Generation of optimum pseudorandom signals for respiratory impedance measurements

Spontaneous breathing may impair the reliability of forced oscillatory impedance estimates at low frequencies, especially when the oscillatory power is distributed among many frequency values. Since the amplitude of the external forcing is limited to avoid non-linearities, it is suggested that the total energy of a composite electrical signal driving the loudspeaker be maximized at a given amplitude by finding the optimum phase relationships of the signal components, and that the low-frequency components increase in energy at the expense of the less disturbed high-frequency region. In healthy children and adults and in obstructed patients, the coherences and the coefficients of variation of the respiratory system impedance (Z_rs) at 2 and 3 Hz were studied in the case of three test signals of 2–15 Hz bandwidth. Signals T1 and T2 had a flat power spectrum, whereas the components of T3 decreased sharply between 2 and 5 Hz; T1 was generated by simple random selection of phase angles, while optimization for maximum energy was done for T2 and T3. Optimization alone (T2) increased the reliability of the Z_rs estimates at all frequencies, whereas enhancement of the low-frequency power (T3) resulted in a radical improvement of the estimates at 2 and 3 Hz, without loss in reliability at higher frequencies.     

Dielectric relaxation of DNA in aqueous solutions.

Using a four-electrode cell and a new electronic system for direct detection of the frequency differences specturm of solution impedance, the complex dielectric constant of calf thymus DNA (M_r = 4 × 10⁶) in aqueous NaCl at 10°C is measured at frequencies ranging from 0.2 Hz to 30 kHz. The DNA concentrations are C_p = 0.01% and 0.05%, and the NaCl concentrations are varied from C_s = 10^?4 M to 10^?3 M. A single relaxation regions is found in this frequency range, the relaxation frequency being 10 Hz at C_p = 0.01% and C_s = 10^?3 M. At C_p = 0.05% it is evidenced that the DNA chains have appreciable intermolecular interactions. The dielectric relaxaton time τ_d at C_p = 0.01% agrees well with the rotational relaxation time estimated from the reduced visocisty on the assumption that the DNA is not representable as a rigid rod but a coiled chain. It is concluded that the dielectric relaxiatioinis ascribed to the rotation of the molecule. Observed values of dielectric increment and other experimental findings are reasonably explained by assuming that the dipole moment of DNA results from the slow counterion fluctuation which has a longer relaxation time than τ_d.     

Factors affecting electrical impedance of internodal stem sections

A sample holder was designed and built to facilitate measuring the magnitude and phase angle of the electrical impedance of internodal stem sections from Cornus stolonifera Michx. A nonpolarizing, electrically conducting manganese dioxidecarbon paste used between the stem sample and the electrodes of the sample holder allowed measurement of impedance at frequencies from 50 hertz to 500 kilohertz without electrode polarization or electrical interference. The impedance magnitude was linearly dependent on the sample length, but this dependence was minimized by computing a normalized impedance magnitude. The normalized impedance magnitude (Z_nf) was calculated using the impedance magnitude (Z) at any specified frequency (f) and the impedance magnitude at 500 kilohertz (Z_{500 khz}) in the following formula: Z_nf = (Z - Z_{500 khz})/Z_{500 khz}. The normalized impedance magnitude was sensitive to injury produced by boiling and peeling the sample. Electrical impedance measurements on the bark and wood separately demonstrated that they have different electrical properties.     

