Intralymphocyte free magnesium and plasma triglycerides

To evaluate the relative effect of hypertension and plasma triglycerides on intralymphocyte magnesium we measured ionized intralymphocyte magnesium (Mg(i)) concentration by means of a fluorimetric method based on the dye Furaptra in 4 groups of subjects: 18 normotensive normotriglyceridemic controls (NTNC), 9 hypertriglyceridemic normotensive patients (HTN), 8 hypertriglyceridemic essential hypertensive patients (HTEH), 17 normotriglyceridemic essential hypertensive patients (NTEH). Hypercholesterolemic, diabetic patients and alcoholics were excluded from the study. Mg(i) was found to be statistically reduced (ANOVA test F=10.41, P=0.0001) in both HTN and HTEH (M+/- SD, HTN: 0.235 +/- 0.01, HTEH: 0.236 +/- 0.01 mmol/l) as compared to both NTNC and NTEH (M +/- SD, NTNC: 0.294 +/- 0.008, NTEH: 0.297 +/- 0.009 mmol/l). A statistically significant negative correlation was found in the population as a whole between Mg(i) and plasma triglycerides (n=52, R= -541, P=0.00004). Our data suggest that hypertriglyceridemia per se and possibly the so-called plurimetabolic syndrome is characterized by low intralymphocyte free magnesium.     

T235 variant of the angiotensinogen gene and blood pressure in the Chilean population

BACKGROUND: The angiotensinogen gene has recently been linked to essential hypertension. A variant within this gene, encoding threonine rather than methionine at amino acid position 235, was associated with essential hypertension. However, results of new studies have not confirmed this association, suggesting that ethnic differences may explain the different results. OBJECTIVE: To evaluate whether the T235 variant is associated with a higher incidence of essential hypertension among Hispanics (a group that has scarcely been evaluated) and to determine whether T235 is associated with variations in the plasma renin activity or the serum aldosterone level. PATIENTS AND METHOD: We studied 64 patients with essential hypertension and 62 normotensives, matched for age and sex. We obtained samples for determinations of plasma renin activity, serum aldosterone level and genome DNA from all subjects. The genomic DNA was amplified using the polymerase chain reaction technique and digested by the restriction enzyme streptococcus faecalis (Sfa NI) which cuts M235 only, not T235. RESULTS: The patients with essential hypertension had a higher prevalence of the risk variant T235 (alleles 77/128 = 60.2%) than did the normotensive controls (alleles 65/124 = 52.4%), but the difference was not statistically significant (chi2=1.53, P=0.22). The plasma renin activity levels in hypertensives were not statistically different for homozygous T235, heterozygous and homozygous M235 (1.0 +/- 0.96, 2.0 +/- 2.25 and 1.55 +/- 1.49 ng/ml per h, respectively, P=0.5 1). However, when we considered those hypertensives with low plasma renin activity levels (< 1 ng/ml per h), we found a high prevalence (72.7%) of subjects homozygous for the T235 variant. We found no association between the T235 variant and the serum aldosterone levels in hypertensive and normotensive subjects. CONCLUSIONS: We demonstrated that there is a high prevalence of T235 variant in our Hispanic population. The slight difference between prevalences of T235 variant among hypertensive and normotensive subjects that we found was not statistically significant and did not permit us to establish an association between T235 variant and essential hypertension. We believe that only studying a larger cohort of subjects could show whether there is a quantitative effect of the T allele on plasma renin activity levels.     

Insulin resistance and essential hypertension in Vietnamese subjects

Several epidemiological and experimental studies suggest that essential arterial hypertension is associated with hyperinsulinism and insulin resistance in obese subjects and also in subjects with normal body weight. Undernutrition remains frequent in adult Vietnamese people and mean body mass index is around 18.5 kg/m2 in Vietnam. The aim of this study was to look for insulin resistance in hypertensive Vietnamese subjects, despite a markedly lower BMI in Vietnam than in occidental countries. One hundred and eight hypertensive patients (51 men and 57 women) over 40 years (mean = 65.4 years) were compared with 36 healthy subjects (23 men and 13 women) over 40 years (mean = 63.8 years). Hypertensive patients had significantly higher BMI (20.5 +/- 0.3 (SEM) kg/m2 vs 18.4 +/- 0.4 kg/m2; p < 0.01), thicker triceps skinfold (1.26 +/- 0.07 cm vs 0.71 +/- 0.07 cm; p < 0.001) and not significantly different waist/hip ratio (0.88 +/- 0.01 vs 0.85 +/- 0.01). Blood glucose at fasting and 2 hours after 75 g glucose taken orally were similar in hypertensive and normotensive subjects. Plasma insulin at fasting and 2 hours after glucose were significantly higher in hypertensive patients (44.4 +/- 5.1 pmol/L vs 21.6 +/- 3.2 pmol/L; p < 0.05 and 271.1 +/- 21.6 pmol/L vs 139.1 +/- 15.2 pmol/L; p < 0.001). Thus, despite under-nutrition, hypertensive Vietnamese patients have a moderate but significant increase in BMI and fat mass without predominant abdominal localization, and a state of insulin-resistance, compared with normotensive healthy subjects.     

