 6 g of salt daily to prevent dehydration, which she stopped herself because of reduced fecal losses. One month later she was admitted with signs of acute adrenal failure, i.e. fatigue, severe nausea, blood pressure of 80/60 mmHg, extracellular dehydration, hyponatremia (118 mmol/l); hyperkalemia (7.6 mmol/l), increased blood urea nitrogen (BUN) (200 mg/dl) and creatininemia (2.5 mg/dl), and decreased plasma bicarbonates level (HCO3-: 16 mmol/l; N: 27-30). However, the plasma cortisol was high (66 microg/100 ml at 10:00 h; N: 8-15) and the ACTH was normal (13 pg/ml, N: 10-60); there was a marked increase in plasma renin activity (>37 ng/ml/h; N supine <3), active renin (869 pg/ml; N supine: 1.120), aldosterone (>2000 pg/ml; N supine <150) and plasma AVP (20 pmol/l; N: 0.5-2.5). The plasma ANH level was 38 pmol/l (N supine: 5-25). A urinary steroidogram resulted in highly elevated tetrahydrocortisol (THF: 13.3 mg/24h; N: 1.4+/-0.8) with no increase in tetrahydrocortisone (THE: 3.16 mg/24h; N: 2.7+/-2.0) excretion, and with low THE/THF (0.24; N: 1.87+/-0.36) and alpha THF/THF (0.35; N: 0.92+/-0.42) ratios. The number of mineralocorticoid receptors in mononuclear leukocytes was in the lower normal range for age, while the number of glucocorticoid receptors was reduced. Small-bowel resection in ileostomized patients causes excessive fecal sodium losses and results in chronic sodium depletion with contraction of the plasma volume and severe secondary hyperaldosteronism. Nevertheless, this hyperaldosteronism may be associated with hyponatremia and hyperkalemia suggesting PHA related to the major importance of the colon for the absorption of sodium. In conclusion, this case report emphasizes 1) the possibility of a syndrome of acquired PHA with severe hyperkalemia after resection of the ileum and colon responding to oral salt supplementation; 2) the major increase in AVP and the small increase in ANH; 3) the strong increase in urinary THF with low THE/THF and alpha THF/THF ratios; 4) the normal number of lymphocytic mineralocorticoid receptors outside the acute episode.
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PMID:Transient pseudo-hypoaldosteronism following resection of the ileum: normal level of lymphocytic aldosterone receptors outside the acute phase. 1019 79

Chronic metabolic acidosis (CMA) in human beings is characterized by increased renin-angiotensin-aldosterone (RAA) activity and cortisol secretion as well as nitrogen wasting. The purpose of this study was to examine whether and to what extent increased RAA activity (i.e., angiotensin II or aldosterone) regulates acid-base equilibrium in CMA and thus might co-determine the severity of acidosis. CMA was induced in 8 normal subjects by oral NH4Cl administration (2.1 mmol/kg body weight per day) for 7 days, followed by a 7-day period of spironolactone (100 mg, 4 times a day by mouth), followed by a 4-day period of spironolactone and losartan (100 mg, every day by mouth). NH4Cl feeding was continued during all study periods. Spironolactone resulted in exacerbation of acidosis ((HCO3)p decreased from 19.8+/-0.4 mmol/L to 17.7+/-0.6 mmol/L, P<.005) because of a large increase in endogenous acid production, as evidenced by significant increases in net acid excretion (116 to 185 mmol/day, P<.005), urinary anion gap (+31 mEq/day, P<.05), and sulfate excretion (+32 mEq/day, P<.05). Plasma potassium increased from 4.2 to 4.6 mmol/L (P<.05) because of decreased urinary potassium excretion (from 108 to 92 mmol/day, P<.05). Plasma angiotensin II, cortisol, aldosterone, urinary aldosterone, urinary tetrahydrocortisol, free cortisol, and nitrogen excretion increased significantly. The subsequent addition of losartan to spironolactone administration resulted in further exacerbation of acidosis ((HCO3)p decreased to 15.7+/-0.4 mmol/L, P<.05) and hyperkalemia (5.0 mmol/L, P<.05) with no change in plasma anion gap. Renal potassium excretion decreased from 92 to 73 mmol/day (P<.05) on day 1. Exacerbation of acidosis was accounted for by a renal mechanism, as evidenced by the significant decrease in net acid excretion and unchanged urinary unmeasured anion and nitrogen excretion. We conclude the following: (1) AT-1 blockade by losartan exacerbates acidosis by inducing a distal-tubular acidification defect. Angiotensin II is an important modulator of the renal acid excretory response to CMA in human beings. (2) Inhibition of aldosterone action by spironolactone in CMA results in an increase in endogenous acid production and exacerbates acidosis by a non-renal mechanism that is mediated, at least in part, by exacerbated hyperglucocorticoidism.
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PMID:Acid-base and endocrine effects of aldosterone and angiotensin II inhibition in metabolic acidosis in human patients. 1107 65