Frequency-Dependent Release of Acetylcholine and Dopamine From Rabbit Striatum: Its Modulation by Dopaminergic Receptors

Abstract: The release of [³H]dopamine (DA) and [¹⁴C]acetylcholine (ACh) was monitored from single slices of the rabbit striatum. In all cases, the evoked overflow of ACh showed a higher peak and was of shorter duration than that of ³H products. For ACh, the release per pulse showed a marked decline with increasing frequency of stimulation, whereas flat frequency-release curves were obtained for DA. At 0.1 and 1 Hz the evoked overflows of ACh were 15 and 7 times greater, respectively, than those of DA. Haloperidol (0.03 μM) and sulpiride (1 μM) produced large increases in the evoked overflow of DA and ACh at 3 and 10 Hz; little effect was observed at lower frequencies. These results indicate that the frequency-release curves for DA and ACh are different and that at high frequencies the slope of the curves is modified by activation of pre- and postsynaptic DA receptors. Apomorphine inhibited in a concentration-dependent fashion the evoked overflow of DA and ACh; greater inhibition was obtained at lower frequencies of stimulation. At 0.3 Hz the- DA agonist was two times more potent in inhibiting DA than ACh overflow (IC₅₀: 12.0 ± 2.2 versus 22.0 ± 2.8 nM; p < 0.01). The greater sensitivity of pre-than postsynaptic sites to apomorphine was also seen at higher frequencies (3 Hz). Benztropine (1/μ) reduced the evoked overflow of ACh at 10 Hz, and enhanced that of ³H products at all rates of stimulation (0.3–10 Hz). These results suggest that the release of DA and ACh is regulated by dopaminergic receptors. They also indicate that the effects of DA agonists and antagonists and of uptake inhibitors on DA and ACh release are highly dependent on the frequency of stimulation used.     

On the evolution of behavioral reproductive isolation: The Wallace effect

A model of speciation is constructed in which two equally fit but cross-sterile interbreeding species W and C meet in a zone of overlap Z. Within the type W population, which is held at a constant proportion γ of Z by migration from the outside, a mutation arises which causes a partial aversion to individuals of type C. Formulas for the expected frequency of the various possible mating pairs in Z are derived, and an approximation for small aversion is found. The increase in frequency of the mutant gene in the type W population in Z is the found to be approximately pq(1 ? γ)[r₁(1 ? 2p) + r₂p], where p is the relative proportion of the mutant gene in the type W population, q = 1 ? p, and r₁ and r₂ are the aversion probabilities for mutant heterozygotes and homozygotes, respectively. The resulting selective pressure towards behavioral reproductive isolation is discussed.     

Studies of excitable membrane formed on the surface of protoplasmic drops isolated from Nitella III. Impedance of the surface membrane

A protoplasmic drop isolated from an internodal cell of Nitella in an initial solution composed of 70 mM KNO₃, 50 mM NaNO₃ and 5 mM CaCl₂ became electrically excitable when the drop was placed in the final solution containing 0.5 mM KNO₃, 0.5 mM NaCl, 1 mM Ca(NO₃)₂ and 2 mM Mg(NO₃)₂. The electrical impedance of the surface membrane of the drop was measured both in the initial and final solutions at frequencies between 60 Hz and 100 kHz.The impedance and admittance loci of the surface membrane fell on circular arcs. The d.c. resistance R_m°, and the d.c. capacitance C_m° were determined by extrapolating the circular arcs to the low frequency limit. R_m° thus determined was in the range of 50–200 Ω·cm² in the initial solution, and increased to a steady value of 0.4–4.0 kΩ·cm² when the external solution was replaced by the final solution. After the protoplasmic drop was isolated from the internodal cell of Nitella, C_m° decreased monotonically from about 1.5 μF/cm² within 20 min and approached $\text{1.25±0.1 μ}\text{F/cm}{}^2$ both in the initial and final solutions. No appreciable difference was observed for C_m° in these two solutions.The impedance data were discussed in relation to the process of formation of the membrane at the surface of the protoplasmic drop. After the excitable stage was reached, the drop membrane impedance was found to decrease by a factor of 10 during excitation.     

