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Biomedical subjects

L M Resnick

Publications and source records attributed to L M Resnick.

108 records · Page 6Linked to original sources
PubMed1986

Calcium metabolism in essential hypertension: relationship to altered renin system activity.

Hypertensive disease is associated with various abnormalities of calcium metabolism although how these abnormalities relate to the elevated pressure remains unclear. Based on the use of renin-sodium profiling, we have defined heterogeneous deviations in circulating levels of ionized calcium and magnesium as well as of the calcium-regulating hormones parathyroid hormone, calcitonin, and 1,25-dihydroxyvitamin D (1,25D), which parallel similar deviations in plasma renin activity. Essential hypertensive subjects with a profile of low renin, lower ionized calcium, and elevated 1,25D respond best to the calcium channel blocker nifedipine, demonstrate an enhanced sensitivity to the blood pressure effects of dietary salt loading, and have significantly lower blood pressures in response to oral calcium supplementation. Hypertensive subjects with the opposite metabolic profile--higher renin activity, higher serum ionized calcium, and lower 1,25D levels--are relatively insensitive to the blood pressure effects of either dietary salt loading or nifedipine, and show no significant hypotensive response to calcium supplements. Altogether, these alterations of calcium ionic and hormonal metabolism suggest that the hormonal control of calcium metabolism is linked to renin system activity as well as to the pathophysiology of the hypertensive process.

Calcitonin↗
PubMed1986

Effects of altered dietary calcium intake in experimental hypertension: role of intracellular free magnesium.

Blood pressure, ionic and hormonal effects of high (1.8%) versus low (0.2%) dietary calcium intakes were explored in uninephrectomized DOC-NaCl rats, in two-kidney, one clip (2K, 1C) Goldblatt hypertensive rats and their respective controls. High-calcium diets lowered blood pressure (P less than 0.05) in DOC-NaCl and in control uninephrectomized rats drinking 1% NaCl. However, calcium loading in renin-dependent 2K, 1C rats elevated blood pressure (P less than 0.05) but had no effect in sham-operated controls. Plasma renin activity rose in all animals, while serum ionized calcium rose significantly only in dietary salt-loaded animals. Intracellular free magnesium levels were consistently, inversely linked to blood pressure (r = -0.92, P less than 0.001). This linkage was independent of plasma renin activity, serum ionized calcium values and dietary calcium content. These results demonstrate that the same alteration in dietary mineral content can produce opposite blood pressure effects in different pathophysiological subtypes of hypertensive disease. We conclude that intracellular free magnesium levels directly participate in the final common pathway of events regulating blood pressure and vasoconstrictor tone.

Animals↗
PubMed1985

Renin, calcium metabolism and the pathophysiologic basis of antihypertensive therapy.

The renin-angiotensin-aldosterone system regulates blood pressure and volume homeostasis in addition to sodium and potassium metabolism, and may be linked to divalent cation metabolism as well as hypertensive disease. In essential hypertension, circulating serum magnesium and Ca++, and the calcium regulating hormones, parathyroid hormone, calcitonin and 1,25 dihydroxyvitamin (1,25D) are different in the various renin subgroups. Elevated blood pressure induced by such maneuvers as dietary salt loading is associated with exacerbations of these calcium metabolic deviations, and appears related to salt-induced changes in serum Ca++ or 1,25D levels. Short- or longer-term lowering of blood pressure with the calcium-channel blocker, nifedipine, or with calcium or magnesium supplementation is associated with a shift of renin system activity and calcium metabolic indexes back to average normotensive values in those subjects most susceptible to these hypotensive agents. These observations suggest that deviations in calcium metabolism in essential hypertension may be related to the pathophysiology of the hypertensive process. Further, renin system activity and calcium metabolic indexes such as serum Ca++ levels may help target specific subgroups of hypertensive populations most susceptible to various dietary or drug maneuvers, and thus may provide a basis to better understand and treat clinical hypertension.