Effect of fluoxetine on the plasma concentrations of clozapine and its major metabolites in patients with schizophrenia

Triglyceride levels and free fatty acid metabolism are influenced by body fat distribution. To test whether the pattern of fat distribution in obese subjects results in distinct insulin mediated suppression of non-esterified fatty acids which could account for differences in plasma triglycerides, we studied 59 obese subjects who were classified according to waist-to-hip ratio. Non-esterified fatty acids and insulin response to a 75 g oral glucose tolerance test were higher in abdominal obesity. Total non-esterified fatty acids response, after adjustment for sex, showed a positive association with waist-to hip ratio (r = 0.292; p < 0.05). The abdominal obese group had higher fasting triglycerides (1.74+/-0.83 versus 1.11+/-0.71 mmol/L; p = 0.003) and lower glucose/insulin ratio (5.2+/-2.3 versus 7.1+/-2.4; p = 0.003). Stepwise multiple regression analysis showed that triglyceride levels are explained by fasting and 120 min non-esterified fatty acids and by glucose/insulin ratio. We conclude that abdominal obesity is associated with a higher resistance to insulin mediated suppression of non-esterified fatty acids in obese subjects. Variation of triglyceride concentrations in obesity is dependent on both fasting and 120 min non-esterified fatty acids as well as on insulin sensitivity to glucose utilization.     

Altered ionic effects of insulin in hypertension: role of basal ion levels in determining cellular responsiveness

To investigate the ionic actions of insulin in hypertension, 19F- and 31P-nuclear magnetic resonance spectroscopy were used to measure cytosolic free calcium (Ca(i)) and intracellular free magnesium (Mg(i)) levels in red blood cells from normal (n = 9) and hypertensive (n = 9) subjects before and 30, 60, 120, and 180 min after in vitro incubation with insulin. In hypertensive patients, basal Ca(i) levels were significantly higher (30.0 +/- 2.2 vs. 19.8 +/- 2.5 nmol/L; P < 0.05), and basal Mg(i) levels were significantly lower (170 +/- 10.9 vs. 209 +/- 8 micromol/L; P < 0.05) than in normotensive subjects. In normal cells, insulin significantly elevated Ca(i) to 39.8 +/- 8.0, 50.1 +/- 8.2, 69.3 +/- 11.1, and 50.9 +/- 13.4 nmol/L at 30, 60, 120, and 180 min and Mg(i) to 238 +/- 10,264 +/- 14,226 +/- 11, and 216 +/- 10 micromol/L at 30, 60, 120, and 180 min. In hypertensive subjects, the insulin-dependent Ca(i) elevation was blunted, and Mg(i) accumulation was completely suppressed. Continuous relationships were observed between basal values of each ion and insulin responses; the greater the Ca(i), the less the Ca(i) rose (r = -0.574; P = 0.013), and the lower the Mg(i), the less Mg(i) rose (r = 0.524; P = 0.025). Furthermore, a blunting of Mg(i) responses to insulin could be reproduced in normal cells that were magnesium depleted by prior treatment either with A23187 in a calcium-free medium or with high glucose concentrations (15 mmol/L). Once again, insulin responsiveness followed basal Mg(i) levels (r = 0.637; P < 0.001). Together, these data demonstrate ionic aspects of insulin resistance in hypertension and suggest that Ca(i) and Mg(i) levels may regulate cellular responsiveness to insulin. This may help to explain the different vascular actions attributed to insulin in normal compared with insulin-resistant states such as hypertension.     