Intracellular Na+ and K+ shifts induced by contractile activities of rat skeletal muscles

The effects of direct and indirect electrical stimulation on intracellular potassium and sodium contents ([K]_i and [Na]_i, respectively) in rat soleus muscle (SOL) and extensor digitorum longus muscle (EDL) were investigated under in vivo conditions. The changes of [K]_i and [Na]_i contents in both muscles which were stimulated indirectly reached respective values at 30 min or 1 hr after the beginning of stimulation, whereas those of EDL stimulated with 60 Hz changed gradually through 2 hr stimulation. The shifts of [K]_i and [Na]_i in EDL occurred during the twitch contraction at considerably lower frequency stimulation (0.5–10 Hz), whereas those in SOL were observed during the tetanus contraction at high frequency stimulation (10–40 Hz). The difference of change in cationic shifts between EDL and SOL under low frequency stimulation was reduced by ouabain treatment, though the difference was still significant. When the muscles were indirectly stimulated 6000 times at 1,5,10 and 20 Hz, the cationic shifts in EDL were greater than those in SOL, extending over all frequencies. It was concluded that such a difference in ionic shift between contracting EDL and SOL may be primarily due to the difference in unidirectional ionic fluxes per stimulation and, secondly, to the difference in Na⁺-K⁺ pump activity.     

The Apolipoprotein E/CI/CII Gene Cluster and Late-Onset Alzheimer Disease

The chromosome 19 apolipoprotein E/CI/CII gene cluster was examined for evidence of linkage to a familial Alzheimer disease (FAD) locus. The family groups studied were Volga German (VG), early-onset non-VG (ENVG; mean age at onset <60 years), and late-onset families. A genetic association was observed between apolipoprotein E (ApoE) allele ε4 and FAD in late-onset families; the ε4 allele frequency was .51 in affected subjects, .37 in at-risk subjects, .11 in spouses, and .19 in unrelated controls. The differences between the ε4 frequencies in affected subjects versus controls and in at-risk subjects versus controls were highly significant (standard normal deviate [Z_SND]) = 7.37, P < 10⁻⁹; and Z_SND = 4.07, P < .00005, respectively). No association between the ε4 allele and FAD was observed in the ENVG or VG groups. A statistically significant allelic association between ε4 and AD was also observed in a group of unrelated subjects; the ε4 frequency was .26 in affected subjects, versus .19 in controls (Z_SND = 2.20, P < .03). Evidence of linkage of ApoE and ApoCII to FAD was examined by maximum-likelihood methods, using three models and assuming autosomal dominant inheritance: (1) age-dependent penetrance, (2) extremely low (1%) penetrance, and (3) age-dependent penetrance corrected for sporadic Alzheimer disease (AD). For ApoCII in late-onset families, results for close linkage were negative, and only small positive lod-score-statistic (Z) values were obtained (model 1, maximum Z [Z_max] = 0.61, recombination fraction [θ] = .30; model 2, Z_max = 0.47, θ = .20). For ApoE in late-onset kindreds, positive Z values were obtained when either allele frequencies from controls (model 1, Z_max = 2.02, θ = .15; model 2, Z_max = 3.42, θ = .05) or allele frequencies from the families (model 1, Z_max = 1.43, θ = .15; model 2, Z_max = 1.70, θ = .05) were used. When linkage disequilibrium was incorporated into the analysis, the Z values increased (model 1, Z_max = 3.17, θ = .23; model 3, Z_max = 1.85, θ = .20). For the ENVG group, results for ApoE and ApoCII were uniformly negative. Affected-pedigree-member analysis gave significant results for the late-onset kindreds, for ApoE (Z_SND = 3.003, P = .003) and ApoCII (Z_SND = 2.319, P = .016), when control allele frequencies were used but not when allele frequencies were derived from the families.     

