Beschreibung: Background— Inorganic nitrite dilates small resistance arterioles via hypoxia-facilitated reduction to vasodilating nitric oxide. The effects of nitrite in human conduit arteries have not been investigated. In contrast to nitrite, organic nitrates are established selective dilators of conduit arteries. Methods and Results— We examined the effects of local and systemic administration of sodium nitrite on the radial artery (a muscular conduit artery), forearm resistance vessels (forearm blood flow), and systemic hemodynamics in healthy male volunteers (n=43). Intrabrachial sodium nitrite (8.7 μmol/min) increased radial artery diameter by a median of 28.0% (25th and 75th percentiles, 25.7% and 40.1%; P 〈0.001). Nitrite (0.087–87 μmol/min) displayed conduit artery selectivity similar to that of glyceryl trinitrate (0.013–4.4 nmol/min) over resistance arterioles. Nitrite dose-dependently increased local cGMP production at the dose of 2.6 μmol/min by 1.1 pmol·min –1 ·100 mL –1 tissue (95% confidence interval, 0.5–1.8). Nitrite-induced radial artery dilation was enhanced by administration of acetazolamide (oral or intra-arterial) and oral raloxifene ( P =0.0248, P 〈0.0001, and P =0.0006, respectively) but was inhibited under hypoxia ( P 〈0.0001) and hyperoxia ( P =0.0006) compared with normoxia. Systemic intravenous administration of sodium nitrite (8.7 μmol/min) dilated the radial artery by 10.7% (95% confidence interval, 6.8–14.7) and reduced central systolic blood pressure by 11.6 mm Hg (95% confidence interval, 2.4–20.7), augmentation index, and pulse wave velocity without changing peripheral blood pressure. Conclusions— Nitrite selectively dilates conduit arteries at supraphysiological and near-physiological concentrations via a normoxia-dependent mechanism that is associated with cGMP production and is enhanced by acetazolamide and raloxifene. The selective central blood pressure–lowering effects of nitrite have therapeutic potential to reduce cardiovascular events.

Beschreibung: Arterial tone in muscular conduit arteries may influence pressure wave reflection through changes in diameter and pulse wave velocity. We examined the relative specificity of vasodilator drugs for radial artery and forearm resistance vessels during intrabrachial arterial infusion. The nitric oxide (NO) donors, nitroglycerine and nitroprusside, and brain natriuretic peptide were compared with the α-adrenergic antagonist phentolamine, calcium-channel antagonist verapamil, and hydralazine. Radial artery diameter was measured by high resolution ultrasound, forearm blood flow by strain gauge plethysmography, and pulse wave velocity by pressure recording cuffs placed over the distal brachial and radial arteries. Norepinephrine was used to constrict the radial artery to generate a greater range of vasodilator tone when examining pulse wave velocity. Despite dilating resistance vasculature, phentolamine and verapamil had little effect on radial artery diameter (mean dilation 〈9%). By contrast, for comparable actions on resistance vessels, nitroglycerine and nitroprusside but not brain natriuretic peptide had powerful actions to dilate the radial artery (dilations of 31.3±3.6%, 23.6±3.1%, and 9.8±2.0% for nitroglycerine, nitroprusside, and brain natriuretic peptide, respectively). Changes in pulse wave velocity followed those in arterial diameter irrespective of the signaling pathway used to modulate arterial tone ( R =–0.89, P 〈0.05). Basal tone in human muscular arteries is relatively unaffected by α-adrenergic or calcium-channel blockade, but is functionally or directly antagonized by NO donors. The differential response to NO donors suggests that there is potential to manipulate the downstream pathway to confer greater specificity for large arteries with a resultant decrease in pressure wave reflection and systolic blood pressure.

Beschreibung: Augmentation pressure (AP), the increment in aortic pressure above its first systolic shoulder, is thought to be determined mainly by pressure wave reflection but could be influenced by ventricular ejection characteristics. We sought to determine the mechanism by which AP is selectively reduced by nitroglycerin (NTG). Simultaneous measurements of aortic pressure and flow were made at the time of cardiac catheterization in 30 subjects (11 women; age, 61±13 years [mean±SD]) to perform wave intensity analysis and calculate forward and backward components of AP generated by the ventricle and arterial tree, respectively. Measurements were made at baseline and after NTG given systemically (800 μg sublingually, n=20) and locally by intracoronary infusion (1 μg/min; n=10). Systemic NTG had no significant effect on first shoulder pressure but reduced augmentation (and central pulse pressure) by 12.8±3.1 mm Hg ( P 〈0.0001). This resulted from a reduction in forward and backward wave components of AP by 7.0±2.4 and 5.8±1.3 mm Hg, respectively (each P 〈0.02). NTG had no significant effect on the ratio of amplitudes of either backward/forward waves or backward/forward compression wave energies, suggesting that effects on the backward wave were largely secondary to those on the forward wave. Time to the forward expansion wave was reduced ( P 〈0.05). Intracoronary NTG decreased AP by 8.3±3.6 mm Hg ( P 〈0.05) with no significant effect on the backward wave. NTG reduces AP and central pulse pressure by a mechanism that is, at least in part, independent of arterial reflections and relates to ventricular contraction/relaxation dynamics with enhanced myocardial relaxation.