Adrenomedullary secretion of epinephrine is increased in mild essential hypertension

To assess whether patients with mild essential hypertension have excessive activities of the sympathoneuronal and adrenomedullary systems, we examined total body and forearm spillovers and norepinephrine and epinephrine clearances in 47 subjects with mild essential hypertension (25 men, 22 women, aged 38.1 +/- 6.7 years) and 43 normotensive subjects (19 men, 24 women, aged 36.5 +/- 5.9 years). The isotope dilution method with infusions of tritiated norepinephrine and epinephrine was used at rest and during sympathetic stimulation by lower body negative pressure at -15 and -40 mm Hg. Hypertensive subjects had a higher arterial plasma epinephrine concentration (0.20 +/- 0.01 nmol.L-1: mean +/- SE) than normotensive subjects (0.15 +/- 0.01) (P < .01). The increased arterial plasma epinephrine levels appeared to be due to a higher total body epinephrine spillover rate in the hypertensive subjects (0.23 +/- 0.02 nmol.min-1.m-2) than the normotensive subjects (0.18 +/- 0.01) (P < .05) and not to a decreased plasma clearance of epinephrine. The arterial plasma norepinephrine level, total body and forearm norepinephrine spillover rates, and plasma norepinephrine clearance were not altered in the hypertensive subjects. The responses of the catecholamine kinetic variables to lower body negative pressure were not consistently different between normotensive and hypertensive individuals. These data indicate that individuals with mild essential hypertension (1) have elevated arterial plasma epinephrine concentrations that are due to an increased total body epinephrine spillover rate, indicating an increased adrenomedullary secretion of epinephrine; (2) have no increased generalized sympathoneuronal activity and no increased forearm norepinephrine spillover; and (3) have similar responses of both the sympathoneuronal and adrenomedullary systems to sympathetic stimulation by lower body negative pressure.     

Magnesium responsiveness to insulin and insulin-like growth factor I in erythrocytes from normotensive and hypertensive subjects

Depletion of intracellular free magnesium (Mg(i)) is a characteristic feature of insulin resistance in essential hypertension, but it is not clear to what extent low Mg(i) levels contribute to insulin resistance, result from it, or both. As insulin-like growth factor I (IGF-I) may improve insulin resistance, we investigated whether this peptide could similarly improve Mg(i) responsiveness to insulin in hypertension, and whether this effect was related to any direct IGF-I effect on Mg(i). 31P-Nuclear magnetic resonance spectroscopy was used to measure Mg(i) in erythrocytes from 13 fasting normotensive and 10 essential hypertensive subjects before and 30, 60, and 120 min after incubation with a physiologically maximal dose of insulin (200 microU/mL) and with different doses of recombinant human IGF-I (0.1-100 nmol/L). In normotensive subjects, IGF-I elevated Mg(i) (P < 0.05) in a dose- and time-dependent fashion, as did insulin (P < 0.05). However, in hypertensive subjects, maximal Mg(i) responses to insulin, but not to IGF-I, were blunted [insulin, 163+/-11 to 177+/-10 micromol/L (P=NS); IGF-I, 164+/-6 to 190+/-11.7 micromol/L (P < 0.05)]. Furthermore, for insulin, but not for IGF-I, cellular Mg(i) responsiveness was closely and directly related to basal Mg(i) levels (insulin: r=0.72; P < 0.01; IGF-I: r=0.18; P=NS). Lastly, blunted Mg(i) responses to insulin could be reversed by preincubation of hypertensive cells with IGF-I. We conclude that 1) both IGF-I and insulin stimulate erythrocyte Mg(i) levels; 2) cellular Mg(i) responses to insulin, but not to IGF-I, depend on basal Mg(i) levels, i.e. the higher the Mg(i) the greater the sensitivity to insulin; and 3) IGF-I potentiates insulin-induced stimulation of Mg(i) at doses that themselves do not raise Mg(i). These effects of IGF-I may underlie at least in part its ability to improve insulin sensitivity clinically. Together, these data support a role for IGF-I in cellular magnesium metabolism and emphasize the importance of magnesium as a determinant of insulin action.     