Low spring constant regulates P-selectin-PSGL-1 bond rupture

Forced dissociation of selectin-ligand bonds is crucial to such biological processes as leukocyte recruitment, thrombosis formation, and tumor metastasis. Although the bond rupture has been well known at high loading rate r_f (≥10² pN/s), defined as the product of spring constant k and retract velocity v, how the low r_f (<10² pN/s) or the low k regulates the bond dissociation remains unclear. Here an optical trap assay was used to quantify the bond rupture at r_f ≤ 20 pN/s with low k (∼10⁻³-10⁻² pN/nm) when P-selectin and P-selectin glycoprotein ligand 1 (PSGL-1) were respectively coupled onto two glass microbeads. Our data indicated that the bond rupture force f retained the similar values when r_f increased up to 20 pN/s. It was also found that f varied with different combinations of k and v even at the same r_f. The most probable force, f*, was enhanced with the spring constant when k < 47.0 × 10⁻³ pN/nm, indicating that the bond dissociation at low r_f was spring constant dependent and that bond rupture force depended on both the loading rate and the mechanical compliance of force transducer. These results provide new insights into understanding the P-selectin glycoprotein ligand 1 bond dissociation at low r_f or k.     

Analysis of all possible combinations of four measurements determining true propagation in arteries

All possible combinations of four measurements of blood pressure, blood flow and vascular diameter are examined by transmission-line theory. It is found that only nine measurement combinations can give the attenuation coefficient γ, reflection coefficient R and characteristic impedance Z₀ simultaneously. At least one pressure measurement must be included. Their general expressions with arbitrary measuring locations are presented, together with some simplified forms which cover all the previous methods. A greater choice of method is thereby made available for use in practice. The results show that, regardless of the measurement locations, all combinations can be solved in the order γ first, R second and Z₀ last.     

Frequency dispersions of human skin dielectrics.

The electrical properties of many biological materials are known to exhibit frequency dispersions. In the human skin, the impedance measured at various frequencies closely describes a circular locus of the Cole-Cole type in the complex impedance plane. In this report, the formative mechanisms responsible for the anomalous circular-arc behavior of skin impedance were investigated, using data from impedance measurements taken after successive strippings of the skin. The data were analyzed with respect to changes in the parameters of the equivalent Cole-Cole model after each stripping. For an exponential resistivity profile (Tregear, 1966, Physical Functions of Skin; Yamamoto and Yamamoto, 1976, Med. Biol. Eng., 14:151--158), the profile of the dielectric constant was shown to be uniform across the epidermis. Based on these results, a structural model has been formulated in terms of the relaxation theory of Maxwell and Wagner for inhomogeneous dielectric materials. The impedance locus obtained from the model approximates a circular are with phase constant alpha = 0.82, which compares favorably with experimental data. At higher frequencies a constant-phase, frequency-dependent component having the same phase constant alpha is also demonstrated. It is suggested that an approximately rectangular distribution of the relaxation time over the epidermal dielectric sheath is adequate to account for the anomalous frequency characteristics of human skin impedance.     

Cardiac output of marmots by the thoracic impedance technique.

Baseline impedance (Z₀) and resistivity of blood were higher for marmots than reported for other species. The transthoracic impedance method was compared to dye dilution and electromagnetic flowmeter procedures for estimation of cardiac output of seven marmots at a range of flows from 40 to 400 ml/min. There was a low, positive, but significant correlation (r = 0.566) found in comparison to dye dilution at outputs measured by the impedance method exceeding 120 ml/min. Correlation was better (r = 0.905) in the comparison between impedance and flowmeter methods.It was concluded that transthoracic impedance provides data that are sufficiently accurate for chronic measurements of stroke volume and cardiac output of this species. The method has the additional advantage of supplying EGG and respiratory data without supplemental connections to the animal preparations.     

Transient Phases of the Isometric Tetanus in Frog's Striated Muscle

In an isometric tetanus in frog's sartorius muscle tension approaches the plateau exponentially with rate constant α. α a depends on sarcomere length, s, and temperature, T, according to the Arrhenius equation See PDF for Equation for temperatures between 1 and 20°C and for sarcomere lengths 2.0–2.8 µm. The energy of activation, E, does not vary significantly with s; E = 13.9 ± 2.4 kcal/mole. A(s) decreases monotonically with s; A(2.1 µm) is about three times greater than A(2.8 µm). Late in relaxation active tension approaches zero exponentially with rate constant r. r decreases exponentially with increasing duration of tetanus, D, from r₀ in a twitch to r_∞ for large D. The rate constant for decrease of r with D increases with s and with T. r₀ and r_∞ obey the Arrhenius equation and decrease with increasing s.     

