Crystallisation in basaltic magmas revealed via in situ 4D synchrotron X-ray microtomography.

Magma crystallisation is a fundamental process driving eruptions and controlling the style of volcanic activity. Crystal nucleation delay, heterogeneous and homogeneous nucleation and crystal growth are all time-dependent processes, however, there is a paucity of real-time experimental data on crystal nucleation and growth kinetics, particularly at the beginning of crystallisation when conditions are far from equilibrium. Here, we reveal the first in situ 3D time-dependent observations of crystal nucleation and growth kinetics in a natural magma, reproducing the crystallisation occurring in real-time during a lava flow, by combining a bespoke high-temperature environmental cell with fast synchrotron X-ray microtomography. We find that both crystal nucleation and growth occur in pulses, with the first crystallisation wave producing a relatively low volume fraction of crystals and hence negligible influence on magma viscosity. This result explains why some lava flows cover kilometres in a few hours from eruption inception, highlighting the hazard posed by fast-moving lava flows. We use our observations to quantify disequilibrium crystallisation in basaltic magmas using an empirical model. Our results demonstrate the potential of in situ 3D time-dependent experiments and have fundamental implications for the rheological evolution of basaltic lava flows, aiding flow modelling, eruption forecasting and hazard management.

CO2 flux from Javanese mud volcanism.

Studying the quantity and origin of CO2 emitted by back-arc mud volcanoes is critical to correctly model fluid-dynamical, thermodynamical, and geochemical processes that drive their activity and to constrain their role in the global geochemical carbon cycle. We measured CO2 fluxes of the Bledug Kuwu mud volcano on the Kendeng Fold and thrust belt in the back arc of Central Java, Indonesia, using scanning remote sensing absorption spectroscopy. The data show that the expelled gas is rich in CO2 with a volume fraction of at least 16 vol %. A lower limit CO2 flux of 1.4 kg s-1 (117 t d-1) was determined, in line with the CO2 flux from the Javanese mud volcano LUSI. Extrapolating these results to mud volcanism from the whole of Java suggests an order of magnitude total CO2 flux of 3 kt d-1, comparable with the expected back-arc efflux of magmatic CO2. After discussing geochemical, geological, and geophysical evidence we conclude that the source of CO2 observed at Bledug Kuwu is likely a mixture of thermogenic, biogenic, and magmatic CO2, with faulting controlling potential pathways for magmatic fluids. This study further demonstrates the merit of man-portable active remote sensing instruments for probing natural gas releases, enabling bottom-up quantification of CO2 fluxes.

Role of syn-eruptive plagioclase disequilibrium crystallization in basaltic magma ascent dynamics.

Timescales of magma ascent in conduit models are typically assumed to be much longer than crystallization and gas exsolution for basaltic eruptions. However, it is now recognized that basaltic magmas may rise fast enough for disequilibrium processes to play a key role on the ascent dynamics. The quantification of the characteristic times for crystallization and exsolution processes are fundamental to our understanding of such disequilibria and ascent dynamics. Here we use observations from Mount Etna's 2001 eruption and a magma ascent model to constrain timescales for crystallization and exsolution processes. Our results show that plagioclase reaches equilibrium in 1-2 h, whereas ascent times were <1 h. Using these new constraints on disequilibrium plagioclase crystallization we also reproduce observed crystal abundances for different basaltic eruptions. The strong relation between magma ascent rate and disequilibrium crystallization and exsolution plays a key role in controlling eruption dynamics in basaltic volcanism.

Influence of indomethacin on the natriuretic and renin-stimulating effect of bumetanide in essential hypertension.

The effect of bumetanide on absolute and fractional sodium excretion, creatinine clearance, and plasma renin activity (PRA) was studied in eight patients with essential hypertension before and after indomethacin. After bumetanide, urinary sodium excretion increased only in the first 4 hr, creatinine clearance only in the first 2 hr, and PRA rose progressively. After indomethacin, bumetanide caused a smaller increase in urinary sodium excretion, decreased creatinine clearance, and caused a small early and late PRA rise. Prostaglandin inhibition and indomethacin did not, per se, affect the tubular natriuretic mechanism but they abolished both early vascular and sustained PRA-stimulating effects of bumetanide.

Lack of effect of percutaneous transluminal renal angioplasty on nocturnal hypotension in renovascular hypertensive patients.