Altered cellular calcium responsiveness to insulin in normal and hypertensive pregnancy

OBJECTIVE: To investigate the glucose-independent calcium-related effects of insulin from subjects with normal and hypertensive pregnancies. METHOD: We used lndo-l fluorescence spectroscopy to measure cytosolic free calcium levels (Cai) in peripheral blood mononuclear cells (PBM) from 17 women (aged 20-40 years), six nonpregnant controls (NPC), five pregnant normotensive (PNT) women and six pregnant hypertensive (PHT) women, before and 5, 30, 60, 120 and 180 min after in vitro incubation with 200 microU/ml insulin. RESULTS: Basal Cai levels were significantly higher in PHT women (175.2 +/- 18.8 nmol/l) than they were in NPC women (122.8 +/- 2.8 nmol/l) and PNT women (123.9 +/- 3.5 nmol/l). The initial insulin-induced rise in Cai was similar in NPC (delta Cai 13.5 +/- 5.6 nmol/l) and PNT women (delta Cai 14.6 +/- 3.7 nmol/l), but appeared blunted in PHT women (delta Cai 8.2 +/- 3.5 nmol/l), and, for all pregnant subjects, was closely and inversely related to basal Cai. Over time, in PNT women, delta Cai did not increase from the initial response (maximal delta Cai 20.5 +/- 2.3 nmol/l) compared to NPC. The total cellular calcium response to insulin was also blunted in PNT women (the area under the calcium-responses curve was 86 +/- 3.4 versus 97.4 +/- 6.5 nmol/l), but was excessive in PHT women (115.5 +/- 6 nmol/l, P = 0.05). CONCLUSIONS: Hypertension in pregnancy is associated with excess Cai, insulin raises Cai in PBM, and different alterations of Cai responsiveness to insulin occur both in normal and in hypertensive pregnancy. These cellular calcium alterations may help to explain altered tissue responsiveness to insulin and other hormones in pregnancy.     

Reduced renal sodium excretion in primary hypertensive patients after an oral glucose load

This study was designed to determine urinary sodium excretion in response to an oral glucose load in hypertensive patients. Fifteen hypertensive patients and eighteen normotensive subjects were studied after an overnight fast and for 4 h after the ingestion of 100 g glucose. A subgroup of untreated, nonobese, primary hypertensive patients (five of the 15 hypertensive patients) became hyperinsulinemic (total area under the insulin curve [TAUC]: 33,080 +/- 3348 microU ml(-1) 120 min-1) in response to an oral glucose load compared to normotensive subjects (TAUC: 3670 < 13.731 < 23,693 microU ml(-1) 120 min-1) or to be other subgroup of normoinsulinemic hypertensive individuals TAUC: 10,221 +/- 1615 microU ml-1 120 min-1) despite a similar serum glucose concentration in both groups. A significant decrease in renal sodium excretion in the entire hypertensive group (47.1 +/- 4.7%, P < 0.019) compared to the normotensive (20.0 +/- 10.5%) subjects was also observed during the oral glucose tolerance test. Decreased renal sodium excretion was followed by a transient increase in urinary acid excretion. We speculate that the increase in insulin secretion may be responsible for the sodium-dependent increase in intracellular Ca2+, cellular H+ output and blood pressure in a subgroup of salt-sensitive patients with hypertension. New studies should be designed to identify the precise mechanisms involved in the interaction between hypertension, serum insulin-glucose levels and the magnitude of the renal tubule reabsorption abnormality.     

Insulin sensitivity in familial hypercholesterolemia

Insulin resistance is found in association with obesity, non-insulin-dependent diabetes mellitus, and essential hypertension, which are all risk factors for atherosclerotic cardiovascular disease. Furthermore, hyperinsulinemia has been reported in familial combined hyperlipoproteinemia and endogenous hypertriglyceridemia. Finally, relatively high serum triglyceride and low high-density lipoprotein (HDL) cholesterol concentrations invariably accompany hyperinsulinemia. Whether insulin sensitivity is affected by the isolated presence of high levels of serum low-density lipoprotein (LDL) cholesterol has not been clearly established. We studied 13 subjects with heterozygous familial hypercholesterolemia (FHC) and 15 normocholesterolemic subjects selected to be free of any other known cause of insulin resistance. Thus FHC patients and controls had normal body weight and fat distribution, glucose tolerance, blood pressure, and serum triglyceride and HDL cholesterol concentrations, but were completely separated on plasma LDL cholesterol concentrations (6.05 +/- 0.38 v 3.27 +/- 0.15 mmol/L, P < .0001). Fasting plasma levels of glucose, insulin, free fatty acids (FFA), and potassium and fasting rates of net carbohydrate and lipid oxidation were superimposable in the two study groups. During a 2-hour euglycemic (approximately 5 mmol/L) hyperinsulinemic (approximately 340 pmol/L) clamp, whole-body glucose disposal rates averaged 30.4 +/- 2.3 and 31.1 +/- 3.0 mumol.kg-1 x min-1 in FHC and control subjects, respectively (P = 0.88). The ability of exogenous hyperinsulinemia to stimulate carbohydrate oxidation and energy expenditure and suppress lipid oxidation and plasma FFA and potassium levels was equivalent in FHC and control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Impaired cortisol binding to glucocorticoid receptors in hypertensive patients

