Abnormalities of calcium metabolism in essential hypertension

Calcium metabolism has been investigated in patients with essential hypertension and normal renal function to evaluate the renal calcium handling and the reported increase in renal calcium loss. In 55 hypertensive and 55 sex- and age-matched healthy normotensive subjects creatinine clearance, serum total and ionized calcium, plasma parathyroid hormone and 24 h urinary excretion of calcium, sodium and cAMP were measured. In a subgroup of 20 hypertensive patients and 20 controls the fasting calcium excretion rate was also measured. Both 24 h and fasting calcium excretion rates were higher in the hypertensive group; so also were plasma parathyroid hormone and urinary cAMP. Serum total and ionized calcium levels were not different in the two groups. After intravenous calcium infusion (15 mg 3 h-1 kg-1) in seven hypertensive patients and controls, the hypertensive patients excreted more calcium at all serum calcium concentrations. These results support the hypothesis of primary renal calcium leak in essential hypertension. Enhanced urinary calcium excretion rate may cause compensatory parathyroid overactivity.     

Calcium and magnesium in essential hypertension

1. Because disturbances of calcium metabolism have been described in hypertension, measurements of plasma and serum concentrations of ionized calcium, total calcium, magnesium and renin were made in 38 patients with essential hypertension and age- and sex-matched control subjects. Urinary excretion of calcium, magnesium and sodium was also determined. 2. The mean serum concentration of ionized calcium was 1.23 +/- 0.04 (SD) mmol/l in the hypertensive group and 1.21 +/- 0.03 mmol/l in controls, and results were similar after correction for pH. There was a weak positive correlation between serum ionized calcium (pH 7.4) and systolic pressure (r = 0.26, P less than 0.02), but no correlation with plasma renin concentration. 3. Although the difference between serum total calcium concentration in the hypertensive (2.29 +/- 0.09 mmol/l) and control (2.26 +/- 0.07 mmol/l) subjects was not significant, there was a significant correlation between total calcium and systolic pressure (r = 0.23, P less than 0.05) which was maintained after correction for other variables. 4. There were no differences in plasma concentrations of parathyroid hormone or 1,25-dihydroxycholecalciferol between hypertensive and control subjects. 5. The hypertensive group showed higher urinary excretion of calcium (5.9 +/- 3.0 mmol/24 h) than controls (4.6 +/- 1.7 mmol/24 h), but the difference was not maintained after correction for sodium excretion. 6. Serum concentrations of magnesium were similar in the two groups, but urinary excretion of magnesium was significantly lower in hypertensive (3.7 +/- 1.3 mmol/24 h) than control (4.5 +/- 1.6 mmol/24 h) subjects and there was an inverse correlation between magnesium excretion and blood pressure (r = 0.3-0.35, P less than 0.01).     

Changes in aortic elasticity in aged patients with essential arterial hypertension

Aortic elasticity was studied in aged patients with mild and moderate arterial hypertension using magnetic resonance imaging. The analysis of changes in cross section area (CSA) of the ascending aorta in systole has shown that in some patients maximal CSA occurs in different systolic phases while in the other patients CSA remains unchanged. Calculation with the elasticity rate proved that patients with maximal aortic diameter at the beginning of the systole have maximal aortic elasticity while those with minimal changes in aortic diameter in the course of the systole have minimal elasticity. Thus, in aged patients with mild and moderate essential hypertension aortic wall loses its elasticity to different extent. Further studies will specify clinical and pathogenetic implications of reduced aortic elasticity in arterial hypertension.     

