Chronic intravenous glucose infusion causes moderate hypertension in rats

We have reported that chronic insulin infusion increases mean arterial pressure (MAP) in rats. In those studies, glucose was coinfused to prevent hypoglycemia, but it is possible that the glucose infusion rate may have exceeded the rate actually required to prevent hypoglycemia. If true, then the glucose infusion alone should have a similar effect, and this study tested that hypothesis. In six rats (insulin group) instrumented with artery and vein catheters, insulin was infused for 7 days intravenously (iv) at 1.5 mU/kg/min together with glucose iv at 18.6 mg/kg/min. Seven other rats (glucose group) received the same glucose infusion for 7 days but without iv insulin. MAP increased significantly in both groups, from 98 ± 3 and 96 ± 2 mm Hg to 107 ± 5 and 104 ± 3 mm Hg in the insulin and glucose groups, respectively, and the renal and hormonal changes were similar to those previously reported during insulin infusion. There were no significant differences between the two groups for any variable measured. These data indicate that the sugar intake provided by the glucose infusion essentially mimics the response to our insulin and glucose infusion protocol, and that similar mechanisms underlie the renal and cardiovascular responses to each protocol.     

Effect of intravenous enalaprilat in moderate and severe systemic hypertension

The antihypertensive effect and tolerability of enalaprilat, an intravenously administered angiotensin converting enzyme inhibitor, was studied in 65 patients with moderate or severe hypertension. In this randomized, double-blind study, enalaprilat was compared with placebo in 42 (22 enalaprilat, 20 placebo) moderate hypertensive (diastolic blood pressure [BP] 100 to 114 mm Hg) patients. It was compared with furosemide in 23 (12 enalaprilat, 11 furosemide) severe hypertensive (diastolic BP 115 to 130 mm Hg) patients. Enalaprilat (1.25 or 5.0 mg), placebo (5% dextrose) or furosemide (40 or 80 mg) was given every 6 hours intravenously up to 48 hours. In the moderate hypertension stratum, the mean supine diastolic BP was significantly (p less than or equal to 0.01) reduced from baseline at all timepoints in the enalaprilat group. These diastolic BP reductions were significantly (p less than or equal to 0.01) greater in the enalaprilat group than the placebo at 1 to 24 hours (-12 vs -4 mm Hg), with 59% of the patients responding to enalaprilat compared with 30% of the patients responding to placebo. An even greater reduction (p less than or equal to 0.01) was seen at 25 to 48 hours (-14 vs -7 mm Hg, with 73% enalaprilat vs 58% placebo responders). Significant (p less than or equal to 0.01) reductions in mean, supine systolic BP were also seen at 1 to 24 hours (-22 vs -2 mm Hg) and 25 to 48 hours (-24 vs -8 mm Hg) during the 48 hours of the double-blind treatment phase in the enalaprilat group compared with placebo.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of pre-eclampsia on complete blood count, platelet count and mean platelet volume

Pre-eclampsia is a condition observed during pregnancy and threatens the life of both mother and foetus. There are studies, which suggest platelets play a major role in the pathogenesis of pre-eclampsia. The aim of this study is to compare the complete blood count (CBC) parameters, especially platelet count and mean platelet volume (MPV), in pre-eclamptic and normal pregnant women and to evaluate whether these parameters have a prognostic significance in determining the severity of eclampsia. The study and control groups consist of 56 pre-eclamptic and 43 normal pregnant women, respectively. There was no statistically significant difference according to CBC, platelet count and MPV when pre-eclamptic and severely pre-eclamptic patients were compared with controls. As a result, we observed no prognostic significance of CBC, platelet count and MPV on the presence and/or severity of pre-eclamptic condition. There are conflicting results especially on the significance of MPV in the literature, and possibly this confliction is due to the difference between methods and/or equipments used for automated blood count.     

Lymphatic transport pathways during volume expansion

Morphological evidence on lymphatic transport was derived qualitatively and quantitatively in control and volume-expanded rats in order to identify any changes in transendothelial pathways which accompany enhanced lymph formation. Volume expansion was induced by intravenous mannitol and by intraperitoneal hypertonic or hypotonic saline (10% of body wt). Horseradish peroxidase and ferritin were used as macromolecular tracers. Volume expansion had little effect upon intraendothelial cytoplasmic components. Intracytoplasmic vesicles contained tracer molecules in control and experimental groups and quantitative analysis revealed only one significant difference between the groups—a reduction in vesicular volume and numerical densities in animals receiving mannitol. The major changes between control and experimental animals were in the presence of attenuated areas of cytoplasm, widening of intercellular pathways, and the presence of open regions in the expanded group. In these respects there was little qualitative difference among the three experimental groups, although some quantitative differences were recorded. It was concluded that vesicular transport plays a significant role in translymphatic protein movement and that when the interstitial fluid load to lymphatics is increased the excess fluid preferentially enters between adjacent endothelial cells or diffuses across areas of extreme attenuation. Open regions or junctions were considered to play little if any role in lymph formation under control conditions, but to achieve increasing importance with increases in fluid movement.     