Beschreibung: On 21 January 2005, a moderate magnetic storm produced a number of anomalous features, some seen more typically during superstorms. The aim of this study is to establish the differences in the space environment from what we expect (and normally observe) for a storm of this intensity that make it behave in some ways like a superstorm. The storm was driven by one of the fastest interplanetary coronal mass ejections in solar cycle 23, containing a piece of the dense erupting solar filament material. The momentum of the massive solar filament caused it to push its way through the flux rope as the ICME decelerated moving toward 1 AU creating the appearance of an eroded flux rope (see companion paper by Manchester et al., J. Geophys. Res., [2014]) and, in this case, limiting the intensity of the resulting geomagnetic storm. On impact, the solar filament further distrupted the partial ring current shielding in existence at the time, creating a brief superfountain in the equatorial ionosphere – an unusual occurrence for a moderate storm. Within one hour after impact, a cold dense plasma sheet (CDPS) formed out of the filament material. As the IMF rotated from obliquely to more purely northward, the magnetotail transformed from an open to a closed configuration and the CDPS evolved from warmer to cooler temperatures. Plasma sheet densities reached tens per cm-3 along the flanks – high enough to inflate the magnetotail in the simulation under northward IMF conditions despite the cool temperatures. Observational evidence for this stretching was provided by a corresponding expansion and intensification of both the auroral oval and ring current precipitation zones linked to magnetotail stretching by field-line curvature scattering. Strong Joule heating in the cusps, a by-product of the CDPS formation process, contributed to an equatorward neutral wind surge that reached low latitudes within 1-2 hours and intensified the equatorial ionization anomaly. Understanding the geospace consequences of extremes in density and pressure is important because some of the largest and most damaging space weather events ever observed contained similar intervals of dense solar material.

Beschreibung: Global, ion equatorial flux distributions and energy spectra are presented from stereoscopic TWINS 1 and TWINS 2 ENA images for two time periods, 29 May 2010, 1330–1430 UT and 26 May 2011, 1645–1715 UT. The first is just after the main phase of a weak (minimum SYM/H ≈ −70 to −80 nT) CIR (Co-rotating Interaction Region) driven geomagnetic storm. The second is during a relatively quiet period. The global ion distributions show multiple spatial peaks that are coincident with peaks in the AE index. The energy spectra have a primary maximum in the 15–20 keV range. Below the energy maximum, the flux is Maxwellian. Above the main maximum, the flux is either significantly below that of a Maxwellian or has a second component with a maximum in the 40–50 keV range. For the 29 May 2010, 1330–1430 UT time period, the flux from the TWINS stereoscopic images is compared to the results from TWINS 1 and TWINS 2 alone illustrating the advantage of stereoscopic viewing. The flux deconvolved from the TWINS images also show spatial and temporal correlations with THEMIS in-situ measurements. Magnetic field dipolarizations observed by GOES support the existence of a peak in the ion flux in the midnight/dawn sector. In summary, increased spatial resolution from TWINS stereoscopic ENA images is demonstrated. Multiple peaks in the ion flux of trapped particles in the ring current are observed. THEMIS ESA in-situ ion flux measurements and GOES geosynchronous magnetic field measurements are consistent with the spatial and temporal structure obtained.