Adrenergic beta-Antagonists↗
PubMed1985

Angiotensin I converting enzyme activity in hypertension. Relationship to blood pressure, renin-sodium profiles, and antihypertensive therapy.

The activity of the angiotensin I converting enzyme was measured in 55 patients with untreated essential hypertension, 11 patients with untreated renovascular hypertension, five patients with untreated primary aldosteronism, and 23 normotensive subjects. Converting enzyme activity was significantly higher (p less than 0.025 or less) in essential hypertension (28 +/- 1 units/ml) and renovascular hypertension (28.5 +/- 3 units/ml) when compared with the activity in the normotensive subjects (21 +/- 1.5 units/ml). Seventeen (31 percent) of the patients with essential hypertension and three (27 percent) patients with renovascular hypertension had an elevated converting enzyme activity above the mean +2 standard deviations value of the normotensive subjects (32.8 units/ml), ranging from 33 to 55.8 units/ml. Converting enzyme activity was similar in black and white patients and in male and female patients, but it tended to decrease with increasing age in both the hypertensive and the normotensive subjects. In the untreated patients with essential hypertension (n = 55), converting enzyme activity was inversely related to mean arterial pressure and age (r = -0.34, p less than 0.01) and positively related to plasma renin activity (r = 0.31, p less than 0.05). Converting enzyme activity was always decreased during captopril therapy, and it was not affected by beta blockers, but it was increased by diuretics. These findings indicate that converting enzyme activity is elevated in patients with essential and renovascular hypertension.

Adolescent↗
PubMed1985

Calcium metabolism and parathyroid function in primary aldosteronism.

Calcium and magnesium metabolism was investigated in 10 hypertensive subjects with primary aldosteronism (seven adenomatous, three idiopathic). Serum levels of total calcium (9.03 +/- 0.2 mg/dl) and ionized calcium (2.06 +/- 0.06 meq/liter) were in the low-normal range, except for two patients who had levels of serum ionized calcium clearly above normal. Furthermore, both serum total (n = 6, p less than 0.01) and ionized calcium levels (n = 3) rose postoperatively in the patients who had an aldosterone-producing tumor removed. Dramatic elevations of parathyroid hormone levels (mean, 645 +/- 109 pgeq/liter; normal, less than 150 to 375 pgeq/liter) were seen in the majority of patients, including those two with frank ionized calcium elevations. Magnesium levels were within normal limits (2.07 +/- 0.07 meq/liter). These results indicate that parathyroid hypersecretion is a common feature of primary aldosteronism and also suggest a physiologic relationship between the activity of the renin-aldosterone system and parathyroid physiology. Sodium-volume expansion and negative calcium balance induced by aldosterone excess may predispose to hyperparathyroidism.

Adenoma↗
PubMed1985

Relationship of blood pressure response and the renin-angiotensin system to first-dose prazosin.

It has been reported that the first-dose response to prazosin is more common in patients who are salt-depleted or already receiving beta blockers. The relationship between the first-dose blood pressure and plasma renin responses to oral administration of 1 mg prazosin in 13 (seven male, six female) patients with essential hypertension (average blood pressure = 150/100 +/- 5/2 mm Hg) was studied. Eight of 13 patients experienced marked orthostatic decreases in blood pressure associated with nausea and dizziness. The degree of the orthostatic depressor response was inversely correlated with the baseline plasma renin activity (p less than 0.005). This unique sensitivity of low-renin essential hypertension to prazosin may reflect an underlying increased alpha tone and/or an attendant blunted renin reactivity in this form of human essential hypertension.

Blood Pressure↗
PubMed1985

Calcium metabolism and the renin-aldosterone system in essential hypertension.