The role of additives in allergic vasculitis during intravenous hyperalimentation

A 39-year-old woman who had previously undergone a jejunoileal bypass for morbid obesity was receiving intravenous hyperalimentation. The patient developed allergic vasculitis while receiving fluid which contained a multivitamin solution. Rechallenge with this preparation resulted in an exacerbation of her skin lesions. The possible role of such additives in the development of unusual hypersensitivity reactions is discussed.     

The endocrinology of pre-eclampsia

Pre-eclampsia is a pregnancy specific syndrome that is a principal cause of maternal morbidity and mortality, accounting for almost 15% of pregnancy associated deaths, and is one of the major causes of iatrogenic prematurity among new born babies. The mild form of pre-eclampsia most commonly presents with the features of maternal hypertension and proteinuria, but can swiftly and unpredictably become severe with numerous multisystem complications involving the maternal liver, kidneys, lungs, blood and platelet coagulation and nervous systems. The diverse symptoms of pre-eclampsia have made it a difficult disease not only to define, but also to identify a causative agent for the symptoms. This review examines the complex endocrinological mechanisms believed to be responsible for the extensive complications of pre-eclampsia from the role of placental and endothelial dysfunction, to the causes of the oxidative stress and the ensuing general inflammation. It also highlights current endocrine findings that exhibit the potential for clinical application, as either potential markers or novel therapeutic targets, with the aim of either preventing or altering the course of this life-threatening disease of pregnancy.     

The functions of microparticles in pre-eclampsia

Pre-eclampsia (P-EC), a heterogenic multisystem disorder characterized by hypertension and proteinuria, usually develops in the second half of pregnancy. The incidence is 2 to 5%, and P-EC is therefore a major cause of maternal and perinatal morbidity and mortality. Although the exact etiology is unknown, placental factors released into the maternal circulation lead to systemic maternal inflammation and endothelial dysfunction. Growing evidence indicates that placenta-derived microparticles, best known as syncytiotrophoblast microparticles (STBM), are important among these factors. This review provides an overview of the presence and function(s) of STBM and other cell-derived microparticles and exosomes.     

The role of pharmacotherapy in mild to moderate chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a major health problem worldwide and most of those afflicted have mild to moderate disease as measured by spirometry. There is mounting evidence that even mild airway obstruction is associated with activity-related dyspnea, exercise limitation, impaired quality of life, increased hospitalization and mortality. As our understanding of the complex, heterogeneous pathophysiology and clinical consequences of milder COPD continues to grow, there is increasing interest in the potential impact of therapeutic interventions beyond smoking cessation. Unfortunately, few clinical trials have included patients with mild to moderate disease and the evidence base for pharmacological treatment in this subpopulation is currently lacking. Recent short-term mechanistic studies confirm that reversal of airway smooth muscle cholinergic tone consistently improves respiratory mechanics during rest and exercise in mild COPD but long-term clinical benefits remain to be evaluated. Secondary analysis of large, prospective studies designed to evaluate the efficacy of long-acting bronchodilators, inhaled corticosteroids and combination therapy indicate that patients with moderate COPD achieve comparable benefits to those with advanced disease. In the absence of evidence-based guidelines for the management of milder COPD, treatment choices are driven mainly by clinical presentation: for those with persistent and troublesome activity-related dyspnea a trial of inhaled bronchodilator therapy is justified; for those with a propensity for recurrent infective exacerbations, consideration of additional anti-inflammatory treatment seems reasonable. In this paper, we review the current knowledge base and emerging paradigm for the pharmacological treatment of mild to moderate COPD.     

Essential role of hypothalamic muscarinic and alpha-adrenergic receptors in atrial natriuretic peptide release induced by blood volume expansion.