Beschreibung: Neuronal NO synthase (nNOS) regulates blood flow in resistance vasculature at rest and during mental stress. To investigate whether nNOS signaling is dysfunctional in essential hypertension, forearm blood flow responses to mental stress were examined in 88 subjects: 48 with essential hypertension (42±14 years; blood pressure, 141±17/85±15 mm Hg; mean±SD) and 40 normotensive controls (38±14 years; 117±13/74±9 mm Hg). A subsample of 34 subjects (17 hypertensive) participated in a single blind 2-phase crossover study, in which placebo or sildenafil 50 mg PO was administered before an intrabrachial artery infusion of the selective nNOS inhibitor S-methyl- l -thiocitrulline (SMTC, 0.05, 0.1, and 0.2 μmol/min) at rest and during mental stress. In a further subsample (n=21) with an impaired blood flow response to mental stress, responses were measured in the presence and absence of the α-adrenergic antagonist phentolamine. The blood flow response to mental stress was impaired in hypertensive compared with normotensive subjects (37±7% versus 70±8% increase over baseline; P 〈0.001). SMTC blunted responses to mental stress in normotensive but not in hypertensive subjects (reduction of 40±11% versus 3.0±14%, respectively, P =0.01, between groups). Sildenafil reduced the blood flow response to stress in normotensive subjects from 89±14% to 43±14% ( P 〈0.03) but had no significant effect in hypertensive subjects. Phentolamine augmented impaired blood flow responses to mental stress from 39±8% to 67±13% ( P 〈0.02). Essential hypertension is associated with impaired mental stress–induced nNOS-mediated vasodilator responses; this may relate to increased sympathetic outflow in hypertension. nNOS dysfunction may impair vascular homeostasis in essential hypertension and contribute to stress-induced cardiovascular events.

Beschreibung: Pulsatile components of blood pressure may arise from forward (ventricular generated) or backward wave travel in the arterial tree. The objective of this study was to determine the relative contributions of forward and backward waves to pulsatility. We used wave intensity and wave separation analysis to determine pulsatile components of blood pressure during inotropic and vasopressor stimulation by dobutamine and norepinephrine in normotensive subjects and compared pulse pressure components in hypertensive (mean±SD, 48.8±11.3 years; 165±26.6/99±14.2 mm Hg) and normotensive subjects (52.2±12.6 years; 120±14.2/71±8.2 mm Hg). Dobutamine (7.5 μg/kg per minute) increased the forward compression wave generated by the ventricle and increased pulse pressure from 36.8±3.7 to 59.0±3.4 mm Hg (mean±SE) but had no significant effect on mean arterial pressure or the midsystolic backward compression wave. By contrast, norepinephrine (50 ng/kg per minute) had no significant effect on the forward compression wave but increased the midsystolic backward compression wave. Despite this increase in the backward compression wave, and an increase in mean arterial pressure, norepinephrine increased central pulse pressure less than dobutamine (increases of 22.1±3.8 and 7.2±2.8 mm Hg for dobutamine and norepinephrine, respectively; P 〈0.02). An elevated forward wave component (mean±SE, 50.4±3.4 versus 35.2±1.8 mm Hg, in hypertensive and normotensive subjects, respectively; P 〈0.001) accounted for approximately two thirds of the total difference in central pulse pressures between hypertensive and normotensive subjects. Increased central pulse pressure during inotropic stimulation and in essential hypertension results primarily from the forward compression wave.

Beschreibung: Estimation of aortic and left ventricular (LV) pressure usually requires measurements that are difficult to acquire during the imaging required to obtain concurrent LV dimensions essential for determination of LV mechanical properties. We describe a novel method for deriving aortic pressure from the aortic flow velocity. The target pressure waveform is divided into an early systolic upstroke, determined by the water hammer equation, and a diastolic decay equal to that in the peripheral arterial tree, interposed by a late systolic portion described by a second-order polynomial constrained by conditions of continuity and conservation of mean arterial pressure. Pulse wave velocity (PWV, which can be obtained through imaging), mean arterial pressure, diastolic pressure, and diastolic decay are required inputs for the algorithm. The algorithm was tested using 1 ) pressure data derived theoretically from prespecified flow waveforms and properties of the arterial tree using a single-tube 1-D model of the arterial tree, and 2 ) experimental data acquired from a pressure/Doppler flow velocity transducer placed in the ascending aorta in 18 patients (mean ± SD: age 63 ± 11 yr, aortic BP 136 ± 23/73 ± 13 mmHg) at the time of cardiac catheterization. For experimental data, PWV was calculated from measured pressures/flows, and mean and diastolic pressures and diastolic decay were taken from measured pressure (i.e., were assumed to be known). Pressure reconstructed from measured flow agreed well with theoretical pressure: mean ± SD root mean square (RMS) error 0.7 ± 0.1 mmHg. Similarly, for experimental data, pressure reconstructed from measured flow agreed well with measured pressure (mean RMS error 2.4 ± 1.0 mmHg). First systolic shoulder and systolic peak pressures were also accurately rendered (mean ± SD difference 1.4 ± 2.0 mmHg for peak systolic pressure). This is the first noninvasive derivation of aortic pressure based on fluid dynamics (flow and wave speed) in the aorta itself.