Disorders of calcium and magnesium metabolism

Although relatively common, aberrations in divalent cation homeostasis may be overlooked in Emergency Department patients. The intracellular concentration of ionized calcium is the major regulator of cellular function. Patients may present with signs and symptoms of deranged calcium homeostasis that range from the mild and nonspecific to the truly life threatening. Critically ill patients may develop profound, life-threatening hypocalcemia either as a result of their underlying illness or as a complication of resuscitation. Patients with hypercalcemia may present with symptoms that are so vague and nonspecific that the diagnosis may not be considered. An understanding of the pathophysiology of calcium metabolism allows the emergency physician to identify patients at risk for abnormal calcium homeostasis, and to intervene in an appropriate manner. Magnesium is an essential cofactor in a host of important biochemical reactions. Magnesium deficiency is fairly common in certain groups of patients and can cause serious complications. The diagnosis is often difficult to make in the Emergency Department setting. The emergency physician should be aware of clinical situations that predispose to magnesium deficiency and be prepared to institute empiric therapy if indicated. Severe hypermagnesemia is rather uncommonly encountered in the Emergency Department. The magnesium ion is an effective calcium channel blocker, and patients with severe hypermagnesemia develop profound cardiovascular and neuromuscular dysfunction as a result. In pharmacologic doses, magnesium's unique calcium channel antagonism may be clinically useful, and there is growing interest in its potential use as an antiarrhythmic, anticonvulsant, and smooth muscle relaxant.     

Increased erythrocyte magnesium content in essential hypertension

The present study aimed at testing the hypothesis of decreased erythrocyte magnesium content and magnesium deficiency in essential hypertension. Atomic absorption was used to measure the erythrocyte content of total magnesium in 50-year-old otherwise healthy white males with essential hypertension (n = 12, blood pressure (mean +/- SE) 155 +/- 4/109 +/- 2 mmHg) that had never been treated and in normotensive control subjects (n = 12, blood pressure 128 +/- 2/88 +/- 1 mmHg) matched for age, sex, race, height, weight and smoking habits. The erythrocyte magnesium content was significantly increased in the hypertensive group (2.266 +/- 0.063 vs 1.903 +/- 0.069 mmol/l erythrocytes, p less than 0.001). No significant difference between the groups was detected for serum concentration or the 24-h urinary excretion of magnesium. In conclusion, the present study indicates increased rather than decreased erythrocyte content of magnesium in 50-year-old white males with 'never-treated', essential hypertension. Magnesium deficiency is, therefore, unlikely in this subset of critically selected and matched hypertensive patients.     

Changes in calcium metabolic indices during long-term treatment of patients with essential hypertension

1. Disturbances of calcium metabolism, mimicking mild, compensated secondary hyperparathyroidism, accompany essential hypertension, but it is not known whether these alterations are primary or only secondary to the elevated blood pressure. 2. Indices of systemic calcium metabolism were followed prospectively during 6 months' treatment with either propranolol, bendroflumethiazide or verapamil in 35 patients with essential hypertension. Multivariate statistical methods were employed to study the effects of blood pressure reduction upon the metabolic indices with adjustment for the effects of the different antihypertensive agents. 3. Propranolol treatment increased the plasma ionized calcium and serum phosphate concentrations, and reduced the serum levels of parathyroid hormone, free fatty acids and glycerol. Neither the total nor the total albumin-modified serum calcium concentration was significantly affected. Thus, presumably the decrease in free fatty acids reduced the calcium complex and the calcium binding to albumin, and consequently increased the plasma ionized calcium, thereby suppressing the secretion of parathyroid hormone. 4. Bendroflumethiazide caused a reduction of the fasting renal calcium excretion to half the pretreatment level, but produced no other significant changes in the various indices of calcium metabolism. 5. During verapamil treatment, the fasting renal excretion of calcium and magnesium increased, whereas the free fatty acids and glycerol concentrations in serum were reduced. These two changes presumably balanced each other, as the plasma ionized calcium and serum parathyroid hormone concentrations were not significantly altered. 6. There were no consistent relationships between the decrease in blood pressure and the changes in the metabolic indices, either in the total sample or within any subgroup.(ABSTRACT TRUNCATED AT 250 WORDS)     

Impaired insulin-mediated erythrocyte magnesium accumulation in essential hypertension

1. This study was designed to investigate variations in erythrocyte magnesium in the presence of insulin (0.1 unit/l) in hypertensive subjects. 2. Plasma and erythrocyte magnesium levels were found to be significantly lower in hypertensive than in normotensive subjects. 3. The impaired response to insulin (0.1 units/l) of erythrocytes from hypertensive patients was not reversed by elevated extracellular Mg2+ (3.6 mmol/l). 4. Erythrocytes of hypertensive subjects showed an increased membrane microviscosity compared with normotensive subjects. 5. Lidocaine decreased erythrocyte membrane microviscosity and increased erythrocyte magnesium levels in the presence of insulin.     