OBJECTIVE: To investigate whether nocturnal blood pressure fall is blunted in renovascular hypertension and can therefore be used as a diagnostic criterion for this condition. METHODS: In 14 renovascular hypertensive patients (age 43.8+/-2.1 years, mean+/-SEM, clinic blood pressure 173.6+/-3.7 mmHg systolic and 109.0+/-2.0 mmHg diastolic) and in 14 age- and blood pressure-matched essential hypertensive controls 24 h ambulatory blood pressure was measured after washout from drug treatment, during angiotensin converting enzyme inhibitor treatment and, in renovascular hypertension, also after percutaneous transluminal renal angioplasty. RESULTS: The 24 h average systolic and diastolic blood pressures were 146.4+/-5.7 and 97.5+/-3.6 mmHg in renovascular and 144.3+/-1.2 and 98.0+/-2.2 mmHg in essential hypertensive patients. The angiotensin converting enzyme inhibitor treatment reduced 24 h average systolic and diastolic blood pressures by 8.5% and 9.7% in the renovascular and by 8.3% and 10.8% in the essential hypertensive group. Greater systolic and diastolic blood pressure reductions (-18.2% and -18.1%) were observed in renovascular hypertensive patients after percutaneous transluminal renal angioplasty. Blood pressure fell by about 10% during the night and the fall was similar in renovascular and in essential hypertensive patients. In the former group, nocturnal hypotension was similar after washout, during angiotensin converting enzyme inhibitor treatment and after percutaneous transluminal renal angioplasty. Similar results were obtained for nocturnal bradycardia. CONCLUSIONS: Nocturnal blood pressure fall is equally manifest in renovascular and essential hypertension. The removal of the renal artery stenosis and blood pressure normalization do not enhance this phenomenon. Nocturnal hypotension seems therefore to be unaffected by renovascular hypertension.

Chronic dose-response curve of enalapril in essential hypertensives. An Italian multicenter study.

We have previously shown that enalapril, when given acutely to renovascular patients, exerted a dose-dependent hypotensive effect. To address the same problem in chronically treated essential hypertensives, we studied 116 uncomplicated essential hypertensives, whose diastolic blood pressure was greater than or equal to 95 mm Hg at the end of a two-week placebo run-in period (time 0). According to a randomized crossover design, these patients received three doses (10, 20, or 40 mg) of enalapril qd and a placebo, each treatment being given for one month. At the end of each treatment period as well as at time 0, blood pressure and heart rate were measured 24 hours after the last dosing. In spite of a two-week run-in placebo period, placebo treatment further and significantly reduced blood pressure; however enalapril further and significantly reduced blood pressure when compared to placebo. Although absolute blood pressure values after 40 mg of enalapril were significantly lower than those after 10 mg of enalapril the relevance of this difference, mainly when compared to placebo, seems to be inconsistent. Taken together these data suggest that the hypotensive effect of enalapril chronically given to essential hypertensives and measured 24 hours after last dosing, is dose independent.

Acute hemodynamic (systemic and renal) and humoral effects of three increasing doses of iloprost in essential hypertensives.

To evaluate the acute hemodynamic, both systemic and renal, and humoral effect of three increasing doses of Iloprost, a prostacyclin analogue, eight uncomplicated untreated hospitalized patients with mild to moderate essential hypertension, while on a constant sodium and potassium intake, received, after oral hydration, three doses of Iloprost (1,2 or 4 ng/kg/body weight for 45 min) in a single-blind randomized sequence. Each dose was preceded by placebo (saline infusion for 45 min) with a 48 h interval between each study. Iloprost significantly (P less than .05) reduced blood pressure, and increased heart rate, filtered sodium, urinary sodium excretion, fractional sodium excretion, noradrenaline, adrenaline, and plasma renin activity (PRA). The blood pressure lowering effect as well as the heart rate, renal plasma flow and noradrenaline increases were significantly greater on the 4 ng dose. Glomerular filtration rate and adrenaline showed a dose-dependent increase; urinary sodium excretion and fractional sodium excretion were similarly increased by the three doses. No correlation was found between urinary sodium excretion and either glomerular filtration rate or renal plasma flow. The data obtained indicate that Iloprost causes reduction of blood pressure with a reflex activation in the sympathetic nervous system and stimulation of renin secretion, renal vasodilation mainly at the level of the afferent arteriole, and natriuresis. This latter effect is probably due to a direct inhibition of tubular reabsorption, which, at variance with the other effects, is dose-independent.

Dipyridamole decreases circulating renin-angiotensin system activity in hypertensive patients.

