Renal adrenomedullin and high altitude diuresis.

Previous investigations revealed that most of the fluid regulating hormones showed no consistent relationship to the hypoxic diuretic response (HDR). In this study we examined if adrenomedullin (AM), a hypoxia-mediated diuretic/natriuretic peptide is connected to HDR. Thirty-three persons were examined at low altitude (LA), on the third exposure day at 3440 m (medium altitude, MA) and on the fourteenth day at 5050 m (high altitude, HA). Nocturnal diuresis rose from 460 ml [interquartile range 302 ml] at LA to 560 [660] ml at MA to 1015 [750] ml at HA (p<0.005). Sodium excretion was similar at LA and MA (41.8 [27.0] vs. 41.4 [28.4] mM) and increased to 80.2 [29.1] mM at HA (p<0.005). Urinary AM excretion was 7.9 [3.9] at LA, 7.5 [5.7] pM at MA, and increased to 10.5 [5.1] pM (p<0.05) at HA. Urinary AM excretion was correlated to diuresis (r=0.72, p<0.005) and sodium excretion (r=0.57, p<0.005). Plasma AM concentration rose from 16.4 [3.1] to 18.8 [4.9] pM/l at MA (p<0.005) and to 18.3 [4.3] pM/l at HA (p<0.005). Plasma AM concentration and urinary AM excretion were not correlated, neither were plasma AM concentration and diuresis or natriuresis. Our data suggest the involvement of increased renal AM production in the pathophysiology of high altitude fluid and sodium loss.

Chronic obstructive pulmonary disease and oxidative stress.

The respiratory tract as the main entrance for various inhalative substances has great potential to generate reactive species directly or indirectly in excess. Thus, heavy smokers are at high risk for development, impairment and failed response to treatment of chronic obstructive pulmonary disease (COPD). The article is an update regarding the influence of reactive oxygen (ROS) and nitrogen (RNS) species on COPD; however, we do not intend to describe ROS and RNS actions on the entire lung tissue. Here, we focus on the airways, because in human most of the described effects of ROS and RNS species are measured on respiratory epithelial cells obtained by bronchoscopy. ROS and RNS species are physiological compounds in cells and risk factors for several respiratory diseases. In general, both kinds of species are thermodynamically stabile, but their reaction behaviors in cellular environments are very different. For example, the life times of the superoxide anion radical range from micro/milliseconds up to minutes and even hours in in-vitro model systems. Oxidative stress by cigarette smoke was investigated in detail by the authors of this article. In addition, original studies by the authors on the amount of fine particulate matter and trace elements in lung biopsies after defined inhalation indicate a distortion of the equilibrium between oxidants and antioxidants. We also try to present some modern views with respect to genomic medicine for future therapeutic perspectives, although this is an upcoming sector of COPD therapy.

Orthostatic stimuli rapidly change plasma adrenomedullin in humans.

The aim of this study was to evaluate the effect of orthostasis on the time course of plasma adrenomedullin concentration. On 5 different days, normotensive subjects were randomized to undergo for 30 minutes either 12 degrees, 30 degrees, 53 degrees, or 70 degrees passive head-up tilt or to remain supine. Venous blood was collected from each subject in the supine position before tilting, at 3 and 27 minutes during tilting, and at 2 and 50 minutes after orthostasis. Plasma adrenomedullin increased significantly with tilt of >/=30 degrees in a stimulus-dependent manner. Approximately half of the increase seen at 27 minutes occurred during the first 2 minutes of upright positioning; the maximum effect with 70 degrees tilt was +70%. Elevations in norepinephrine, epinephrine, aldosterone, plasma renin activity, vasopressin, heart rate, and mean arterial pressure were also significant. Hematocrit, blood density, plasma density, and plasma volume loss rose (P<0.05) at 53 degrees and 70 degrees tilt. Our results indicate that adrenomedullin may play an important role in stabilization of hemodynamics during passive orthostasis. In conclusion, plasma adrenomedullin rapidly increases with orthostatic challenge in a stimulus-dependent manner and also swiftly returns to baseline levels after the subject resumes the supine position.

LBNP-induced changes in plasma cGMP with and without head down tilt bed rest.

This investigation was conducted to test the following hypotheses: 1) If simulated orthostasis (LBNP) reduces plasma cGMP; 2) if simulated microgravity alters any such LBNP-induced effect; and 3) if simulated microgravity reduces resting plasma cGMP levels. In addition, we studied the time-course of thoracic impedance during, LBNP and asked if there is heart rate/blood pressure reduction after LBNP. During real and simulated spaceflight, blood is re-distributed throughout the vasculature along the body axis, vascular mechanoreceptor loads are altered, "excess" fluid is lost from the organism, and reflexly connected endocrine systems adapt with accompanying changes of hormone output. Altered steady-state plasma concentrations of volume sensitive hormones have been observed inflight as well as postflight. Hormones play a salient role in volume regulation but have barely been studied during microgravitational conditions in conjunction with lower body suction (LBNP). We used LBNP as an analogue to orthostatic stress since this model is useful to investigate, on quantitative grounds, hormone concentration changes as a function of cardiovascular stress in simulated weightless conditions. Earlier we reported consistently reduced plasma ANP and cGMP levels in a case study (14 mo spaceflight); transient hormonal changes after LBNP (as % of pre-LBNP values) were not different (p>0.05) from ground-control findings, and other hormone levels did not consistently deviate from ground control values. This is important since transmural central venous pressure which influences ANP output from the heart, and is elevated despite decreased CVP in parabolic flight, might be downregulated on a long-term basis. TCVP has not yet been measured inflight.