We compared glucocorticoid receptor binding characteristics and glucocorticoid responsiveness of human mononuclear leukocytes (HML) from hypertensive patients and matched normotensive volunteers. We also considered associations of these variables with plasma renin activity, aldosterone, cortisol, corticotropin, and electrolyte concentrations. We calculated binding affinity (Kd; nmol/L) and capacity (Bmax; sites/cell) for dexamethasone and cortisol from homologous and heterologous competition curves for specific [3H]dexamethasone binding sites on HML isolated from the blood of normotensive volunteers and subjects with essential hypertension. Glucocorticoid responsiveness of HML was evaluated as IC50 values (nmol/L) for dexamethasone and cortisol for the inhibition of lysozyme release. We measured plasma hormones by radioimmunoassay. Kd values (mean+/-SE) for cortisol in HML of hypertensive patients were higher than in control subjects (24.6+/-2.4 versus 17.5+/-1.7 nmol/L, P<.04). Binding capacity (4978+/-391 versus 4131+/-321 sites/cell), Kd values for dexamethasone (6.7+/-0.5 versus 5.7+/-0.3 nmol/L), and IC50 values for dexamethasone (3.4+/-0.3 versus 3.1+/-0.2 nmol/L) and cortisol (12.2+/-1.6 versus 9.5+/-0.3 nmol/L) were not significantly different. Patients with renin values less than 0.13 ng angiotensin I/L per second were markedly less sensitive to cortisol than those with higher values. Both Kd (30.3+/-2.5 versus 19.2+/-2.4 nmol/L) and IC50 values (15.5+/-1.8 versus 8.9+/-1.2 nmol/L) for cortisol were significantly higher in patients with lower renin values (P<.03). Other variables, including plasma hormone and electrolyte values and binding characteristics for dexamethasone, were not different. These data suggest that cortisol binding to glucocorticoid receptor is slightly impaired in patients with essential hypertension. In vivo, this could lead to inappropriate binding of cortisol to mineralocorticoid receptors. Hence, decreased sensitivity to cortisol is associated with renin suppression. This hypothesis is supported by evidence of hypertension and low renin activity, which others have described in patients with primary glucocorticoid resistance due to mutations of the glucocorticoid receptor.     

Effect of oral pyridoxine hydrochloride supplementation on arterial blood pressure in patients with essential hypertension

The purpose of this study was to test the effect of vitamin B6 (pyridoxine-HCl, CAS 58-56-0) supplementation on arterial blood pressure in essential hypertension. The trial comprised 9 normotensive subjects (7 men and 2 women, aged between 32-58 years; mean +/- SD, 48 +/- 11) and 20 patients with essential hypertension (16 men and 4 women, aged between 32-69 years; mean +/- SD, 56 +/- 12). The patients were treated during 4 weeks with a single oral dose of pyridoxine (5 mg/kg body weight/day). After a 5-min rest, measurements were made in the supine position. When compared with the normotensive subjects, the hypertensive subject group had a significantly higher systolic and diastolic blood pressure (p < 0.001) and higher level of plasma norepinephrine (NE) (p < 0.01) before pyridoxine treatment. On the other hand, there were no significant differences in plasma epinephrine (E) and heart rates. Treatment of hypertensive patients with pyridoxine significantly reduced systolic (p < 0.01) and diastolic blood pressure (p < 0.005), plasma NE (p < 0.005) and E (p < 0.05) within 4 weeks. However, there was no significant difference in heart rate at the end of pyridoxine treatment. These results indicate a relationship between pyridoxine status and arterial blood pressure in the essential hypertensive patients.     

