Guide to Community Preventive Services: a commentary.
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Health Planning↗
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Results for “Value Orientation--changes”
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Redox components of cytochrome bc-type enzymes in acidophilic prokaryotes. II. The Rieske protein of phylogenetically distant acidophilic organisms.
The Rieske proteins of two phylogenetically distant acidophilic organisms, i.e. the proteobacterium Thiobacillus ferrooxidans and the crenarchaeon Sulfolobus acidocaldarius, were studied by EPR. Redox titrations at a range of pH values showed that the Rieske centers of both organisms are characterized by redox midpoint potential-versus-pH curves featuring a common pK value of 6.2. This pK value is significantly more acidic (by almost 2 pH units) than that of Rieske proteins in neutrophilic species. The orientations of the Rieske center's g tensors with respect to the plane of the membrane were studied between pH 4 and 8 using partially ordered samples. At pH 4, the Sulfolobus Rieske cluster was found in the "typical" orientation of chemically reduced Rieske centers, whereas this orientation changed significantly on going toward high pH values. The Thiobacillus protein, by contrast, appeared to be in the "standard" orientation at both low and high pH values. The results are discussed with respect to the molecular parameters conveying acid resistance and in light of the recently demonstrated long-range conformational movement of the Rieske protein during enzyme turnover in cytochrome bc1 complexes.
Cytochrome b Group↗
Decreases in frontal and parietal lobe regional cerebral blood flow related to habituation.
We previously reported decreased mean CBF between consecutive resting conditions, ascribed to habituation. Here we address the regional specificity of habituation over three consecutive flow studies. Regional CBF (rCBF) was measured in 55 adults (12 right-handed men, 12 right-handed women, 14 left-handed men, 17 left-handed women), with the 133Xe inhalation technique, during three conditions: resting, verbal tasks (analogies), and spatial tasks (line orientation). Changes in rCBF attributable to the cognitive tasks were eliminated by correcting these values to a resting equivalent. There was a progressive decrease in mean rCBF over time, reflecting habituation. This effect differed by region, with specificity at frontal (prefrontal, inferior frontal, midfrontal, superior frontal) and inferior parietal regions. In the inferior parietal region, habituation was more marked in the left than the right hemisphere. Right-handers showed greater habituation than did left-handers. There was no sex difference in global habituation, but males showed greater left whereas females showed greater right hemispheric habituation. The results suggest that habituation to the experimental setting has measurable effects on rCBF, which are differently lateralized for men and women. These effects are superimposed on task activation and are most pronounced in regions that have been implicated in attentional processes. Thus, regional decrement in brain activity related to habituation seems to complement attentional effects, suggesting a neural network for habituation reciprocating that for attention.
Adult↗
Glycosphingolipids: 2H NMR study of the influence of carbohydrate headgroup structure on ceramide acyl chain behavior in glycolipid-phospholipid bilayers.
Galactosyl- and glucosylceramide, globoside, and dihydrolactosylceramide, bearing [2,2-2H2]stearic acid, have been studied at a concentration of 10 mol% in bilayers of dimyristoylphosphatidylcholine by 2H NMR. The quadrupolar splitting delta vQ of the C2 deuterons were measured at several temperatures in the range of 30-60 degrees C. Spin-lattice relaxation times T1 of C2 deuterons were determined in the same temperature range for all lipids but globoside. T1 values at 30 and 50 degrees C were unexpectedly short (6-8 ms), indicating reduced mobility of the ceramide acyl chains compared to that of the host phospholipid. At all temperatures, both delta vQ and T1 were essentially identical for the monoglycosylated species, GalCer and GlcCer, indicating that the order and dynamics of the upper portion of the fatty acyl chain are insensitive to this small change in the headgroup structure. In the case of globoside, where the glycolipid headgroup is equivalent to that of GlcCer extended by three sugar residues, values for the quadrupolar splittings associated with the acyl chain C2-position were very close to those obtained for Gal- and GlcCer. In contrast, the delta vQ values obtained for the diglycosyl species, LacCer, were significantly different at all temperatures. This different behavior of LacCer relative to that of the other glycolipids most likely originates from an orientational change of the acyl chain at the C2-position due to the absence of a 4,5 double bond in dihydrosphingosine. T1 values for the GlcCer and GalCer systems increased with temperature, indicating that the motions responsible for relaxation were in the short correlation time regime.(ABSTRACT TRUNCATED AT 250 WORDS)
Ceramides↗
A possible orientation change of cardiotoxin molecule during its interaction with phospholipid monolayer.