Expansion of the blood volume induces natriuresis, which tends to return the blood volume to normal. This response is mediated at least in part by the release of atrial natriuretic peptide (ANP) into the circulation. Previous experiments have shown the participation of the anterior ventral third ventricular (AV3V) region of the hypothalamus in the ANP release that follows volume expansion. When injected into the AV3V region, the cholinergic drug carbachol induces natriuresis and the release of ANP. In the present experiments, microinjection of norepinephrine into the AV3V region induced natriuresis and an increase in plasma ANP. To determine whether cholinergic and alpha-adrenergic pathways are crucial to the volume expansion-induced release of ANP, certain receptor-blocking drugs were injected into the AV3V region of conscious rats. Thirty minutes later blood volume was expanded by intravenous injection of 2.0 ml/100 g of body weight of hypertonic saline (0.3 M NaCl). Microinjection of isotonic saline (2 microliters) into AV3V region of control animals 30 min prior to volume expansion had no effect on the 3-fold increase in plasma ANP concentrations measured 5 min after volume expansion. In contrast, although the receptor-blocking drugs did not alter the initial concentrations of plasma ANP 30 min later, just prior to volume expansion, blockade of muscarinic cholinergic receptors by intraventricular injection of 5 nmol (2 microliters) of atropine sulfate or methylatropine markedly reduced the response to volume expansion but did not obliterate it. Microinjection of the alpha receptor blocker phentolamine (5 nmol) into the AV3V 30 min prior to volume expansion also markedly suppressed the ANP response. Intraperitoneal (i.p.) injection of methylatropine (0.01 mmol/100 g of body weight), which does not cross the blood-brain barrier, also did not affect the basal levels of ANP 30 min after i.p. injection. But, in striking contrast with the blockade of the response to volume expansion induced by intraventricular injection of methylatropine, the response to volume expansion was markedly enhanced by i.p. injection of methylatropine. The results therefore indicate that hypothalamic muscarinic and alpha-adrenergic synapses are essential to release of ANP in response to volume expansion. These results are consistent with a hypothetical pathway for physiological control of ANP release which involves distension of baroreceptors within the right atria, carotid and aortic sinuses, and kidney which alters afferent input to brain stem noradrenergic neurons with axons projecting to the AV3V region. There they activate cholinergic interneurons by an alpha 1-adrenergic synapse. The cholinergic neurons in turn stimulate ANP neurons in this brain region via muscarinic receptors. The stimulation of these neurons activates efferent pathways which induce the release of ANP.     

Irreversible erythrocyte volume expansion induced by tellurite

Tellurite (K2TeO3) has been suggested as a potential anti-sickling compound because it causes a selective increase in the water content of RBC. To investigate the conditions underlying the increase in RBC volume due to tellurite, normal RBCs were incubated with the compound in a physiological medium and the cells washed with a 10-fold volume of the medium. The washed cells were then incubated at 24 degrees C for periods up to 4 h and the following parameters were determined: MCV, MCH, MCHC and supernatant haemoglobin concentration by standard methods, the density distribution profile by phthalate esters and cell morphology by scanning electron microscopy (SEM). The effect of hypertonic PBS on the tellurite-treated cells was also tested. K2TeO3 induced concentration and time dependent increases in MCV and decreases in MCHC without any apparent change in MCH. The median density and the transitional 60% density range of the cell distribution profile respectively decreased and increased in proportion to [K2TeO3] and time. Hypertonic PBS did not inhibit or reverse the tellurite-induced changes in MCV and MCHC. SEM and photovolumetric measurements demonstrated tellurite-induced large vesicles ranging in size from 24 to 32 micron 3. The proportion of these vesicles increased with time and K2TeO3 concentration. Since tellurite is an oxidant, these findings suggest that its influx into the red cell results in irreversible reactions that disrupt the ion and water regulatory properties of the membrane.     

Hemodynamic and humoral effects of intravenous dilevalol in patients with moderate hypertension

The acute hemodynamic and humoral responses to intravenous dilevalol (10 to 390 mg) were evaluated in 10 patients with moderate hypertension. Dilevalol, in doses of 30 mg or more, decreased arterial pressure (p less than 0.0001) through a decrease in total peripheral resistance (p less than 0.0001) associated with an increase in stroke volume and cardiac output (p less than 0.0001). Heart rate increased moderately at doses above 190 mg. Plasma norepinephrine levels increased (p less than 0.05), but epinephrine levels remained unchanged. Plasma renin activity and level of atrial natriuretic peptide decreased (p less than 0.01 and p less than 0.01, respectively). The hypotensive and humoral changes persisted 3 hours after the last dose. Dilevalol modified the pattern of hemodynamic response to isometric stress, slightly enhancing the increases in peripheral resistance and blunting increases in cardiac output and heart rate. The response in arterial pressure during administration of dilevalol remained similar to that seen in the pretreatment phase. The results show that dilevalol, when given intravenously in a dose of 30 to 90 mg, reduces arterial pressure by reducing total peripheral resistance without acceleration in heart rate. On the basis of these hemodynamic effects, dilevalol should be further evaluated for treatment of hypertensive emergencies.     