Dominant side in single-leg stance stability during floor oscillations at various frequencies

Background

We investigated lateral dominance in the postural stability of single-leg stance with anteroposterior floor oscillations at various frequencies.

Methods

Thirty adults maintained a single-leg stance on a force platform for 20 seconds per trial. Trials were performed with no oscillation (static condition) and with anteroposterior floor oscillations (2.5-cm amplitude) at six frequencies: 0.25, 0.5, 0.75, 1.0, 1.25 and 1.5 Hz (dynamic condition). A set of three trials was performed on each leg in each oscillation frequency in random order. The mean speed of the center of pressure in the anteroposterior direction (CoP_ap) was calculated as an index of postural stability, and frequency analysis of CoP_ap sway was performed. Footedness for carrying out mobilizing activities was assessed with a questionnaire.

Results

CoP_ap speed exponentially increased as oscillation frequency increased in both legs. The frequency analysis of CoP_ap showed a peak <0.3 Hz at no oscillation. The frequency components at 0.25-Hz oscillation included common components with no oscillation and those at 1.5-Hz oscillation showed the maximum amplitude among all conditions. Postural stability showed no significant difference between left- and right-leg stance at no oscillation and oscillations ≤1.25 Hz, but at 1.5-Hz oscillation was significantly higher in the right-leg stance than in the left-leg stance. For the lateral dominance of postural stability at individual levels, the lateral difference in postural stability at no oscillation was positively correlated with that at 0.25-Hz oscillation (r = 0.51) and negatively correlated with that at 1.5-Hz oscillation (r = -0.53). For 70% of subjects, the dominant side of postural stability was different at no oscillation and 1.5-Hz oscillation. In the subjects with left- or right-side dominance at no oscillation, 94% or 38% changed their dominant side at 1.5-Hz oscillation, with a significant difference between these percentages. In the 1.5-Hz oscillation, 73% of subjects had concordance between the dominant side of postural stability and that of mobilizing footedness.

Conclusion

In static conditions, there was no lateral dominance of stability during single-leg stance. At 1.5-Hz oscillation, the highest frequency, right-side dominance of postural stability was recognized. Functional role in supporting leg may be divided between left and right legs according to the change of balance condition from static to dynamic.     

Influence of sodium concentration on changes of membrane capacitance associated with the electrogenic ion transport by the Na,K-ATPase

Electrogenic ion transport by the Na,K-ATPase was investigated in a model system of protein-containing membrane fragments adsorbed to a lipid bilayer. Transient Na⁺ currents were induced by photorelease of ATP from inactive caged ATP. This process was accompanied by a capacitance change of the membrane system. Two methods were applied to measure capacitances in the frequency range 1 to 6000 Hz. The frequency dependent capacitance increment, ΔC, was of sigmoidal shape and decreased at high frequencies. The midpoint frequency, f ₀, depended on the ionic strength of the buffer. At 150 mm NaCl f ₀ was about 200 Hz and decreased to 12 Hz at high ionic strength (1 M). At low frequencies (f≪f ₀) the capacitance increment became frequency independent. It was, however, dependent on Na⁺ concentration and on the membrane potential which was generated by the charge transferred. A simple model is presented to analyze the experimental data quantitatively as a function of two parameters, the capacitance of the adsorbed membrane fragments, C _P, and the potential of maximum capacitance increment, ψ ₀. Below 5 mm Na⁺ a negative capacitance change was detected which may be assigned to electrogenic Na⁺ binding to cytoplasmic sites. It could be shown that the results obtained by experiments with the presented alternating current method contain the information which is determined by current-relaxation experiments with cell membranes. Received: 3 November 1997 / Revised version: 19 February 1998 / Accepted: 21 February 1998     