The monomolecular film technique was used in order to study the specific interactions of 4 cardiotoxins from Elapidae snake venom Naja mossambica mosambica with different phospholipids. The interaction, at pH 7.5, of cardiotoxin (10(-7) M) with both neutral and negatively charged phospholipids occurs up to a very high critical surface pressure (pi = 45 dynes/cm with the latest). The apparent molecular area of cardiotoxin molecule, during its insertion into a negatively charged phospholipid film, presents only two characteristic values: 1400 A2 for pi less than 20 dynes/cm and 420 A2 for pi greater than 30 dynes/cm, the transition occurring in a very narrow range of surface pressure (25 +/- 5 dynes/cm). Thus, according to the surface pressure, the cardiotoxin may present two different orientations: "flat" or "edgewise" and the transition between both could account for lytic activity of cardiotoxin.
Cobra Cardiotoxin Proteins↗
Electro-optics of membrane electroporation in diphenylhexatriene-doped lipid bilayer vesicles.
The electric (linear) dichroisms observed in the membrane electroporation of salt-filled lipid bilayer vesicles (diameter O = 2 alpha = 0.32 micron; inside [NaCl] = 0.2 M) in isotonic aqueous 0.284 M sucrose-0.2 mM NaCl solution indicate orientation changes of the anisotropic light scattering centers (lipid head groups) and of the optical transition moments of the membrane-inserted probe 1,6-diphenyl-1,3,5-hexatriene (DPH). Both the turbidity dichroism and DPH absorbance dichroism show peculiar features: (1) at external electric fields E > or = Esat the time course of the dichroism shows a maximum value (reversal): Esat = 4.0 (+/- 0.2) MV m-1, T = 293 K (20 degrees C), (2) this reversal value is independent of the field strength for E > or = Esat, (3) the dichroism amplitudes exhibit a maximum value Emax = 3.0 (+/- 0.5) MV m-1, (4) for the pulse duration of 10 microseconds there is one dominant visible normal mode, the relaxation rate increases up to tau-1 approximately 0.6 x 10(6) s-1 at Esat and then decreases for E > Esat. The data can be described in terms of local lipid phase transitions involving clusters Ln of n lipids in the pore edges according to the three-state scheme C<-->HO<-->HI, C being the closed bilayer state, HO the hydrophobic pore state and HI the hydrophilic or inverted pore state with rotated lipid and DPH molecules. At E > or = Esat, further transitions HO<-->HO* and HI<-->HI* are rapidly coupled to the C<-->HO transition, which is rate-limiting. The vesicle geometry conditions a cos theta dependence of the local membrane field effects relative to the E direction and the data reflect cos theta averages. The stationary induced transmembrane voltage delta phi (theta, lambda m) = -1.5 aEf(lambda m) magnitude of cos theta does not exceed the limiting value delta phi sat = -0.53 V, corresponding to the field strength Em,sat = -delta phi sat/d = 100 MV m-1 (10(3) kV cm-1), due to increasing membrane conductivity lambda m. At E = Esat, f(lambda m) = 0.55, lambda m = 0.11 mS m-1. The lipid cluster phase transition model yields an average pore radius of rp = 0.35 (+/- 0.05) nm of the assumed cylindrical pore of thickness d = 5 nm, suggesting an average cluster size of = 12 (+/- 2) lipids per pore edge. For E > Esat, the total number of DPH molecules in pore states approaches a saturation value; the fraction of DPH molecules in HI pores is 12 (+/- 2)% and that in HO pores is 48 (+/- 2)%. The percentage of membrane area P approximately (lambda m/lambda i) x 100% of conductive openings filled with the intravesicular medium of conductance lambda i = 2.2 S m-1 linearly increases from P approximately 0% (E = 1.8 MV m-1) to P = 0.017% (E = 8.5 MV m-1). Analogous estimations made by Kinosita et al. (1993) on the basis of fluorescence imaging data for sea urchin eggs give the same order of magnitude for P (0.02-0.2%). The increase in P with the field strength is collinear with the increase in concentration of HI and HI* states with the field strength, whereas the HO and HO* states exhibit a sigmoid field dependence. Therefore our data suggest that it is only the HI and HI* pore states which are conductive. It is noted that the various peculiar features of the dichroism data cannot be described by simple whole particle deformation.
