A 54-year-old woman with diabetes mellitus was hospitalized with generalized edema and weakness. She was also found to have hypertension, hypokalemia and metabolic alkalosis. Detailed examination showed subnormal plasma renin activity and plasma aldosterone concentration. Adrenal CT scanning revealed no adrenal tumor. A successful treatment with amiloride established the diagnosis of Liddle's syndrome for the patient. Liddle's syndrome, a rare hereditary disease usually found in young patients, should be considered in the differential diagnosis of hypertension even in elderly individuals.
Aldosterone/deficiency* ; Aldosterone/blood ; Alkalosis/genetics* ; Case Report ; Female ; Human ; Hypertension/etiology ; Hypokalemia/genetics* ; Middle Age ; Renin/deficiency* ; Renin/blood ; Syndrome

BACKGROUND AND OBJECTIVES: Previous studies reported that sodium and potassium play an important role in the pathogenesis of hypertension. Recently attention has been directed towards a possible role of the divalent cations such as calcium, and magnesium. Plasma renin activity is also known to be related to divalent cations heterogeneously. This study investigated the relationships between serum magnesium and ionized calcium and plasma renin activity. MATERIALS AND METHODS: The subjects consisted of 27 essential hypertensive patients and 25 normotensive controls. Criteria for hypertensive group in this study were systolic blood pressure> or =140mmHg or a diastolic blood pressure > or =90mmHg (JNC-VI, 1997). Inclusion criteria were normal urinalysis, no history of systemic illness, no intake of antihypertensive drugs, and no recent intake of any other medication. We took magnesium-loading test for a reliable method of assessing possible magnesium deficiency. RESULTS: There was no significant difference between two groups in serum Magnesium concentration and other electrolytes and plasma renin activity. There was significantly higher rate in hypertensives than in normotensives in magnesium retention(hypertensive vs. normotensive: 63.56+/-12.21% vs. 38.43+/-11.53%, P<0.001). There was significant differences in ionized calcium between high-renin and low-or normo-renin hypertensives(P<0.001). Plasma renin activity was correlated positively with serum ionized calcium in hypertensives(r=.8147; P<0.001). CONCLUSION: These results suggest that plasma renin activity is a factor that can influence on serum ionized calcium in high-renin hypertensives.
Antihypertensive Agents ; Blood Pressure ; Calcium* ; Cations, Divalent ; Electrolytes ; Humans ; Hypertension ; Magnesium Deficiency ; Magnesium* ; Plasma* ; Potassium ; Renin* ; Sodium ; Urinalysis

BACKGROUND AND OBJECTIVES: Previous studies reported that sodium and potassium play an important role in the pathogenesis of hypertension. Recently attention has been directed towards a possible role of the divalent cations such as calcium, and magnesium. Plasma renin activity is also known to be related to divalent cations heterogeneously. This study investigated the relationships between serum magnesium and ionized calcium and plasma renin activity. MATERIALS AND METHODS: The subjects consisted of 27 essential hypertensive patients and 25 normotensive controls. Criteria for hypertensive group in this study were systolic blood pressure> or =140mmHg or a diastolic blood pressure > or =90mmHg (JNC-VI, 1997). Inclusion criteria were normal urinalysis, no history of systemic illness, no intake of antihypertensive drugs, and no recent intake of any other medication. We took magnesium-loading test for a reliable method of assessing possible magnesium deficiency. RESULTS: There was no significant difference between two groups in serum Magnesium concentration and other electrolytes and plasma renin activity. There was significantly higher rate in hypertensives than in normotensives in magnesium retention(hypertensive vs. normotensive: 63.56+/-12.21% vs. 38.43+/-11.53%, P<0.001). There was significant differences in ionized calcium between high-renin and low-or normo-renin hypertensives(P<0.001). Plasma renin activity was correlated positively with serum ionized calcium in hypertensives(r=.8147; P<0.001). CONCLUSION: These results suggest that plasma renin activity is a factor that can influence on serum ionized calcium in high-renin hypertensives.
Antihypertensive Agents ; Blood Pressure ; Calcium* ; Cations, Divalent ; Electrolytes ; Humans ; Hypertension ; Magnesium Deficiency ; Magnesium* ; Plasma* ; Potassium ; Renin* ; Sodium ; Urinalysis