Despite recent appreciation of a role for calcium in clinical hypertension, evidence at present is conflicting. Thus, certain studies suggest increased calcium availability may be associated with increased levels of blood pressure, while others suggest that a calcium deficiency may contribute to the pathogenesis of hypertensive disease. Our own group has thus far demonstrated deviations of circulating levels of ionized calcium and of magnesium in essential hypertension, linked with concurrent deviations in the activity of the renal pressor hormone, renin. Furthermore, calcium metabolic indices may predict and even determine dietary sodium sensitivity in hypertension, as well as the blood pressure responsiveness to antihypertensive drug therapy. Moreover, oral calcium supplementation may itself possess antihypertensive actions in specifically targeted renin subgroups of essential hypertensive subjects. Altogether, these results link calcium metabolism, renin system activity, and the pathogenesis of hypertensive disease. It may ultimately be calcium-regulating hormones, which determine cellular disposition of calcium, rather than circulating levels of calcium itself, that mediate the blood pressure and possibly even the renin deviations observed among differing hypertensive individuals.

Aldosterone↗
PubMed1985

The significance of calcium and calcium channel blockade in essential hypertension.

A role for calcium in human hypertensive disease has been suggested. However, the various, apparently contradictory, abnormalities of calcium metabolism observed in experimental and clinical hypertension do not allow for unambiguous description of the specific manner in which calcium contributes to the hypertensive process. We studied calcium metabolism in essential hypertension and used renin-sodium profiling, which reveals the biochemical heterogeneity of clinical hypertension. We observed renin-linked, heterogeneous deviations in circulating levels of the divalent cations, magnesium and ionized calcium, in addition to deviations in the calcium-regulating hormones, parathyroid hormone (PTH), calcitonin (CT), and 1,25 dihydroxyvitamin D (1,25 D). These renin-calcium metabolic deviations may both predict and contribute to the pathophysiology of salt-induced hypertension, the blood pressure effects of oral calcium supplementation, as well as the short and longer term effectiveness of calcium channel blockade. Altogether, these data suggest an intimate linkage between the hormonal control of calcium metabolism, the renin-angiotensin system and blood pressure regulation in human hypertension.

Calcium↗
PubMed1984

Intracellular free magnesium in erythrocytes of essential hypertension: relation to blood pressure and serum divalent cations.

Intracellular levels of free Mg2+ in human erythrocytes were determined by 31P NMR spectroscopy in 26 fasted subjects and were correlated with blood pressures and serum levels of total magnesium (bound and free Mg2+) and ionized calcium from the same subjects in a seated position. Untreated hypertensive individuals consistently demonstrated lower levels of intracellular free magnesium (192 +/- 8 microM, n = 11) than either normotensive (261 +/- 9.8 microM, n = 7, P less than 0.001 vs. untreated hypertensive subjects) or hypertensive subjects whose blood pressure had been normalized on therapy (237 +/- 7.8 microM, n = 8, P less than 0.005 vs. untreated hypertensives). For all subjects, strong relationships existed between intracellular free magnesium and diastolic blood pressure (r = -0.85, P less than 0.001) and systolic blood pressure (r = -0.71, P less than 0.001). Significant relationships also were observed between intracellular free magnesium levels and extracellular serum levels of calcium ion (r = -0.77, P less than 0.001) as well as serum concentrations of total magnesium (r = 0.62, P less than 0.001). We conclude that significant depletion of intracellular free magnesium levels are apparent in erythrocytes of subjects with essential hypertension. Furthermore, the close, inverse relationship of free magnesium levels with the height of the blood pressure suggests that abnormalities of intracellular magnesium metabolism may contribute to the pathophysiology of human essential hypertension.

Blood Pressure↗
PubMed1983

Divalent cations in essential hypertension. Relations between serum ionized calcium, magnesium, and plasma renin activity.