Chemical Phenomena↗
Motion detection in the presence of local orientation changes.
To investigate the orientation selectivity of motion detectors, we measured the perception of horizontal apparent motion of dense patterns of line elements with randomized orientation. Horizontal motion of these displays became invisible when the simultaneous rotation of the line elements exceeded a critical rate (pc). The value of pc increased for higher horizontal velocities, approximately according to a square-root relation. In a direct test of orientation selectivity, the discrimination of horizontal motion direction disappeared when the orientation change per horizontal jump exceeded 30 deg. Thus, for the perception of the global flow the orientation change should not exceed a critical angle during the traverse of a critical distance. The critical distance increases according to a square-root relation as a function of horizontal velocity. These results strongly suggest that bilocal motion detectors are involved in horizontal motion detection and that these detectors are selective for orientation. The properties of these detectors, such as the orientation sensitivity that is reported in this paper, seem highly relevant to the perception of coherent motion.
Humans↗
A quantitative approach to cytoarchitectonics: software and hardware aspects of a system for the evaluation and analysis of structural inhomogeneities in nervous tissue.
Cytoarchitectonic studies are based on the analysis of structural inhomogeneities in nervous tissue. Boundaries of brain regions are established where local structural properties such as numerical cell density, size, shape or orientation change. The measurement of these properties from histological sections with automatic devices is biased due to the thickness of the sections. In this study, the grey level index (GLI) is measured with a TV-based image analyzer from routine histological sections. This parameter is a biased estimate of the volume density of Nissl-positive structures. The histological section is digitized into GLI values by a computer-controlled scanning procedure. The result is stored in an image matrix which is processed by digital filtering in order to visualize the laminar pattern. GLI statistics of brain regions are evaluated from the pictorial data by delineating these regions with a cursor on a hard copy fixed to digitizer. Information from a series of sections is stored in a standardized data file and combined by specific application programs.
Animals↗
Fast-scan cyclic voltammetry of protein films on pyrolytic graphite edge electrodes: characteristics of electron exchange.
The rapid electron-exchange characteristics of metalloproteins adsorbed at a pyrolytic graphite "edge" electrode have been studied by analog dc cyclic voltammetry at scan rates up to 3000 V s-1. The voltammetry of four proteins, azurin (a "blue" copper protein) and three 7Fe ferredoxins, reveals oxidation and reduction peaks that display only modest increases in width and peak separation as the scan rate is raised. This is indicative of a substantially homogeneous population of noninteracting centers which undergo rapid electron exchange with the electrode. Both the Butler--Volmer and Marcus models have been tested. The electrochemical kinetics, as reflected by k0 (the rate at zero overpotential), are too fast to allow the determination of reorganization energies by this method. Nonetheless, the rapid and energetically coherent nature of the electron transfer enables the cyclic oxidation and reduction of protein redox centers to be examined on a time scale sufficiently short to recognize coupled processes occurring in the millisecond time domain, which are characteristic of the protein under investigation. Two of the ferredoxins display increasingly asymmetric voltammetry as the scan rate is increased, which is attributed to the coupling of electron transfer to conformational (or orientational) changes. For azurin, the use of higher electrolyte concentrations enables studies to be made at scan rates up to 3000 V s-1, from which a standard electron-transfer rate constant in the region of 5000 s-1 is obtained. At these high scan rates, azurin still shows very symmetrical voltammograms but with peak shapes displaying a more gradual decrease in current, at increasing overpotential, than is predicted using realistic values of the reorganization energy. The ability to measure even faster rate constants and access coupled reactions occurring in shorter time domains is likely to be limited by complex processes occurring on the graphite surface.
Archaeal Proteins↗
Structure and dynamics of melittin in lysomyristoyl phosphatidylcholine micelles determined by nuclear magnetic resonance.