To study the effect of adenosine on renin release, n = 6 hypertensive patients, while on a constant 80 to 100 mEq/24 h Na+ diet, received oral 150 mg dipyridamole (an adenosine uptake inhibitor) three times daily for 3 days while upright plasma renin activity (PRA) and plasma aldosterone, urinary aldosterone, plasma and urinary Na+,K+, and creatinine clearance were monitored the day before (basal) the first and third day of the treatment and the day after the withdrawal (recovery). As compared to basal and to recovery, dipyridamole significantly decreased PRA, and plasma and urinary aldosterone without affecting plasma and urinary Na+ and K+, creatinine clearance, blood pressure, and heart rate. These data, showing that dipyridamole decreases PRA and aldosterone, confirm also in hypertensives that endogenous adenosine inhibits the circulating renin-angiotensin-aldosterone system.

Acute dose-response curve of enalapril in renovascular hypertensives.

We evaluated the acute blood pressure lowering effect of enalapril in terms of dose-response curve and compared this effect with that on humoral parameters. Eleven renovascular patients with acute angiotensin-converting enzyme (ACE) inhibition received (according to a randomized double-blind cross-over design) placebo, 10, 20, and 40 mg of enalapril with a 72-hour interval between each dose. Seated blood pressure and heart rate were measured every hour for 6 hours and then again at the twelfth and twenty-fourth hour, while venous blood samples for plasma renin activity, plasma aldosterone and serum ACE measurements were obtained at the fourth and twenty-fourth hour after receiving the placebo or drug. Blood pressure was significantly reduced by all three doses of enalapril at hour 4, while at hour 24 it was reduced only by the 20- and 40-mg doses. A significant correlation (r = 0.68; P less than 0.001) was found between percentage decrements of mean blood pressure and the log of the doses at hour 4 with a similar (although not significant) trend at hour 24. Plasma renin activity was significantly and to a similar extent increased by the three doses of enalapril at hour 4, while at hour 24 it was significantly increased only by the 40-mg dose. Serum ACE and plasma aldosterone were significantly reduced both at hours 4 and 24 without any difference between doses. No correlation was found between mean blood pressure changes and those of humoral factors.(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment of renovascular disease and of renovascular hypertension.

Treatment of occlusive lesions of renal arteries, defined as renovascular disease (RVD), is aimed both at preventing ischemic renal disease (IRD) and rescuing renal function through revascularization procedures, such as PTRA, endovascular stenting and surgical revascularization, as well as curing or improving hypertension in the presence of renovascular hypertension (RVH), i.e. hypertension caused by these vascular lesions. Preventive treatment of IRD is still an individual decision making process based on the type of renal lesions, degree of renal stenosis and progressive loss of renal mass as well as on immediate and late technical success of revascularization procedures together with their rate of complications. Rescue of renal function and-or prediction of the outcome of renal function after successful revascularization depends not only on the possibility of clarifying whether the decrease in renal function is a functioning-reversible phenomenon linked to renal hypoperfusion but also on the potential risk that the revascularization procedure may induce irreversible kidney damage. The rationale for treating RVH through revascularization procedures derives from the possibility of establishing a pathogenetic link between the occlusive lesions and hypertension, mainly through renal vein renin measurement and captopril renography and possibly their combination. Finally, medical treatment of hypertension is needed in patients who cannot undergo or refuse revascularization and whose blood pressure is not normalized by these procedures.

Angiotensin-converting enzyme inhibitors in hypertension: a review.

Angiotensin-converting enzyme (ACE) inhibitors are a new class of drugs, whose main indications are the treatment of hypertension and of heart failure. Data obtained with captopril, the first orally active ACE inhibitor, affords an understanding of the rationale of their therapeutic use based on the knowledge of their mechanisms of action, efficacy, contraindications and precautions, dosage and frequency of administration, side-effects, interactions and advantages. ACE inhibitors appear to exert their haemodynamic effect mainly by inhibiting the renin-angiotensin-aldosterone system, but also by modulating sympathetic nervous system activity and by increasing prostaglandin synthesis. Therefore they act both on vasoconstrictor and volume factors, since they cause vasodilation (the main effect) and mild natriuresis without affecting the heart rate and contractility and, probably, favourably influencing renal, coronary and cerebral circulation. So far it appears that ACE inhibitors can be usefully employed in the treatment of heart failure, in which they reduce both pre- and after-load, and mainly of hypertension. In the past captopril has been used to treat only severe and or resistant hypertension and some secondary forms, like renal parenchymal and renovascular hypertension, but now it seems that captopril is useful also to treat mild to moderate essential hypertension. Their efficacy in reducing blood pressure is similar to that of thiazide diuretics and of beta-blockers, the two drugs now considered of first choice and they exert their hypotensive action without the development of pseudotolerance or tolerance. ACE inhibitors seem, at the moment, contraindicated in pregnancy and in hyperkalaemic syndromes and must be used with caution in patients with collagen disease (mainly associated with renal failure), with severe bilateral renal artery stenosis (and with severe artery stenosis of a solitary kidney) and with severe sodium depletion. It is now established that captopril has a flat dose response curve and that it must be given (twice daily) at a dose not exceeding 150 mg/day. The same pharmacological approach must be used with future ACE inhibitors in order to establish the right posology and the frequency of administration. In this respect enalapril seems to be a promising ACE inhibitor with a prolonged action (at least 24 hours). The exact posology of ACE inhibitors might be crucial, since it has been shown that the side-effects of captopril (skin rashes, fever, taste disturbances, proteinuria and neutropenia) are dose dependent.(ABSTRACT TRUNCATED AT 400 WORDS)