Urinary calcium excretion in essential hypertension.

Patients with essential hypertension have been reported to have higher levels of urinary calcium excretion (UCaV) than normotensive persons. We tested the hypothesis that the calciuria of hypertension is due to dietary factors and evaluated several alternate mechanisms. UCaV was studied in 15 patients with essential hypertension compared with 16 age- and gender-matched normotensive control subjects. For subjects taking self-selected, free-living diets, the difference in UCaV between normotensive (130 +/- 14 mg/day) and hypertensive subjects (201 +/- 37 mg/day) was not significant (p = 0.1). However, in a controlled diet with moderately restricted sodium intake (88 mEq), urinary calcium excretion was significantly higher (p = 0.02) in the hypertensive than in the normotensive group receiving 400 mg calcium (204 +/- 25 vs 132 +/- 13 mg/day) and 1400 mg calcium (272 +/- 31 vs 187 +/- 25 mg/day). Twenty-four-hour UCaV was directly and significantly correlated with blood pressure (r = 0.63 for standing systolic blood pressure; p < 0.001). A 1000 mg oral calcium load caused similar changes in UCaV (0.12 +/- 0.11 vs 0.12 +/- 0.07 mg per 100 ml glomerular filtration) and serum ionized calcium level (0.06 +/- 0.08 vs 0.06 +/- 0.02 mmol/L) in normotensive and hypertensive subjects, respectively, suggesting that there was no difference in intestinal calcium absorption between the groups. Fasting UCaV did not differ between the hypertensive (8.9 +/- 4.5 mg per 2 hours) and normotensive groups (10.9 +/- 11.5 mg per 2 hours).(ABSTRACT TRUNCATED AT 250 WORDS)     

Renal protection with calcium antagonism in essential hypertension

The natural history of uncontrolled essential hypertension, with respect to renal function, is characterized by a progressive rise in renal vascular resistance, a progressive fall in effective renal plasma flow, and a progressive fall in glomerular filtration rate. Sustained effective antihypertensive therapy may reverse this pathophysiological sequence, preventing the development of arteriolar nephrosclerosis. It is unknown whether such a therapeutic benefit is a nonspecific response to controlling systemic hypertension, or is dependent on controlling both systemic and glomerular hypertension. Recent experimental evidence indicates that the control of systemic blood pressure may not necessarily be associated with control of glomerular capillary hypertension. The renal effects of calcium antagonists in essential hypertensive patients are only now being characterized. We have demonstrated that diltiazem, amlodipine, and nifedipine monotherapies enhance glomerular filtration rate and effective renal plasma flow, and lower renal vascular resistance. Although calcium antagonists attenuate the intrarenal effects of norepinephrine and angiotensin II, the precise mechanism(s) by which these drugs reverse the functional renal abnormalities in the essential hypertensive state, and by which they may attenuate the progression of hypertensive renal disease, are unknown. It is our hypothesis that renal protection requires normalization of both systemic and glomerular capillary pressure. Calcium antagonists have the ability to control systemic hypertension. If they can be demonstrated experimentally to reduce both pre- and post-glomerular capillary resistances (i.e. maintain a normal glomerular capillary pressure), they can be expected to provide long-term renal protection.     

Arteriolar circulation and arterial pressure in patients with essential hypertension

Arteriolar circulation and its relationship with arterial pressure were studied in 127 patients with essential hypertension and 63 healthy subjects using continuous US dopplerography of the microcirculatory system at rest. Linear arteriolar blood flow rate was measured in healthy subjects and 47 patients before and after primary indapamide therapy. It was found to equal 17.7 (mean 9.1) cm/s in systole and 8.7 cm/s in diastole in the patients versus 12.2 (7.3) and 4.3 respectively in the healthy subjects (p = 0.005) giving indirect evidence of narrowed diameter of arterioles. Arteriolar circulation was shown to depend on the duration of arterial hypertension. Both AP and linear arteriolar blood flow rate decreased under effect of hypotensive therapy but there was no significant correlation between the two parameters.     