Mixed micelles of the 26-residue, lytic peptide melittin (MLT) and 1-myristoyl-2-hydroxyl-sn-glycero-3-phosphocholine (MMPC) in aqueous solution at 25 degrees C were investigated by (13)C- and (31)P-NMR spectroscopy. (13)C alpha chemical shifts of isotopically labeled synthetic MLT revealed that MLT in the micelle is predominantly alpha-helical and that the peptide secondary structure is stable from pH 4 to pH 11. Although the helical transformation of MLT as determined from NMR is evident at lipid:peptide molar ratios as low as 1:2, tryptophan fluorescence measurements demonstrate that well-defined micellar complexes do not predominate until lipid:peptide ratios exceed 30:1. (31)P linewidth measurements indicate that the interaction between phosphate ions in solution and cationic groups on MLT is pH dependent, and that the phosphoryl group of MMPC senses a constant charge, most likely +2, on MLT from pH 4 to pH 10. (13)C-NMR relaxation data, analyzed using the model-free formalism, show that the peptide backbone of MLT is partially, but not completely, immobilized in the mixed micelles. Specifically, order parameters (S(2)) of C alpha-H vectors averaged 0.7 and were somewhat larger for residues in the N-terminal half of the molecule. The amino terminal glycine had essentially the same range of motion as the backbone carbons. Likewise, order parameters for the trp side chain were similar to those found for the peptide C alpha moieties, as was verified by trp fluorescence anisotropy decay data. In contrast, the motion of the lysine side chains was less restricted, the average S(2) values for the C epsilon-H vectors being 0.19, 0.30, and 0.44 for lys-7, 21, and 23, respectively, for MLT in the mixed micelles. Values of the effective correlation time of the local motion tau e were in the motional narrowing limit and usually longer for side-chain atoms than for those in the backbone. The dynamics were independent of pH from pH 4 to pH 9, but at pH 11 the correlation time for the rotational motion of the mixed micelles as a whole increased from 10 ns to 16 ns, and S(2) for the lys side chains increased. Overall it appears that the MLT helix lies near the surface of the micelle at low to neutral pH, but at higher pH its orientation changes, accompanied by deeper penetration of the lysine side chains into the micelle interior. It is apparent, however, that the MLT-lipid interaction is not dependent on deprotonation of any of the titratable cationic groups in the peptide in the pH 4-10 range, and that there is substantial backbone and side-chain mobility in micelle-bound MLT.
Amino Acid Sequence↗
Orientation changes in myosin regulatory light chains following photorelease of ATP in skinned muscle fibers.
The orientation of the light-chain region of myosin heads in muscle fibers was followed by polarized fluorescence from an extrinsic probe during tension transients elicited by photolysis of caged ATP. Regulatory light chain from chicken gizzard myosin was covalently modified with iodoacetamidotetramethylrhodamine and exchanged into skinned fibers from rabbit psoas muscle without significant effect of the tension transients. Fluorescence polarization ratios Q parallel = (parallel I parallel-perpendicular I parallel)/ (parallel I parallel+perpendicular I parallel) and Q perpendicular = perpendicular I perpendicular - parallel I perpendicular)/ (perpendicular I perpendicular + parallel I perpendicular), where mIn denote fluorescence intensities for excitation (pre-subscript) and emission (post-subscript) parallel or perpendicular to the fiber axis, were simultaneously measured at 0.5 ms time resolution. Q perpendicular decreased and Q parallel increased promptly after ATP release in the presence or absence of CA2+, indicating changes in orientation of the light-chain region associated with ATP binding or cross-bridge detachment. Little further change in the Q signals accompanied either active tension development (+Ca2+) or the final relaxation (-Ca2+). The Q and tension transients slowed when liberated ATP concentration was reduced. Assuming that ATP is released at 118 s-1 (20 degrees C), the apparent second-order rate constants were 3-10 x 10(5) M-1 s-1 for Q parallel, 1-5 x 10(5) M-1 s-1 for Q perpendicular, and 0.5-2 x 10(5) M-1 s-1 for the convergence of tension traces starting from different rigor values. Fitting of model orientation distributions to the Q signals indicated that the angular disorder increases after ATP binding. This orientation change is specific to ATP because photo release of ADP caused much smaller changes in the Q signals.
Adenosine Diphosphate↗
Time-varying activation of different cytoarchitectonic areas of the human SI cortex after tibial nerve stimulation.