Insulin-mineral corticoids effects on extrarenal K+ metabolism in dialysis patients. During the inter-dialytic interval in dialyzed patients, hydrogen and potassium ions are regulated by extrarenal mechanisms. We studied the hormonal and acidotic effects on the extrarenal potassium metabolism, in selected, anuric and stable, hemodialysis patients. Fifteen patients, were grouped according to the mean mid-week pre-dialysis K+ over the past 12 months: > 6.0 mEq/L (G1, n=5), = 5.1-6.0 mEq/L (G2, n=5), < or = 5.0 mEq/L (G3, n=5). After a mid-week hemodialysis session and 12 h fasting, they received 1 g/Kg glucose p.os (A). Insulin, aldosterone, renin, pH, HCO3-, glucose, body weight, blood pressure and heart rate were measured before and 60' after the meal. We recorded the same parameters, except insulin, in 15 patients, similarly grouped, before hemodialysis (T0) and on 3 consecutive off dialysis days (T1-T3); G1 received fluorohydrocortisone (FHC) 0.1 mg-0.3 mg/day, according to body weight and G3 spironolactone (SLT) 200 mg per day. G2 were controls (B). (A) A significant rise in glycemia (81 +/- 23 to 157 +/- 52 mg/dL, P<0.001) and insulin (11.8 +/- 6.2 to 46.8 +/- 19.5 microU/mL, P<0.001), with a drop in K+ (5.1 +/- 0.6 to 4.8 +/- 0.7 mEq/L, P=0.001) and aldosterone (453 +/- 373 to 383 +/- 364 pg/mL, P<0.01), were noted at T60 vs. T0, in all groups. Insulin levels correlated negatively (r=-0.54, P<0.04) to serum K+ at T60, in all patients. (B) No major pH, HCO3 and aldosterone changes were observed in the 3 groups. Despite that, K+ dropped in G1 by FHC (6.7 +/- 0.9 to 5.9 +/- 0.6 mEq/L, P<0.05), rose in G3 by SLT (4.4 +/- 0.4 to 5.4 +/- 0.3 mEq/L, P<0.05) and remained unchanged in controls (5.8 +/- 0.2 to 5.8 +/- 0.6 mEq/L), (T0 vs T3 pre-dialysis values). Glucose significantly lowered K+ by promoting adequate insulin secretion. Drugs affecting aldosterone action significantly influenced potassium metabolism. Acid-base balance was not important in K+ handling in steady state anuric dialysis patients.
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PMID:Insulin and mineralocorticoids influence on extrarenal potassium metabolism in chronic hemodialysis patients. 1177 23

Hypokalemic paralysis is a medical emergency due to the risks of cardiac arrhythmia, respiratory failure, and rhabdomyolysis. Besides supplementing patients with KCl to hasten recovery, the astute physician must search for the underlying cause to avoid missing a treatable and curable disorder. We report on an elderly Korean man who presented with marked limb paralysis, myalgias, and mild hypertension. He had prostate cancer treated with orchiectomy and hormone therapy 2 years previously. The major biochemical abnormalities were hypokalemia (K+: 1.7 mmol/l) associated with high renal K+ wasting and metabolic alkalosis (HCO3-: 42.6 mmol/l). Low plasma renin activity, low aldosterone concentration, and normal cortisol concentration pointed to a state of pseudohyperaldosteronism. While reviewing his drug history, the patient revealed he had been consuming eight packs (100 ml/pack) of a Korean herbal tonic daily to treat his prostate cancer for the past 2 months. A significant amount of glycyrrhizic acid (0.23 mg/ml), an active ingredient of licorice, was detected in the tonic. Discontinuation of the herbal tonic along with KCl supplementation achieved recovery in 2 weeks. As many complementary/alternative medicines for cancer contain licorice, this must be kept in mind as a cause of hypokalemia in cancer patients.
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PMID:A hidden cause of hypokalemic paralysis in a patient with prostate cancer. 1535 80