Schizophrenia and genetics: a review and critique for the psychiatric nurse

OBJECTIVES: To study the role of the LDL receptor in the clearance of chylomicron remnants in humans. DESIGN: Chylomicron remnant clearance was studied in five untreated subjects with heterozygous familial hypercholesterolaemia (FH) and nine normolipidaemic controls, by oral retinyl palmitate-fat loading tests. Fasting plasma triglycerides (TG), which are important determinators of chylomicron and remnant clearance, were not significantly different between FH (1.76+/-0.32 mmol L(-1), mean+/-SEM) and controls (1.26+/-0.18 mmol L(-1). Chylomicrons (Sf > 1000) and their remnants (Sf < 1000) were separated by flotation and their clearance was estimated by calculating the area under the 24 h-retinyl palmitate curve (AUC-RP). The factors determining chylomicron and remnant clearance were studied by univariate and multiple regression analysis. RESULTS: Triglyceride clearance in plasma, Sf > 1000 fractions and Sf < 1000 fractions was not significantly different between FH subjects and controls. In subjects with heterozygous FH, chylomicron remnant clearance was two-fold delayed (AUC-RP, 49.39+/-11.61 h.mg L(-1) compared to controls (27.45+/-3.95 h.mg L(-1); P = 0.048). Moreover, 28.4% higher fasting plasma TG in FH resulted in 44.4% higher areas under the remnant-curves compared to controls. The clearance of chylomicron RP was associated to plasma apo E (beta = 0.73, P = 0.011), plasma LDL cholesterol (beta = 0.62, P = 0.018) and plasma TG (beta = 0.58, P = 0.029). The clearance of remnant RP was associated to the diagnosis (FH vs. non-FH), but not to the well-known determinants of remnant clearance like plasma TG. CONCLUSIONS: The clearance of chylomicrons and large remnants isolated in the Sf > fraction depends primarily on the apo B, E (LDL) receptor and to a lesser extent on plasma triglycerides. The clearance of smaller chylomicron remnants isolated in the Sf < 1000 depends to a large extent on the apo B, E (LDL) receptor.     

Enhanced coronary vasoconstriction in the Syrian myopathic hamster supports the microvascular spasm hypothesis

This study examines the relation between blood pressure and insulin resistance in obese, sedentary middle-aged and older men. Eleven hypertensive and 17 normotensive subjects of comparable age (58.6 +/- 1.0 years, mean +/- SEM), percent body fat (27.7 +/- 0.7%), and maximal aerobic capacity (30.2 +/- 0.9 mL.kg-1.min-1) participated in this study. Glucose disposal (M, milligrams per kilogram of fat-free mass per minute) determined during a three-dose hyperinsulinemic euglycemic clamp was lower in the hypertensive than normotensive subjects at the low (M at 120 pmol/m2.min: 2.3 +/- 0.2 versus 3.2 +/- 0.3, P = .06), intermediate (M at 600 pmol/m2.min: 8.0 +/- 0.6 versus 10.4 +/- 0.6, P = .02), and high (M at 3000 pmol/m2.min: 13.5 +/- 0.5 versus 15.5 +/- 0.7, P = .04) insulin infusion rates. The calculated insulin concentration necessary for a half-maximal effect (EC50) was greater in the hypertensive than normotensive subjects (1164 +/- 168 versus 864 +/- 66 pmol/L, P = .03). In this population of normotensive and hypertensive men, systolic, diastolic, and mean arterial blood pressures were related to glucose disposal at these insulin infusion rates (r = -.35 to -.46, P < .05) as well as the EC50 (r = .42 to .44, P < .05). Thus, hypertensive obese, sedentary older men have a reduction in both sensitivity and maximal responsiveness to insulin that is directly related to the severity of hypertension independent of obesity and physical fitness.     

Depletion of NOS activity in the rat dentate gyrus neurons by DSP-4 and protection by deprenyl

Insulin resistance and hyperinsulinemia have been linked with essential hypertension. Age-associated increases in glucose intolerance and hypertension are also well established. To clarify the influence of aging on the insulin sensitivity, euglycemic hyperinsulinemic glucose clamp technique was carried out in 41 normotensive subjects and 42 patients with essential hypertension. The subjects of these groups were divided into two subgroups: young (< 40 years old) and middle-elderly (> or = 40 years old). Insulin sensitivity was assessed as M-value, the rate at which glucose must be infused to maintain a basal blood glucose level. In normotensive subjects, the young subgroup had a significantly higher M-value than did the middle-elderly subgroup. There was a significant negative correlation between age and M-value in normotensive subjects. On the other hand, there was no significant difference in M-value between the young and middle-elderly subgroups in the patients with essential hypertension. The age did not correlate with M-value in the hypertensive group. The normotensive subjects showed a significantly lower M-value than the hypertensive patients in the young group, but not in the middle-elderly group. These results indicate that 1) insulin sensitivity declines with age in normotensive subjects and that 2) insulin sensitivity is already diminished in the early stage of hypertension, and no further decrease in insulin sensitivity occurs with aging in essential hypertensive patients.     