We followed cortical activation in eight healthy adults after electric stimulation of the left tibial nerve at the ankle. The recordings were made noninvasively with a whole-scalp neuromagnetometer. The first cortical activation peaked in different subjects at 37-45 ms in the foot area of the right (contralateral) primary somato-sensory (SI) cortex, with mean source current orientation perpendicular to the longitudinal fissure. The current orientation changed within the next 5 ms counterclockwise in all subjects, with a mean rotation of 64 degrees. A two-dipole time-varying model, with two dipoles differing by 28-119 degrees in orientation but less than 1 cm in location in the right SI cortex, explained the signal pattern satisfactorily during the first 100 ms. We suggest that the observed field patterns reflect sequential activation of different cytoarchitectonic areas in the foot SI cortex and imply considerable differences in the structural organization between the foot and the hand SI cortices. The initial activation is considered to take place in area 3b facing the interhemispheric fissure, and the later source, due to the systematic rotations of the field patterns, is assumed to reflect activation of area 5 in the anterior wall of the marginal ramus of the cingulate sulcus.
Adult↗
Orientation discrimination sensitivity of single units in cat primary visual cortex.
Responses of visual cortex (area 17) neurons to moving oriented stimuli were recorded from anesthetized cats. The variance of response (SD2) to repeated identical stimuli was directly proportional to response magnitude (R), (SD2 = C2R). The values of C were not found to differ significantly between different types of cortical cells. The relationship predicts that the coefficient of variation (SD/R) will be smallest near the peak of the tuning curve, indicating that the peak response is most reliable for detecting an orientation but not necessarily the most sensitive to a change in orientation. Tuning curves and response variability were then examined to determine the orientation at which the neuron was most sensitive to changes in stimulus orientation using signal detection theory. The discrimination index (d' = [R1-R2]/SD) for a 1 degree change in stimulus orientation was greatest along the flanks of the tuning curve. In order to generalize the experimental data, response distributions derived from a model of cells with parameters based on experimental data were examined to determine the minimal discriminable change in stimulus orientation. Changes of stimulus orientation between 0.6 and 5 deg of arc could be detected from single responses of a single cell by an optimal observer with 75% accuracy if the orientation change was centered at the most sensitive part of the tuning curve.
Action Potentials↗
Fluorescence polarization transients from rhodamine isomers on the myosin regulatory light chain in skeletal muscle fibers.
Fluorescence polarization was used to examine orientation changes of two rhodamine probes bound to myosin heads in skeletal muscle fibers. Chicken gizzard myosin regulatory light chain (RLC) was labeled at Cys108 with either the 5- or the 6-isomer of iodoacetamidotetramethylrhodamine (IATR). Labeled RLC (termed Cys108-5 or Cys108-6) was exchanged for the endogenous RLC in single, skinned fibers from rabbit psoas muscle. Three independent fluorescence polarization ratios were used to determine the static angular distribution of the probe dipoles with respect to the fiber axis and the extent of probe motions on the nanosecond time scale of the fluorescence lifetime. We used step changes in fiber length to partially synchronize the transitions between biochemical, structural, and mechanical states of the myosin cross-bridges. Releases during active contraction tilted the Cys108-6 dipoles away from the fiber axis. This response saturated for releases beyond 3 nm/half-sarcomere (h.s.). Stretches in active contraction caused the dipoles to tilt toward the fiber axis, with no evidence of saturation for stretches up to 7 nm/h.s. These nonlinearities of the response to length changes are consistent with a partition of approximately 90% of the probes that did not tilt when length changes were applied and 10% of the probes that tilted. The responding fraction tilted approximately 30 degrees for a 7.5 nm/h.s. release and traversed the plane perpendicular to the fiber axis for larger releases. Stretches in rigor tilted Cys108-6 dipoles away from the fiber axis, which was the opposite of the response in active contraction. The transition from the rigor-type to the active-type response to stretch preceded the main force development when fibers were activated from rigor by photolysis of caged ATP in the presence of Ca2+. Polarization ratios for Cys108-6 in low ionic strength (20 mM) relaxing solution were compatible with a combination of the relaxed (200 mM ionic strength) and rigor intensities, but the response to length changes was of the active type. The nanosecond motions of the Cys108-6 dipole were restricted to a cone of approximately 20 degrees half-angle, and those of Cys108-5 dipole to a cone of approximately 25 degrees half-angle. These values changed little between relaxation, active contraction, and rigor. Cys108-5 showed very small-amplitude tilting toward the fiber axis for both stretches and releases in active contraction, but much larger amplitude tilting in rigor. The marked differences in these responses to length steps between the two probe isomers and between active contraction and rigor suggest that the RLC undergoes a large angle change (approximately 60 degrees) between these two states. This motion is likely to be a combination of tilting of the RLC relative to the fiber axis and twisting of the RLC about its own axis.
