Acute Lead Exposure Increases Arterial Pressure: Role of the Renin-Angiotensin System

Background: Chronic lead exposure causes hypertension and cardiovascular disease. Our purpose was to evaluate the effects of acute exposure to lead on arterial pressure and elucidate the early mechanisms involved in the development of lead-induced hypertension. Methodology/Principal Findings: Wistar rats were treated with lead acetate (i.v. bolus dose of 320 μg/Kg), and systolic arterial pressure, diastolic arterial pressure and heart rate were measured during 120 min. An increase in arterial pressure was found, and potential roles of the renin-angiotensin system, Na+,K+-ATPase and the autonomic reflexes in this change in the increase of arterial pressure found were evaluated. In anesthetized rats, lead exposure: 1) produced blood lead levels of 37±1.7 μg/dL, which is below the reference blood concentration (60 μg/dL); 2) increased systolic arterial pressure (Ct: 109±3 mmHg vs Pb: 120±4 mmHg); 3) increased ACE activity (27% compared to Ct) and Na+,K+-ATPase activity (125% compared to Ct); and 4) did not change the protein expression of the α1-subunit of Na+,K+-ATPase, AT1 and AT2. Pre-treatment with an AT1 receptor blocker (losartan, 10 mg/Kg) or an ACE inhibitor (enalapril, 5 mg/Kg) blocked the lead-induced increase of arterial pressure. However, a ganglionic blockade (hexamethonium, 20 mg/Kg) did not prevent lead's hypertensive effect. Conclusion: Acute exposure to lead below the reference blood concentration increases systolic arterial pressure by increasing angiotensin II levels due to ACE activation. These findings offer further evidence that acute exposure to lead can trigger early mechanisms of hypertension development and might be an environmental risk factor for cardiovascular diseaseThis study was supported by grants from CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior) and CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico)/FAPES (Fundação de Amparo à Pesquisa do Espírito Santo)/FUNCITEC (Fundação de Ciência e Tecnologia)(39767531/07), Brazil and from MCINN (Ministerio de Ciencia e Innovación) (SAF 2009- 07201) and ISCIII (Instituto de Salud Carlos III) (Red RECAVA- Red Temática de Investigación en Enfermedades Cardiovasculares del Instituto de Salud Carlos III, RD06/0014/0011), Spai

Salt restriction in kidney disease—a missed therapeutic opportunity?

The importance of salt restriction in the treatment of patients with renal disease has remained highly controversial. In the following we marshal the current evidence that salt plays a definite role in the genesis of hypertension and target organ damage, point to practical problems of salt restriction, and report on novel pathomechanisms of how salt affects blood pressure and causes target organ damage

The Natriuretic Hormones

The title follows from the original demonstration by Dr. Hugh de Wardener in 1961 that a humoral agent is produced after extracellular volume expansion which results in a vigorous diuresis and natriuresis. Thus the name of "natriuretic hormone" was coined. In the years that followed several investigators pursued the search for the hormone. What resulted, however, was the discovery of several hormones with different characteristics, all of which were natriuretic. Initially it was found that the hormone was similar in action to ouabain or digoxin, hence the appelation of ouabain-like or digoxin-like. The hormone was found to be an inhibitor of Na-K-ATPase, which would fit with it being a cardiotonic steroid. On the other hand, neither ouabain or digoxin migrated on Sephadex gel filtration in the same locus as the hormone. Other investigators claim to have identified the hormone-initially as a vanadium-diascorbate, later as bufadienolides such as marinobufagenin, yet later as a macrocylic derivative of inorganic carbon suboxide with a molecular weight of 408 Da. Some support for the latter finding was derived from an earlier report that a semi-purified Sephadex-derived compound was found to have a molecular weight of about 12,000 Da but the active compound, when split from its carrier protein, had a molecular weight of exactly 408 Da. This compound had not been further identified. As further development was the demonstration by Bricker and colleagues that a natriuretic substance could be purified from uremic urine. This turned out to be a xathurenic acid derivative. Meanwhile the focus began to turn to natriuretic peptides derived from heart (ANF and BNP). These peptides have a shorter duration of action than the cardiotonic steroid-like hormone and ANF has proved to be most useful as a measure of heart failure. It should also be stressed that marinobufagenin, like ANF, is elevated in congestive heart failure, whereas the steroid-like hormone is depressed or absent in this state. This review will attempt to describe and contrast the properties of each of the proposed natriuretic hormones, including their locus on Sephadex separation, potency, duration of action, chemical structure (if known), behavior in hypertension, renal failure, heart failure, and brain disease. As most recent work has focussed on marinobufagenin, this hormone will be brought up to date by investigators in the field

Kartun Fisika

Judul Asli : The Cartoon Guide to Physicsvii, 212 p. : il.; 22 cm

Kartun fisika

Judul asli: The Cartoon guide of physicsvii, 212 p. : il.; 22 c

Kartun Fisika

vii, 212 halaman.; gambar, grafik.; 23 c