Differential effects of captopril and nitrates on muscle sympathetic nerve activity in volunteers

BACKGROUND The sympathetic nervous system (SNS) is an important regulator of cardiovascular function. Activation of SNS plays an important role in the pathophysiology and the prognosis of cardiovascular diseases such as heart failure, acute coronary syndromes, arrhythmia, and possibly hypertension. Vasodilators such as adenosine and sodium nitroprusside are known to activate SNS via baroreflex mechanisms. Because vasodilators are widely used in the treatment of patients with cardiovascular diseases, the aim of the present study was to assess the influence of clinically used dosages of isosorbide dinitrate and captopril on sympathetic nerve activity at rest and during stimulatory maneuvers. METHODS AND RESULTS Twenty-eight healthy volunteers were included in this double-blind placebo-controlled study, and muscle sympathetic nerve activity (MSA; with microelectrodes in the peroneal nerve), blood pressure, heart rate, and neurohumoral parameters were measured before and 90 minutes after the oral administration of 40 mg isosorbide dinitrate or 6.25 mg captopril. Furthermore, a 3-minute mental stress test and a cold pressor test were performed before and 90 minutes after drug administration. Resting MSA did not change after captopril and decreased compared with placebo (P < .05 versus placebo), whereas isosorbide dinitrate led to a marked increase in MSA (P < .05). Systolic blood pressure was reduced by isosorbide dinitrate (P < .05), whereas captopril decreased diastolic blood pressure (P < .05). The increases in MSA, blood pressure, and heart rate during mental stress were comparable before and after drug administration regardless of the medication. During cold pressor test, MSA and systolic and diastolic blood pressures increased to the same degree independent of treatment, but after isosorbide dinitrate, the increase in MSA seemed to be less pronounced. Heart rate did not change during cold stimulation. Plasma renin activity increased after captopril and isosorbide dinitrate (P < .05), whereas placebo had no effect. Endothelin-1 increased after placebo and isosorbide dinitrate (P < .05) but not after captopril. CONCLUSIONS Thus, captopril suppressed MSA despite lowering of diastolic blood pressure but allowed normal adaptation of the SNS during mental or physical stress. In contrast, the nitrate strongly activated the SNS under baseline conditions. These findings demonstrate that vasodilators differentially interact with the SNS, which could be of importance in therapeutic strategies for the treatment of patients with cardiovascular diseases.

Dating groundwater in the Bohemian Cretaceous Basin: Understanding tracer variations in the subsurface

The northern section of the Bohemian Cretaceous Basin has been the site of intensive U exploitation with harmful impacts on groundwater quality. The understanding of groundwater flow and age distribution is crucial for the prediction of the future dispersion and impact of the contamination. State of the art tracer methods (3H, 3He, 4He, 85Kr, 39Ar and 14C) were, therefore, used to obtain insights to ageing and mixing processes of groundwater along a north–south flow line in the centre of the two most important aquifers of Cenomanian and middle Turonian age. Dating of groundwater is particularly complex in this area as: (i) groundwater in the Cenomanian aquifer is locally affected by fluxes of geogenic and biogenic gases (e.g. CO2, CH4, He) and by fossil brines in basement rocks rich in Cl and SO4; (ii) a thick unsaturated zone overlays the Turonian aquifer; (iii) a periglacial climate and permafrost conditions prevailed during the Last Glacial Maximum (LGM), and iv) the wells are mostly screened over large depth intervals. Large disagreements in 85Kr and 3H/3He ages indicate that processes other than ageing have affected the tracer data in the Turonian aquifer. Mixing with older waters (>50 a) was confirmed by 39Ar activities. An inverse modelling approach, which included time lags for tracer transport throughout the unsaturated zone and degassing of 3He, was used to estimate the age of groundwater. Best fits between model and field results were obtained for mean residence times varying from modern up to a few hundred years. The presence of modern water in this aquifer is correlated with the occurrence of elevated pollution (e.g. nitrates). An increase of reactive geochemical indicators (e.g. Na) and radiogenic 4He, and a decrease in 14C along the flow direction confirmed groundwater ageing in the deeper confined Cenomanian aquifer. Radiocarbon ages varied from a few hundred years to more than 20 ka. Initial 14C activity for radiocarbon dating was calibrated by means of 39Ar measurements. The 14C age of a sample recharged during the LGM was further confirmed by depleted stable isotope signatures and near freezing point noble gas temperature. Radiogenic 4He accumulated in groundwater with concentrations increasing linearly with 14C ages. This enabled the use of 4He to validate the dating range of 14C and extend it to other parts of this aquifer. In the proximity of faults, 39Ar in excess of modern concentrations and 14C dead CO2 sources, elevated 3He/4He ratios and volcanic activity in Oligocene to Quaternary demonstrate the influence of gas of deeper origin and impeded the application of 4He, 39Ar and 14C for groundwater dating.

Placing unprecedented recent fir growth in a European-wide and Holocene-long context

Forest decline played a pivotal role in motivating Europe's political focus on sustainability around 35 years ago. Silver fir (Abies alba) exhibited a particularly severe dieback in the mid-1970s, but disentangling biotic from abiotic drivers remained challenging because both spatial and temporal data were lacking. Here, we analyze 14 136 samples from living trees and historical timbers, together with 356 pollen records, to evaluate recent fir growth from a continent-wide and Holocene-long perspective. Land use and climate change influenced forest growth over the past millennium, whereas anthropogenic emissions of acidic sulfates and nitrates became important after about 1850. Pollution control since the 1980s, together with a warmer but not drier climate, has facilitated an unprecedented surge in productivity across Central European fir stands. Restricted fir distribution prior to the Mesolithic and again in the Modern Era, separated by a peak in abundance during the Bronze Age, is indicative of the long-term interplay of changing temperatures, shifts in the hydrological cycle, and human impacts that have shaped forest structure and productivity.