To explore the effects of decreased amounts or absence of aldosterone, we have disrupted the gene coding for aldosterone synthase (AS) in mice and investigated blood pressure and kidney function in AS+/+, AS+/-, and AS-/- mice. AS+/- mice have normal blood pressures and show no abnormalities in electrolytes or kidney gene expression, but they have significantly higher than normal urine volume and lower urine osmolality. In contrast, the AS-/- mice have low blood pressure, abnormal electrolyte homeostasis (increased plasma concentrations of K+, Ca2+, and Mg2+ and decreased concentrations of HCO3(-) and Cl- but no difference in the plasma Na+ level), and disturbances in water metabolism (higher urine output, decreased urine osmolality, and impaired urine concentrating and diluting ability). Absence of aldosterone in the AS-/- mice induced several compensatory changes: an increased food intake-to-body weight ratio, an elevated plasma concentration of glucocorticoids, and strong activation of the renin-angiotensin system. Parallel with the markedly increased synthesis and release of renin, the AS-/- mice showed increased expression of cyclooxygenase-2 (COX-2) in macula densa. On salt supplementation, plasma electrolyte concentrations and kidney renin and COX-2 levels became similar to those of wild-type mice, but the lower blood pressure of the AS-/- mice was not corrected. Thus absence of aldosterone in AS-/- mice results in impairment of Na+ reabsorption in the distal nephron, decreased blood pressure, and strong renin-angiotensin system activation. Our data show the substantial correction of these abnormalities, except the low blood pressure, by high dietary salt does not depend on aldosterone.
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PMID:Kidney function in mice lacking aldosterone. 1611 90

Recent study demonstrated that duodenal HCO3- secretion is affected by modulation of the renin-angiotensin system. We examined the effects of enalapril (angiotensin-converting enzyme (ACE) inhibitor) or losartan (angiotensin AT1 receptor antagonist) on duodenal HCO3- secretion in rats and investigated the mechanisms involved in the renin-angiotensin system-related HCO3- response. A proximal duodenal loop was perfused with saline, and HCO3- secretion was measured at pH 7.0 using a pH-stat method and by adding 2 mM HCl. Enalapril increased the HCO3- secretion in a dose-dependent manner, with a decrease in arterial blood pressure (MBP), and these effects were significantly attenuated by pretreatment with indomethacin, L-NAME and FR172357 (a selective bradykinin B2 receptor antagonist). Although losartan alone did not affect the HCO3- secretion, despite reducing MBP, the agent dose-dependently increased the HCO3- secretion in the presence of angiotensin II, and this response was totally antagonized by prior administration of FR172357, indomethacin and L-NAME. Bradykinin also dose-dependently increased the HCO3- secretion with no change in MBP, though transient, and again the effects were blocked by indomethacin, L-NAME and FR172357. Both prostaglandin (PG) E2 and the nitric oxide (NO) donor NOR-3 also increased the HCO3- secretion, the latter effect being inhibited by indomethacin. These results suggest that both an ACE inhibitor and AT1 antagonist (in the presence of angiotensin II) increase duodenal HCO3- secretion via a common pathway, involving bradykinin, NO and PGs. It is also assumed that bradykinin releases NO locally, which in turns stimulates HCO3- secretion mediated by PGs.
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PMID:ACE inhibitor and AT1 antagonist stimulate duodenal HCO3- secretion mediated by a common pathway - involvement of PG, NO and bradykinin. 1620 62