Long-term treatment of essential arterial hypertension with nitrendipine

The efficacy and safety of long-term treatment with oral nitrendipine were evaluated in 34 patients with essential arterial hypertension. Nitrendipine alone significantly lowered systolic and diastolic blood pressure levels in 28 patients who completed the preliminary four-week dose-setting phase. Twenty-one patients completed the one-year treatment. Blood pressure control was maintained by nitrendipine alone in 11 patients. Ten patients not adequately controlled at the end of the dose-setting phase were successfully treated with nitrendipine combined with acebutolol or muzolimine. It is concluded that nitrendipine is a promising calcium antagonist for the treatment of arterial hypertension.     

Urinary prostaglandin and sodium metabolism in patients with essential hypertension

Urinary prostaglandin E (PGE) excretion as an indicator of renal PGE, urinary aldosterone excretion, plasma renin activity, urinary sodium excretion, and urinary potassium excretion were measured after sodium depletion in 15 patients with essential hypertension to investigate the interaction between renal PGE and sodium metabolism. Following sodium depletion, urinary PGE excretion decreased, whereas urinary aldosterone excretion and plasma renin activity increased. Significant positive correlations were found between urinary PGE excretion and urinary sodium excretion (r=0.41, p less than 0.01) or urinary sodium excretion-urinary potassium excretion ratio (r = 0.43, p less than 0.005). These results support the hypothesis that the renal PGE may play an important role in the regulation of sodium metabolism and this action of PGE is independent of the renin-aldosterone system.     

The membrane-bound calcium of the thrombocytes in essential hypertension

The investigation was aimed at analyzing membrane-bound calcium in platelets of patients with essential hypertension (EH) and of healthy persons. 55 men were examined. Of these, 38 presented with EH and 17 were healthy. Membrane-bound calcium determined with the help of the chlortetracycline fluorescent probe. The level of membrane-bound calcium in intracellular compartments was higher in patients with EH than in the control. The kinetic curves of the binding of the chlortetracycline fluorescent probe with cellular membranes allow one to reveal disturbances of calcium-dependent membrane processes in persons suffering from EH.     

Alpha-1-adrenergic blockade and lipoprotein metabolism in essential hypertension

The effect of the selective alpha 1-antagonist terazosin on serum lipoproteins and certain blood pressure-regulating factors was assessed in 15 patients with essential hypertension. Terazosin given during 8 weeks reduced arterial pressure (from 153/103 +/- 3/2 (SE) to 143/96 +/- 5/2 mm Hg; P less than 0.02) but did not modify body weight, heart rate, blood volume, plasma renin activity, aldosterone and catecholamine levels, or serum cholesterol, triglycerides, and their lipoprotein fractions. In nine of the patients, blood pressure control was not achieved with terazosin monotherapy and the diuretic methyclothiazide, 2.5 mg, was added. After 8 weeks of combined treatment, blood pressure decreased further (P less than 0.05); serum lipids and lipoprotein fractions did not change as compared with placebo or terazosin conditions. These findings indicate that terazosin in monotherapy does not unfavorably influence lipid metabolism.     

Disturbances of calcium and magnesium metabolism occur in most hyperthyroid patients

The concentrations in serum of total and ionised calcium, phosphate, magnesium, albumin and alkaline phosphatase activity were measured in patients when hyperthyroid and again when euthyroid. Significant declines in the mean values of ionised calcium, phosphate and alkaline phosphatase activity and significant increases in the mean concentrations of magnesium and albumin were observed. Similar changes were observed in most individual patients. Levels of ionised calcium greater than two standard deviations (representing between batch imprecision) above the upper limit of the reference range were present in 15.6% of hyperthyroid patients. The hyperthyroid levels of calcium, ionised calcium and alkaline phosphatase activity were highest in patients with the most severe thyrotoxicosis. Disturbances of calcium and magnesium metabolism are frequent in hyperthyroid patients.