[Renin and aldosterone]. / Renina e aldosterone

The radioimmunological dosages of renin and of aldosterone are used nowadays in clinical practice for research purposes only. The measurement of activity of plasma renin may be considered a significant indication of the concentration of the enzime in plasma and, indirectly, of its secretion. Several factors take a part in the regulation of renin secretion (mean arterial pressure, introduction of sodium and potassium, the sympathetic nervous system, ADH and concentration of angiotensin II in plasma). In pathological conditions such factors may cause alteration of the renin-angiotensin II system, thus determining hyperreninisms and hyporeninisms, whether associated with arterial hypertension or not. Several factors take a part on aldosterone secretion too (ACTH, sodiaemia, potassiaemia, renin-angiotensin II system). In pathological conditions the alteration of the regulation system may lead to hyperaldosteronism or to hypoaldosteronism of primary or secondary type. A survey of recent research on the physiopathology of the renin-aldosterone system is also given.

Trough:peak ratio of the blood pressure response to angiotensin converting enzyme inhibitors.

SHORT- VERSUS LONG-ACTING ANGIOTENSIN CONVERTING ENZYME (ACE) INHIBITORS: Although ACE inhibitors are widely used in the treatment of hypertension, there are few data on trough:peak ratios and the data are contradictory. Part of the explanation for this lies in differences in pharmacological properties. Depending on the kinetics of elimination, the trough:peak ratio of short- and long-acting ACE inhibitors has to be evaluated according to a dose regimen of twice or once a day, respectively, and must take account of the dose used, since long-acting ACE inhibitors appear to have a dose-dependent trough:peak effect. Further explanations for the contradictory trough:peak ratios reported for ACE inhibitors include measurement methods (clinic blood pressure versus ambulatory monitoring) and study design. TROUGH:PEAK RATIO: Data from randomly allocated, placebo-controlled studies indicate that both the short-acting ACE inhibitors captopril and quinapril given twice a day and the long-acting ACE inhibitors enalapril, lisinopril, benazepril and cilazapril given once a day have an acceptable trough:peak ratio (> 50%). The evidence suggests that when chemically different ACE inhibitors with similar kinetics of elimination are administered at equipotent doses, similar trough:peak ratios are obtained.

Potassium-rich and sodium-poor salt reduces blood pressure in hospitalized patients.

To investigate whether a K-rich/Na-poor salt is able to reduce blood pressure, 10 mildly hypertensive inpatients (six males) aged 28-53 years, with supine diastolic blood pressure (DBP) greater than 95 mmHg after 5 days of hospitalization, on a standard diet containing about 20 mmol Na plus 4 g common salt (CS) were randomly given, in double-blind conditions, 2 g twice daily of either CS (five patients) or K-rich/Na-poor salt (five patients) to add to food for a further 8 days. Mean blood pressure was significantly (P less than 0.01) reduced to a similar extent in both groups in the first 4 days, and declined significantly (P less than 0.01) only in the K/Na group in the following 8 days, reaching values significantly (P less than 0.01) lower than those of the CS group. The heart rate did not change significantly while body weight decreased to a similar extent in both groups. Urinary sodium excretion was similarly and significantly (P less than 0.01) reduced in both groups in the first 4 days (CS 100.8 +/- 7.9 and K/Na 100.2 +/- 11.0 mmol/24 h, and remained unchanged in the CS group (109.9 +/- 4.3 mmol/24 h) but declined significantly (P less than 0.05) by about 50% in the K/Na group (62.9 +/- 3.6 mmol/24 h) in the following 8 days. Plasma renin activity (PRA) and plasma noradrenaline did not differ significantly between the two groups, nor among the days of treatment, but the mean blood pressure response to mental stress was reduced significantly (P less than 0.4) in the Na/K group compared with the CS group.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of increasing doses of labetalol on blood pressure, plasma renin activity and aldosterone in hypertensive patients.