Hereditary neuralgic amyotrophy

Using a new ion-selective electrode, plasma concentration of ionized magnesium was measured in nine adult patients undergoing orthotopic liver transplantation. Baseline plasma ionized magnesium (IMg2+) concentration (0.49 +/- 0.07 mmol/L) was slightly below normal values (0.55-0.66 mmol/L, 95% CI): Six patients had ionized hypomagnesemia and two of these had total hypomagnesemia. Ionized IMg2+ concentration progressively decreased during the dissection (0.45 +/- 0.07 mmol/L, p < 0.05) and anhepatic stage (0.38 +/- 0.07 mmol/L, p < 0.05) and returned toward baseline values by 2 hours after graft reperfusion. Plasma ionized calcium levels and acid-base status were maintained within normal limits during surgery. Serum citrate concentration increased during the dissection (0.58 +/- 0.60 mmol/L) and anhepatic stages (1.18 +/- 0.78 mmol/L), the result of transfusion of citrate-rich blood products in the absence of adequate hepatic function, and gradually returned toward baseline values after graft reperfusion. IMg2+ concentration inversely correlated with the plasma citrate concentration (r2 = 0.54). The results of this study demonstrate that ionized hypomagnesemia invariably occurs during liver transplantation and suggest that this derangement may be a clinical concern, because magnesium is an important cofactor for the maintenance of cardiovascular homeostasis. The data further suggest the clinical importance of supplementation with magnesium based on the monitoring of plasma IMg2+ concentration.     

Lipolytic sensitivity and response to fasting in normotensive and hypertensive obese humans

Obese persons with hypertension are at greater risk for diabetes and hyperlipidemia than normotensive obese persons. It has been postulated that increased lipolytic rates contribute to these metabolic diseases. Therefore, we evaluated the glycerol rate of appearance (Ra) in plasma, an index of whole-body lipolytic activity, during basal conditions and during 60 minutes of epinephrine infusion after 12 and 84 hours of fasting in six normotensive (body mass index [BMI], 39.9 +/- 1.8 kg/m2) and six hypertensive (BMI, 38.7 +/- 1.6 kg/m2) obese persons. Basal glycerol Ra was lower in hypertensive than in normotensive subjects at both 12 hours (1.58 +/- 0.21 v 2.27 +/- 0.28 mumol/kg/min, respectively; P < .01) and 84 hours (2.04 +/- 0.06 v 2.50 +/- 0.13 mumol/kg/min, respectively; P < .01) of fasting. Peak glycerol Ra during epinephrine infusion after 84 hours of fasting (5.69 +/- 0.72 and 11.40 +/- 0.78 mumol/kg/min for hypertensive and normotensive subjects, respectively) was significantly greater than at 12 hours (3.09 +/- 0.29 and 5.06 +/- 0.69 mumol/kg/min) in both hypertensive and normotensive subjects. However, peak glycerol Ra was lower in hypertensive than in normotensive subjects after 12 and 84 hours of fasting (P < .01 for 84 hours). We conclude that hypertension in obese persons is associated with a decrease in both basal lipolytic rates and lipolytic sensitivity to epinephrine infusion.     