We studied the relation of plasma renin activity to serum levels of ionized calcium and magnesium in 102 normotensive patients and in 98 patients with essential hypertension who were divided into low-renin, normal-renin, and high-renin groups. Serum magnesium levels were higher in patients with low-renin hypertension and lower in patients with high-renin hypertension than in those with normal-renin hypertension (P less than 0.025 for both comparisons) or in normotensive controls (P less than 0.005, P less than 0.05, respectively). In contrast, serum levels of ionized calcium were lower in patients with low-renin hypertension and higher in patients with high-renin hypertension than in those with normal-renin hypertension (P less than 0.001, P less than 0.05, respectively) or in normotensive controls (P less than 0.001, P less than 0.05, respectively). Altogether, the range of plasma renin activity in essential hypertension shows a continuous negative correlation with the serum magnesium level (r = -0.60, P less than 0.001) and a positive correlation with the serum ionized calcium level (r = 0.44, P less than 0.001). Accordingly, plasma renin activity in hypertension may reflect or contribute to changes in calcium and magnesium fluxes across cell membranes.

Calcium↗
PubMed1983

Maternal-fetal immunity: presence of specific cellular hyporesponsiveness and humoral suppressor activity in normal pregnancy and their absence in preeclampsia.

The hypothesis that aberrant maternal-fetal immunity might lead to the development of preeclampsia was examined using mixed lymphocyte culture reactions (MLC) as an in vitro analogue of maternal-fetal immunity. Maternal lymphocytes and serum from five normal pregnant women differed significantly from lymphocytes and serum from five preeclamptics. Maternal cells from normal pregnancy responded appropriately to unrelated control cells, but demonstrated selective hyporesponsiveness to fetal cells in the MLC. Serum from normal pregnancy suppressed MLCs when maternal cells were responder cells (RC) and maternal cells or fetal cells were stimulator cells (SC), and did not inhibit MLCs where maternal cells were RC and control cells were SC. Maternal lymphocytes and serum from preeclamptics did not demonstrate cellular hyporesponsiveness or humoral suppressor activity. Our findings support the notion that specific cellular hyporesponsiveness and humoral suppressor activity is responsible for normal pregnancy; absence of such adaptive immunity might lead to the development of preeclampsia.

Adult↗
PubMed1983

Pheochromocytoma and prazosin.

Prazosin was used to control the signs and symptoms of excessive alpha-adrenergic activity in four patients with pheochromocytomas. Long-term dosage requirements were predicted by the blood pressure response to a single 1-mg oral dose. However, surgical management of the pheochromocytomas was inadequate with prazosin alone, and intravenous phentolamine was required to suppress the pressor surges generated by the tumor during surgical manipulation and excision.

Adult↗
PubMedDate not supplied

Perinatal cellular ion metabolism: 31P-nuclear magnetic resonance spectroscopic analysis of intracellular free magnesium and pH in maternal and cord blood erythrocytes.

OBJECTIVE: We sought to establish and compare the distribution of intracellular and extracellular magnesium and pH in cord and maternal erythrocytes at the time of delivery. METHODS: We used 31P-nuclear magnetic resonance spectroscopy and a magnesium-specific ion-selective electrode apparatus to evaluate plasma and intracellular red cell content of free magnesium, pH, and ionized calcium in blood obtained from cord and corresponding maternal samples. RESULTS: Cord erythrocyte intracellular free magnesium content (110 +/- 4 mumol/L) and pH (7.02 +/- 0.01) were lower than corresponding maternal intracellular values (140 +/- 9 mumol/L, P < .05; and 7.20 +/- 0.02, P < .0005, respectively). The extracellular cord ionized magnesium concentration in plasma was closely related to the intracellular free magnesium concentration (r = 0.71, P < .005). Extracellular ionized magnesium and calcium were both greater in cord than in maternal samples (P < .05 and P < .0005, respectively). CONCLUSION: These data indicate a differential distribution of extracellular and intracellular magnesium and pH in cord versus maternal blood cells. We hypothesize that these deviations are physiological and may serve to maintain tissue oxygen delivery, while at the same time mediating the changes in vascular tone characteristic of birth.

Adult↗