Renal response to acute volume expansion in primary hyperaldosteronism

The exaggerated natriuretic response to extracellular fluid volume expansion (VE) observed in essential hypertension (EH) is related directly to blood pressure (BP) and indirectly to plasma renin activity (PRA). In order to evaluate the precise role of different hormonal parameters, the response to acute VE (isotonic saline, 1,800 ml IV over 3 hours) was assessed in 14 patients with primary aldosteronism (PA, surgically proven adrenal adenoma) and 18 clinically matched EH. At the time of the maneuver, BP and sodium intake were similar in the two groups, but serum potassium (2.89 +/- 0.13 vs 3.69 +/- 0.09 mmol/l), PRA (0.9 +/- 0.2 vs 3.5 +/- 0.9 ng/ml/h) and plasma aldosterone concentration (PAC, 25.9 +/- 3.8 vs 12.6 +/- 1.6 ng/dl) were significantly different. During VE, sodium excretion (UNaV) increased more in PA than in EH (98.1 +/- 15.2 vs 63.5 +/- 7.9 mmol/3 h); moreover, the slope of the regression line relating UNAVVE to UNaVcontrol was significantly steeper in PA. By contrast, the change in BP and indices of VE (hematocrit and plasma protein concentration) as well as the decrease in PRA (-45 +/- 9 vs -43 +/- 5 p. 100) and the increase in ANP (+ 65 +/- 16 vs + 69 +/- 28 p. 100) were similar in the two groups. VE left PAC unchanged in PA, whilst it decreased PAC in EH. We conclude that the natriuretic response to volume expansion is more marked in primary aldosteronism than in essential hypertension, a difference which is not explained by variations in the renin-angiotensin system or atrial natriuretic peptide.     

静脉应用速尿的不同方式对充血性心力衰竭疗效的影响

目的：观察静脉泵人与静脉注射速尿治疗中重度充血性心力衰竭（CHF）的临床效果。方法：86例CHF患者被随机分为静脉泵入组与静脉注射组,各43例。两组均给予心衰的基础治疗,静脉泵入组速尿100mg／d,20mg／h持续静脉泵人5h．静脉注射组100mg／d,1次静注。共观察7d,治疗前后测体重、左室射血分数（LVEF）、心输出量（CO）、6min步行距离。结果：静脉泵入组总有效率为88．4％,静脉注射组的79．1％,差异有显著性（P〈0．05）。静脉泵入组体重、LVEF、CO、6min步行距离改善明显优于静脉注射组（P〈0．05）。结论：静脉泵人速尿治疗CHF的疗效优于静脉注射。     

Adaptive responses to sustained volume expansion in hyponatraemic rats

Studies were carried out to evaluate adaptive responses to water retention in an experimental model of the syndrome of inappropriate antidiuresis (SIAD). Hyponatraemia was induced by continuous s.c. infusions of the antidiuretic vasopressin analogue 1-deamino-[8-D-arginine]-vasopressin in rats ingesting a 5% (w/v) dextrose solution. After 48 h of sustained decreases in the plasma concentration of Na+ to 23-25% of normal levels, all body fluid compartments were significantly expanded: plasma volume estimated by changes in plasma protein concentration was increased by 26%, extracellular fluid volume estimated by 22Na volume of distribution was increased by 24%, and total body water estimated by 3H2O volume of distribution was increased by 16%. Despite marked increases in all body fluid compartment volumes, mean arterial blood pressure was only modestly increased to 110 +/- 2 mmHg in conscious hyponatraemic rats. Consistent with the sustained volume expansion, both basal and stimulated plasma renin activities were significantly suppressed in the hyponatraemic rats. Plasma vasopressin levels were similarly suppressed, and the hyponatraemic rats showed a striking absence of endogenous vasopressin secretion in response to marked intravascular volume depletion (15-45%) produced by s.c. administration of polyethylene glycol. Plasma concentrations of atrial natriuretic peptide were initially stimulated four- to fivefold above basal levels in response to the water-induced volume expansion, but by 48 h fell to ranges not significantly different from basal unstimulated levels, despite continued plasma and extracellular fluid volume expansion at that time. These results illustrate that multiple haemodynamic and hormonal adaptive responses occur with sustained dilutional hyponatraemia in rats, and suggests that these can be of sufficient magnitude to allow continued water retention without necessarily provoking either escape from antidiuresis or continued natriuresis. In contrast with previous studies in experimental animals in which hyponatraemia was maintained by continuous forced administration of hypotonic fluid, rats in this model reached a steady state with characteristics resembling many of those observed clinically in patients with SIAD.