Elevated pH and elevated plasma bicarbonate level above normal characterise metabolic alkalosis. When bicarbonate is elevated pCO2 must also be elevated to maintain pH to its normal range. Therefore with metabolic alkalosis, the compensation is to decrease alveolar ventilation, and increase pCO2. The causes of metabolic alkalosis are gastro-intestinal hydrogen and chloride loss and due to renal cause. For metabolic alkalosis to continue both generation and maintenance of high levels of bicarbonate are necessary. The diagnosis of metabolic alkalosis is established by noting pH, serum bicarbonate (elevated) and pCO2 (compensatory) elevation. To establish the causes it is necessary to determine intravascular volume, supine and standing blood pressure and renin angiotension alolosterone axis. In chloride responsive alkalosis in which the conditions are extracellular volume depletion, hypokalaemia and hypochloraemia correction of intravascular volume with sodium chloride is needed. In severe metabolic alkalosis of any cause dilute hydrochloric acid (0.1 N HCl) may be infused intravenously but haemolysis may be a complication. In emergency situation with severe hypokalaemia dialysis with higher K+, Cl- and low HCO3- bath will be appropriate.
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PMID:Diagnosis and management of metabolic alkalosis. 1744 63

Pendrin is expressed in the apical regions of type B and non-A, non-B intercalated cells, where it mediates Cl(-) absorption and HCO3(-) secretion through apical Cl(-)/HCO3(-) exchange. Since pendrin is a robust I(-) transporter, we asked whether pendrin is upregulated with dietary I(-) restriction and whether it modulates I(-) balance. Thus I(-) balance was determined in pendrin null and in wild-type mice. Pendrin abundance was evaluated with immunoblots, immunohistochemistry, and immunogold cytochemistry with morphometric analysis. While pendrin abundance was unchanged when dietary I(-) intake was varied over the physiological range, I(-) balance differed in pendrin null and in wild-type mice. Serum I(-) was lower, while I(-) excretion was higher in pendrin null relative to wild-type mice, consistent with a role of pendrin in renal I(-) absorption. Increased H2O intake enhanced differences between wild-type and pendrin null mice in I(-) balance, suggesting that H2O intake modulates pendrin abundance. Raising water intake from approximately 4 to approximately 11 ml/day increased the ratio of B cell apical plasma membrane to cytoplasm pendrin label by 75%, although circulating renin, aldosterone, and serum osmolality were unchanged. Further studies asked whether H2O intake modulates pendrin through the action of AVP. We observed that H2O intake modulated pendrin abundance even when circulating vasopressin levels were clamped. We conclude that H2O intake modulates pendrin abundance, although not likely through a direct, type 2 vasopressin receptor-dependent mechanism. As water intake rises, pendrin becomes increasingly critical in the maintenance of Cl(-) and I(-) balance.
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PMID:Role of pendrin in iodide balance: going with the flow. 1960 45

Potassium (K+) is a key component of the resting membrane potential of all cells that influences many important biologic events. The clinical importance of K+ is that surpluses or deficits in K+ in the extracellular fluid may predispose the patient to cardiac arrhythmias. The kidneys adjust overall K+ homeostasis by increasing or decreasing the rate of excretion of K+. Urinary excretion of K+ has 2 components: (i) the concentration of K+ in the tubular fluid that depends on the capacity of the cortical collecting duct to secrete K+. The capacity is determined by the lumen-negative transepithelial potential difference generated by the electrogenic reabsorption of Na+. Aldosterone and to a lesser degree HCO3- and Na+ in the tubular fluid are implicated in the generation of the potential difference. This component is evaluated by the transtubular K+ gradient (TTKG). (ii) The volume of fluid delivered to the cortical collecting duct that depends on the osmolar rate of excretion. These 2 components can be calculated if blood osmolality is higher than urine osmolality. Thus, investigating K+ abnormalities is based on the determination of TTKG and osmolar rate of excretion in the cortical collecting duct, on other clinical (extracellular fluid, blood pressure...) and biological data (24-hour K+ excretion, renin, aldosterone...) easily available. First treatment of K+ abnormality is the treatment of its cause. Insulin and glucose supply and dialysis are the best symptomatic treatments of hyperkalaemia.
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PMID:[Potassium physiology, hypokalaemia and hyperkalaemia]. 2039 66


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