Osteopontin (OPN) is a secreted phosphoprotein that is constitutively expressed in the normal kidney and is induced by various experimental and pathologic conditions. Several possible functions of OPN have been suggested, however the mechanism and significance of OPN expression are still uncertain. Since high salt concentration or salt crystal have been known to enhance OPN expression in intact kidney or cultured renal cells, in the present study we examined whether or not a low salt condition had an effect on OPN expression in the kidney. Adult male Sprague-Dawley rats were fed either a normal sodium or a sodium deficient diet for 1 week. Kidneys were processed for in situ hybridization using a digoxigenin-labeled riboprobe and for immunohistochemistry using antibodies to OPN, renin, and Na-K-ATPase. In rats fed a normal sodium diet, OPN mRNA and protein were expressed only in the descending thin limbs of Henle's loop (DTL) and in the papillary and pelvic surface epithelium (PSE). In rats fed a sodium deficient diet, there was a marked decrease in OPN immunoreactivity in the DTL, but no changes in PSE. In contrast, no changes were observed in OPN mRNA expression in the DTL by in situ hybridization, indicating that decreased OPN protein expression was a result of translational regulation. As expected, rats fed a sodium deficient diet were associated with increased immunoreactivity for Na-K-ATPase and renin compatible with activation of the renin-angiotensin system. These results suggest that dietary sodium may be involved in the regulation of OPN expression in the DTL of the rat kidney.
Animal ; Diet, Sodium-Restricted* ; Immunohistochemistry ; In Situ Hybridization ; Kidney/metabolism* ; Male ; Na(+)-K(+)-Exchanging ATPase/metabolism ; Rats ; Rats, Sprague-Dawley ; Renin/metabolism ; Sialoglycoproteins/metabolism ; Sialoglycoproteins/antagonists & inhibitors* ; Sodium/deficiency*

OBJECTIVES: There are many interesting reports suggesting that magnesium(Mg) deficiency is deleterious in patients with congestive heart failure (CHF). It is paradoxical that the most important cause of Mg deficiency in these persons is maybe use of therapeutics including diuretics. Authors investigated the trend of serum and 24 hour urine Mg with other relating electrolytes in Mg homeostasis prospectively, in the management of CHF. And we assessd the effects of medications and many variables in .CHF on serum Mg, and the usefulness of serum Mg representing the body content. METHODS: Fifty three patients who were diagnosed as CHF by clinical finding and echocardiogaphy were prescribed conventional doses of diuretics as furosemide 40mg and spironolactone 50mg daily, with or without angiotensin converting enzyme(ACE) inhibitor and digitalis. And then, serial serum and 24 hour urine Mg, sodium, potassium and calcium were obtained at admission, 2nd day, 5th day, and discharge. RESULTS: The patients group with chronic CHF, which was defined as long-term use of diuretics over 6 months, showed higher prevalence of low level of serum Mg concentration than the group with acute one(11 of 28, 39% vs. 2 of 25. 8%, P< 0.01). Of those two groups, the latter showed upward trend of serum Mg from admission to discharge, but the former showed no change. In 24 hour urine Mg excretion, the amount of the patients with CHF was larger than that of control group. In the chronic CHF group, the effect of digitalis on decreasing serum Mg was evident. Serum Mg of acute CHF group correlated with serum BUN(r=0.5609). Whereas, that of chronic group with ejection fraction(r=-0.4742) and plasma renin activity(r=-0.3791), with serum potassium(r=0.4673) and creatinine(0.5846). Serum Mg may be useful indicator of Mg homeostasis, especially in chronic CHF patients. CONCLUSION: Because patients with chronic CHF were prone to deficiency of Mg in the management, maintaining the adequate serum Mg through long- term replacement seems very important in decreasing the morbidity and mortality of these persons.
Angiotensins ; Calcium ; Digitalis ; Diuretics ; Electrolytes ; Estrogens, Conjugated (USP)* ; Furosemide ; Heart Failure* ; Homeostasis ; Humans ; Magnesium Deficiency ; Magnesium* ; Mortality ; Plasma ; Potassium ; Prevalence ; Prospective Studies ; Renin ; Sodium ; Spironolactone