Frequency-dependent shear impedance of the tectorial membrane

Microscale mechanical probes were designed and bulk-fabricated for applying shearing forces to biological tissues. These probes were used to measure shear impedance of the tectorial membrane (TM) in two dimensions. Forces were applied in the radial and longitudinal directions at frequencies ranging from 0.01-9 kHz and amplitudes from 0.02-4 μN. The force applied was determined by measuring the deflection of the probes’ cantilever arms. TM impedance in the radial direction had a magnitude of 63 ± 28 mN · s/m at 10 Hz and fell with frequency by 16 ± 0.4 dB/decade, with a constant phase of −72 ± 6°. In the longitudinal direction, impedance was 36 ± 9 mN · s/m at 10 Hz and fell by 19 ± 0.4 dB/decade, with a constant phase of −78 ± 4°. Impedance was nearly constant as a function of force except at the highest forces, for which it fell slightly. These results show that the viscoelastic properties of the TM extend over a significant range of audio frequencies, consistent with a poroelastic interpretation of TM mechanics. The shear modulus G′ determined from these measurements was 17-50 kPa, which is larger than in species with a lower auditory frequency range. This value suggests that hair bundles cannot globally shear the TM, but most likely cause bulk TM motion.     

Effect of Frequency and Waveform on Inactivation of Escherichia coli O157:H7 and Salmonella enterica Serovar Typhimurium in Salsa by Ohmic Heating

The effect of frequency of alternating current during ohmic heating on electrode corrosion, heating rate, inactivation of food-borne pathogens, and quality of salsa was investigated. The impact of waveform on heating rate was also investigated. Salsa was treated with various frequencies (60 Hz to 20 kHz) and waveforms (sine, square, and sawtooth) at a constant electric field strength of 12.5 V/cm. Electrode corrosion did not occur when the frequency exceeded 1 kHz. The heating rate of the sample was dependent on frequency up to 500 Hz, but there was no significant difference (P > 0.05) in the heating rate when the frequency was increased above 1 kHz. The electrical conductivity of the sample increased with a rise in the frequency. At a frequency of 60 Hz, the square wave produced a lower heating rate than that of sine and sawtooth waves. The heating rate between waveforms was not significantly (P > 0.05) different when the frequency was >500 Hz. As the frequency increased, the treatment time required to reduce Escherichia coli O157:H7 and Salmonella enterica serovar Typhimurium to below the detection limit (1 log CFU/g) decreased without affecting product quality. These results suggest that ohmic heating can be effectively used to pasteurize salsa and that the effect of inactivation is dependent on frequency and electrical conductivity rather than waveform.     

Frequency responses of cat rapidly adapting mechanoreceptive fibers

The frequency responses of 11 rapidly adapting (RA) fibers in cat were studied by representing the average firing rate as a function of sinusoidal stimulus amplitude and stimulus frequency. Specifically, rate-intensity functions at different stimulation frequencies were fitted by four-parameter (a₀, a₁, a₂, a₃), piece-wise linear functions using nonlinear regression (n = 59; R² > 0.877). Rate-intensity functions at intermediate frequencies were found by linear interpolation. The result of this analysis is rate–amplitude–frequency functions plotted as two-dimensional surfaces. The surfaces consist of five regions separated and sufficiently defined by four space curves. At 14 different frequencies, the statistical distribution of each rate-intensity-function parameter could be approximated by a particular lognormal distribution (n = 56; R² > 0.796). The Kolmogorov–Smirnov test fails to reject this hypothesis for each combination of frequency and parameter (56 tests; p > 0.39). Therefore, at a given frequency, the variation of the parameters can be represented by lognormal distributions with specific means and standard deviations. Responses of six RA fibers, which are different from the data-set used for modeling, were compared with the stochastic model at different frequencies. The parameters of those fibers were tested against the null hypotheses that they were sampled from the particular parameter distributions dictated by the model. The Kolmogorov–Smirnov test fails to reject all the hypotheses at the α = 0.05 level (44 tests). At the α = 0.10 level, only a few test parameters were found to be departing from the model (a₀ and a₁ at 5?Hz; a₂ at 20?Hz; a₂ and a₃ at 50?Hz). The remaining test parameters could be accurately described by the model. Having confirmed the validity of the model, the logarithmic means and the logarithmic standard deviations of the lognormally distributed rate-intensity-function parameters were estimated in the frequency range of 4–200?Hz. The rate–amplitude–frequency surfaces sampled from the established stochastic model completely characterize the rate responses of RA fibers to sinusoidal stimuli and are superior to tuning curves which require selecting criterion responses. The current rate-response model is promising for future computational work, especially on population modeling.     