1. Four different doses of labetalol (150, 300, 600 and 900 mg/day) were given for 1 week to each of four groups of patients with essential hypertension (six patients for each group). 2. Labetalol decreased mean blood pressure and heart rate to the same extent on the first and the seventh days of treatment. Only standing blood pressure showed a dose-dependent inhibition both in the supine and upright position. 3. Labetalol exerted a net inhibitory effect on plasma renin activity, which was related to basal renin values and was already maximal at the lowest doses. This effect was well maintained in the supine position. This effect was well maintained in the supine position, although during standing it tended to be less evident with increasing doses. 4. Urinary aldosterone was decreased in a dose-dependent fashion and its changes were largely independent fashion and its changes were largely independent of plasma renin activity. 5. Neither basal values nor changes of renin and aldosterone were related to the hypotensive effect of labetalol. 6. During labetalol treatment urinary sodium excretion fell for 2-3 days and then returned to basal values. The retentive effect of labetalol on sodium was directly related to the decrease of blood pressure, and the successive sodium escape might be explained either by the observed increase of plasma volume (indirectly measured by packed cell volume) or by aldosterone inhibition.

What effect does blood pressure control have on the progression toward renal failure?

Since hypertension is associated with nephrosclerosis and an increased progression toward end-stage renal failure, the therapeutic approach to the treatment of hypertension should aim to protect the kidney against damage or to halt the progression toward end-stage renal failure. It appears that compared with systolic and mean blood pressure, the level of diastolic blood pressure is particularly associated with renal damage. In the presence of kidney failure the choice of antihypertensive drug should be made according to pharmacokinetic and pharmacodynamic properties. From the pharmacokinetic point of view, drugs that are eliminated via the biliary route are preferable since no dosage adjustment is required, and those with a favorable trough to peak effect can achieve better blood pressure control by reducing blood pressure variability. Pharmacodynamic properties should include efficacy in lowering blood pressure, beneficial renal effects, and good tolerability. Hence, the dihydropyridine calcium antagonists, which are effective during volume repletion and which counteract vasoconstrictor mechanisms, seem to be particularly effective. There is some suggestion, but no definitive proof, that blood pressure should be lowered well below 140/90 mm Hg; to achieve this, combination therapy frequently must be used. The rationale for combining two or more antihypertensive drugs is based on the knowledge that this combination can exert an additive antihypertensive action while reducing side effects. The combination of an angiotensin converting enzyme inhibitor with a dihydropyridine calcium antagonist may well fulfill these criteria since this combination could enhance both antihypertensive and renal hemodynamic effects in comparison to single-drug treatment and could reduce the side effects of both drugs.

Endothelium-dependent forearm vasodilation is reduced in normotensive subjects with familial history of hypertension.

Endothelium-dependent vasodilation is reduced in essential hypertensive subjects. To evaluate whether this abnormality is a primary defect or is a consequence of blood pressure increment, in offspring of essential hypertensive and normotensive subjects (n = 13 subjects for each group) matched for age, sex, body weight, and blood pressure, we studied the response of forearm vasculature to acetylcholine (ACh) (an endothelium-dependent vasodilator), sodium nitroprusside (a direct vasodilator of vascular smooth muscle), and forearm ischemia (13 min plus 1 min of exercise) to induce maximal vasodilation. Drugs were infused into the brachial artery at cumulative doses (ACh: 0.15, 0.45, 1.5, 4.5, and 15 micrograms/100 ml of forearm tissue/min; sodium nitroprusside: 1, 3, and 10 micrograms/100 ml of forearm tissue/min) while forearm blood flow was measured by strain-gauge venous plethysmography. The intra-arterial blood pressure and heart rate were continuously monitored. Despite a comparable forearm vascular response to sodium nitroprusside and to forearm ischemia, the effect of ACh was significantly (p < 0.001) reduced in offspring of hypertensive subjects compared to the offspring of normotensive subjects. These data indicate that ACh-mediated forearm vasodilation is reduced in normotensive subjects with a familial history of essential hypertension, a finding that suggests that endothelium dysfunction can precede the appearance of hypertension and that this abnormality might play a role in the pathogenesis of essential hypertension.