Influenza A virus lacking the NS1 gene replicates in interferon-deficient systems

Erythrocyte aggregation, which plays an important role in the physiological behavior of blood fluidity, was found to be enhanced in hypertension and hypercholesterolemia. While the role of macromolecule bridging force has been widely described, cellular factors related to membrane sialic acid content, which might contribute to the negative charge of cell surface causing the repulsion of erythrocytes, have been less studied. Cell age-dependent changes in membrane sialic acid content (in micromoles per gram of integral membrane protein) were investigated in 24 normotensive and 24 hypertensive matched subjects, each divided into 2 identical subgroups according to a cutoff of 6.2 mmol/L serum cholesterol. A progressive and significant (P<0.001) decrease in membrane sialic acid content associated with an increase (P<0.001) of disaggregation shear rate threshold (laser reflectometry in the presence of dextran) were observed with increased erythrocyte density (erythrocytes fractionated by density using ultracentrifugation) in both normotensive and hypertensive groups regardless of the cholesterol level. However, disaggregation shear rate threshold was significantly higher and sialic acid content was lower (P<0.001) in both hypertensive and normotensive subjects with hypercholesterolemia compared with either normotensive or hypertensive subjects with low cholesterol, respectively. A high membrane sialic acid content variance, beginning in the younger erythrocytes, was due mainly to triglyceride and LDL cholesterol levels (R2=0.49 for low, R2=0.43 for middle, and R2=0.54 for high densities, ie, young, mean, and senescent erythrocytes, respectively). We conclude that an early decrease in erythrocyte sialic acid content may influence the rheological properties of blood by increasing the adhesive energy of erythrocyte aggregates.     

Glucose intolerance exaggerates left ventricular hypertrophy and dysfunction in essential hypertension

The influence of glucose intolerance, the preclinical stage of diabetes mellitus, on the progression of left ventricular hypertrophy and left ventricular dysfunction in essential hypertension, was assessed with two-dimensional M-mode echocardiography in age- and sex-matched essential hypertensive patients with (n = 28) or without (n = 44) glucose intolerance, and normotensive control subjects (n = 29). Left ventricular mass index in hypertensive patients with glucose intolerance was significantly higher than that in hypertensive patients without glucose intolerance (mean +/- SD, 115.6 +/- 28.2 v 102.1 +/- 22.1 g/m2; P < .05). Left ventricular diastolic function as reflected by peak lengthening rate was reduced in glucose-intolerant hypertensive patients than in hypertensive patients without glucose intolerance (2.68 +/- 0.71 v 3.16 +/- 0.82/sec; P < .05). End-systolic wall stress/left ventricular end-systolic volume index, an index of left ventricular contractility, was reduced more in glucose-intolerant hypertensive patients than in hypertensive patients without glucose intolerance (2.75 +/- 0.55 v 3.13 +/- 0.55 10(3) dyn.m2/cm2.mL-1; P < .01). These findings suggest that glucose intolerance accelerates progression of left ventricular hypertrophy and deteriorates left ventricular diastolic function and contractility in essential hypertension.     

Low-density lipoprotein oxidation and vitamins E and C in sustained and white-coat hypertension

Low-density lipoprotein oxidation and antioxidant vitamins E and C were investigated in white-coat hypertension in comparison with sustained hypertension and normotension. We selected 21 sustained hypertensive subjects, 21 white-coat hypertensive subjects, and 21 normotensive subjects matched for gender, age, and body mass index. White-coat hypertension was defined as clinical hypertension and daytime ambulatory blood pressure <139/90 (subjects were also reclassified using 134/90 and 135/85 mm Hg as cutoff points for daytime blood pressure). Blood samples were drawn for lipid profile determination, assessment of fluorescent products of lipid peroxidation in native LDL, evaluation of susceptibility to LDL oxidation in vitro (lag phase and propagation rate), and determination of LDL vitamin E and plasma vitamins E and C contents. Compared with sustained hypertensive subjects, white-coat hypertensives had significantly lower fluorescent products of lipid peroxidation (15.4+/-3.4 versus 10.2+/-3 units of relative fluorescence/mg LDL protein, P<.05), longer lag phase (54+/-10 versus 88+/-10 minutes, P<.05), lower propagation rate (8.2+/-2.5 versus 5.95+/-2.1 nmol diene/min per mg LDL cholesterol, P<.05), higher LDL vitamin E content (8.3+/-1.1 versus 10.1+/-1.8 nmol/mg LDL cholesterol, P<.05), and plasma vitamin C content (40+/-13 versus 57+9 micromol/L, P<. 05). No significant difference was observed between white-coat hypertensive and normotensive subjects. The results did not change after reclassification of subjects. Our data show that white-coat hypertensive subjects do not show an enhanced propensity to LDL oxidation or reduction in antioxidant vitamins. Given the role of LDL oxidation in the development of atherosclerosis and that of vitamin E and C in protecting against it, these findings suggest that white-coat hypertension per se carries a low atherogenic risk.