Vitamin D deficiency is prevalent, primarily due to limited sun exposure, which may be observed in urban areas, or as a result of modern lifestyles. Common myths about vitamin D persist, including that it is mostly obtained from the diet and is only essential for bone and mineral homeostasis. Nonetheless, advances in biomedical science suggest that vitamin D is a hormone that is integral to numerous physiologic functions in most cells and tissues. Therefore, abnormal vitamin D levels may contribute to health disturbances. A number of recent reports on potential associations between vitamin D deficiency and cardiovascular disease have highlighted its role in this system. A focus over the previous decade has been to better understand the mechanisms behind vitamin D regulation and the pathophysiology associated with suboptimal vitamin D levels. Vitamin D deficiency is highly associated with the incidence of cardiovascular diseases, even when considering other well-known risk factors. In this process, the renin-angiotensin system is disrupted, and hypertension and endothelial dysfunction contribute to the risk of cardiovascular disease. Likewise, clinical outcomes upon the normalization of vitamin D levels have been investigated in different patient populations. It makes sense that vitamin D supplementation to improve vitamin D status among vitamin D-deficient individuals could be useful without requiring a sudden lifestyle change. This manuscript provides a brief overview of vitamin D metabolism and the vitamin D receptor. It also summarizes the current clinical research relating to vitamin D supplementation and its effects on hypertension and endothelial dysfunction in cardiovascular medicine.
Blood Pressure* ; Calcitriol ; Cardiovascular Diseases ; Diet ; Homeostasis ; Humans ; Hypertension ; Incidence ; Life Style ; Receptors, Calcitriol ; Renin-Angiotensin System ; Risk Factors ; Solar System ; Vitamin D Deficiency ; Vitamin D* ; Vitamins

Hypokalemia usually reflects total body potassium deficiency, but less commonly results from transcellular potassium redistribution with normal body potassium stores. The differential diagnosis of hypokalemia includes pseudohypokalemia, cellular potassium redistribution, inadequate potassium intake, excessive cutaneous or gastrointestinal potassium loss, and renal potassium wasting. To discriminate excessive renal from extrarenal potassium losses as a cause for hypokalemia, urine potassium concentration or TTKG should be measured. Decreased values are indicative of extrarenal losses or inadequate intake. In contrast, excessive renal potassium losses are expected with increased values. Renal potassium wasting with normal or low blood pressure suggests hypokalemia associated with acidosis, vomiting, tubular disorders or increased renal potassium secretion. In hypokalemia associated with hypertension, plasam renin and aldosterone should be measured to differentiated among hyperreninemic hyperaldosteronism, primary hyperaldosteronism, and mineralocorticoid excess other than aldosterone or target organ activation. Hypokalemia may manifest as weakness, seizure, myalgia, rhabdomyolysis, constipation, ileus, arrhythmia, paresthesias, etc. Therapy for hypokalemia consists of treatment of underlying disease and potassium supplementation. The evaluation of hyperkalemia is also a multistep process. The differential diagnosis of hyperkalemia includes pseudohypokalemia, redistribution, and true hyperkalemia. True hyperkalemia associated with decreased glomerular filtration rate is associated with renal failure or increased body potassium contents. When glomerular filtration rate is above 15 mL/min/1.73m2, plasma renin and aldosterone must be measured to differentiate hyporeninemic hypoaldosteronism, primary aldosteronism, disturbance of aldosterone action or target organ dysfunction. Hyperkalemia can cause arrhythmia, paresthesias, fatigue, etc. Therapy for hyperkalemia consists of administration of calcium gluconate, insulin, beta2 agonist, bicarbonate, furosemide, resin and dialysis. Potassium intake must be restricted and associated drugs should be withdrawn.
Acidosis ; Aldosterone ; Arrhythmias, Cardiac ; Calcium Gluconate ; Constipation ; Diagnosis, Differential ; Dialysis ; Fatigue ; Furosemide ; Glomerular Filtration Rate ; Gluconates ; Hyperaldosteronism ; Hyperkalemia ; Hypertension ; Hypoaldosteronism ; Hypokalemia ; Hypotension ; Ileus ; Insulin ; Paresthesia ; Plasma ; Potassium ; Potassium Deficiency ; Renal Insufficiency ; Renin ; Rhabdomyolysis ; Seizures ; Vomiting