On‐Chip MXene Microsupercapacitors for AC‐Line Filtering Applications

Microsupercapacitors (MSCs) with high energy densities offer viable miniaturized alternatives to bulky electrolytic capacitors if the former can respond at the kilo Hertz (kHz) or higher frequencies. Moreover, MSCs fabricated on a chip can be integrated into thin‐film electronics in a compatible manner, serving the function of ripple filtering units or harvesters of energy from high‐frequency sources. In this work, wafer‐scale fabrication is demonstrated of MXene microsupercapacitors with controlled flake sizes and engineered device designs to achieve excellent frequency filtering performance. Specifically, the devices (100 nm thick electrodes and 10 µm interspace) deliver high volumetric capacitance (30 F cm^?3 at 120 Hz), high rate capability (300 V s^?1), and a very short relaxation time constant (τ₀ = 0.45 ms), surpassing conventional electrolytic capacitors (τ₀ = 0.8 ms). As a result, the devices are capable of filtering 120 Hz ripples produced by AC line power at a frequency of 60 Hz. This study opens new avenues for exploring miniaturized MXene MSCs as replacements for bulky electrolytic capacitors.     

Patchy deletion of Bmpr1a potentiates proximal pulmonary artery remodeling in mice exposed to chronic hypoxia

Reduced vascular expression of bone morphogenetic protein type IA receptor (Bmpr1a) has been found in patients with pulmonary arterial hypertension. Our previous studies in mice with patchy deletion of Bmpr1a in vascular smooth muscle cells and cardiac myocytes showed decreased distal vascular remodeling despite a similar severity of hypoxic pulmonary hypertension (HPH). We speculate increased stiffness from ectopic deposition of collagen in proximal pulmonary arteries might account for HPH. Pulsatile pressure-flow relationships were measured in isolated, ventilated, perfused lungs of SM22α;TRE-Cre;R26R;Bmpr1a ^flox/flox (KO) mice and wild-type littermates, following 21 days (hypoxia) and 0 days (control) of chronic hypoxia. Pulmonary vascular impedance, which yields insight into proximal and distal arterial remodeling, was calculated. Reduced Bmpr1a expression had no effect on input impedance Z ₀ (P = 0.52) or characteristic impedance Z _C (P = 0.18) under control conditions; it also had no effect on the decrease in Z ₀ via acute rho kinase inhibition. However, following chronic hypoxia, reduced Bmpr1a expression increased Z _C (P < 0.001) without affecting Z ₀ (P = 0.72). These results demonstrate that Bmpr1a deficiency does not significantly alter the hemodynamic function of the distal vasculature or its response to chronic hypoxia but larger, more proximal arteries are affected. In particular, reduced Bmpr1a expression likely decreased dilatation and increased stiffening in response to hypoxia, probably by collagen accumulation. Increased PA stiffness can have a significant impact on right ventricular function. This study illustrates for the first time how proximal pulmonary artery changes in the absence of distal pulmonary artery changes contribute to pulmonary arterial hypertension.