Animals↗
Reorientations in the bacteriorhodopsin photocycle.
Reversible photoinduced reorientations of bacteriorhodopsin have been detected in suspensions of the purple membrane of Halobacterium salinarium. The anisotropy in bacteriorhodopsin during the nanosecond through millisecond stages of the photocycle was measured by time-resolved linear dichroism and transient absorption measurements. From these measurements the anisotropies of the K, L, M, and O intermediates were determined and related to the chromophore orientation with respect to the initially selected orientation. The anisotropies of the K and L states are 0.38 +/- 0.01 and 0.35 +/- 0.01, respectively. Further anisotropy decay after formation of the M intermediate in about 0.5 ms is evidence of orientational motion at this stage in the photocycle. A constant anisotropy with a value of 0.39 +/- 0.02 in the O intermediate demonstrates a recovery of the initial protein orientation with the formation of the O state. These results demonstrate that reorientations in BR are photoinduced and reversible. Similar measurements for L and M were carried out for purple membrane in polyacrylamide gels, where the anisotropies in the L and M states are 0.38 +/- 0.014 and 0.36 +/- 0.01, respectively. These results show that reorientations also occur in BR immobilized in gels. Anisotropy decay in the M state after formation of the M intermediate was not detected in the gels, in contrast to the M intermediate in suspensions. Orientational changes are observed for BR in purple membrane suspensions in the K state, during the K-->L step, in the M state possibly related to an M1-->M2 transition, and in the O state, where an almost complete return to the original orientation occurs.(ABSTRACT TRUNCATED AT 250 WORDS)
Acrylic Resins↗
Effects of size and orientation change on hippocampal activation during episodic recognition: a PET study.
To determine whether physical match between studied and tested items influences blood flow increases in the hippocampal formation associated with recognition memory, positron emission tomography (PET) was used to measure changes in regional cerebral blood flow while healthy volunteers made old/new judgements about line drawings of objects. Some objects were tested in the same size and orientation as they had appeared earlier during the study phase of the experiment; other objects were tested in a different size or orientation than when they were studied. Blood flow increases in the vicinity of the hippocampal formation were observed in the same object condition compared with the size change and the orientation change conditions, even though recognition accuracy was affected significantly only by orientation change. Results add to previous findings suggesting that physical similarity between studied items and test cues may contribute to hippocampal activation during episodic retrieval.
Adult↗
Heart rate signal decomposition.
This paper proposes a method for decomposing heart rate fluctuations into background, respiratory and blood pressure oriented fluctuations. A signal cancellation scheme using the adaptive RLS algorithm has been introduced for cancelling respiration and blood pressure oriented changes in the heart rate fluctuations. The computer simulation confirmed the validity of the proposed method. Then, heart rate fluctuations, instantaneous lung volume and blood pressure changes are simultaneously recorded from eight normal subjects aged 20-24 years. It was shown that after signal decomposition, the power spectrum of the heart rate showed a consistent monotonic 1/fa type pattern. The proposed method enables a clear interpretation of heart rate spectrum removing uncertain large individual variations due to the respiration and blood pressure change.
Adult↗
Plasma renin activity, aldosterone and cortisol in relation with postural changes in dogs.
Experiments were carried out in six dogs anesthetized with chloralose, fixed on a tilting table and moved from the supine to the vertical posture. In one dog this postural change was done after cutting both Hering nerves, and in another one after bilateral nephrectomy (BN), these experiments being orientative. Changing the supine to the vertical posture was followed by increase in plasma renin activity (PRA) and in aldosterone and cortisol plasma concentration (p.c.) Between PRA and aldosterone p.c., there was a slight correlation, but between aldosterone and cortisol this was evident. Therefore it may be supposed that aldosterone hypersecretion is produced by ACTH hypersecretion, a common stimulatory pathway for both hormones. This stimulatory mechanism is sustained by the orientative experiment on dogs, with BN, in which supine to vertical changed posture was followed by an important aldosterone hypersecretion despite minimal values of PRA.
Aldosterone↗