Vitamin D is essential for maintaining calcium and phosphate homeostasis, and vitamin D analogues have been prescribed to treat osteoporosis and hyperparathyroidism. Emerging evidence suggests that cardiovascular and chronic kidney diseases are closely associated with vitamin D deficiency resulting from either decreased sunshine exposure or inadequate intake. Vitamin D is through stimulating vitamin D receptor to form a transcriptional complex with cofactors to modulate approximately 3% gene transcription. For example, renin, matrix metalloprotease, and tumor necrosis factor-α are regulated by vitamin D. Both experimental and clinical studies support the health benefits of vitamin D in the cardiovascular system, and such benefits include protecting cardiac function, lowering blood pressure, improving endothelial function, inhibiting oxidative stress, and reducing the activity of renin-angiotensin system. This article will briefly review the cardiovascular benefits of vitamin D and its bioactive analogues and discuss the novel cellular and molecular mechanisms accounting for cardiovascular protection.
Blood Pressure ; Calcium ; physiology ; Cardiovascular Diseases ; physiopathology ; Cardiovascular Physiological Phenomena ; Endothelium, Vascular ; physiology ; physiopathology ; Humans ; Oxidative Stress ; Receptors, Calcitriol ; physiology ; Renin-Angiotensin System ; Vitamin D ; analogs & derivatives ; physiology ; Vitamin D Deficiency ; physiopathology

BACKGROUND/AIMS: There has been controversy about the role of Toll-like receptor 2 (TLR2) in renal injury following ureteric obstruction. Although inhibition of the renin angiotensin system (RAS) reduces TLR2 expression in mice, the exact relationship between TLR2 and RAS is not known. The aim of this study was to determine whether the RAS modulates TLR2. METHODS: We used 8-week-old male wild type (WT) and TLR2-knockout (KO) mice on a C57Bl/6 background. Unilateral ureteral obstruction (UUO) was induced by complete ligation of the left ureter. Angiotensin (Ang) II (1,000 ng/kg/min) and the direct renin inhibitor aliskiren (25 mg/kg/day) were administrated to mice using an osmotic minipump. Molecular and histologic evaluations were performed. RESULTS: Ang II infusion increased mRNA expression of TLR2 in WT mouse kidneys (p < 0.05). The expression of renin mRNA in TLR2-KO UUO kidneys was significantly higher than that in WT UUO kidneys (p < 0.05). There were no differences in tissue injury score or mRNA expression of monocyte chemotactic protein 1 (MCP-1), osteopontin (OPN), or transforming growth factor beta (TGF-beta) between TLR2-KO UUO and WT UUO kidneys. However, aliskiren decreased the tissue injury score and mRNA expression of TLR2, MCP-1, OPN, and TGF-beta in WT UUO kidneys (p < 0.05). Aliskiren-treated TLR2-KO UUO kidneys showed less kidney injury than aliskiren-treated WT UUO kidneys. CONCLUSIONS: TLR2 deletion induced activation of the RAS in UUO kidneys. Moreover, inhibition of both RAS and TLR2 had an additive ameliorative effect on UUO injury of the kidney.
Amides/*pharmacology ; Angiotensin II/pharmacology ; Animals ; Disease Models, Animal ; Fibrosis ; Fumarates/*pharmacology ; Kidney/*drug effects/metabolism/pathology ; Male ; Mice, Inbred C57BL ; Mice, Knockout ; Nephritis, Interstitial/genetics/metabolism/pathology/*prevention & control ; RNA, Messenger/genetics/metabolism ; Renin/*antagonists & inhibitors/metabolism ; Renin-Angiotensin System/*drug effects ; Toll-Like Receptor 2/deficiency/drug effects/genetics/*metabolism ; Ureteral Obstruction/*drug therapy/genetics/metabolism/pathology