scholarly journals Inhibition of nitric oxide synthase does not alter dynamic cerebral autoregulation in humans

2004 ◽  
Vol 286 (3) ◽  
pp. H863-H869 ◽  
Author(s):  
Rong Zhang ◽  
Thad E. Wilson ◽  
Sarah Witkowski ◽  
Jian Cui ◽  
Craig G. Crandall ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Steady State ◽  
Transfer Function ◽  
Supine Position ◽  
Cerebral Autoregulation ◽  
Low Frequencies ◽  
Phenylephrine Infusion ◽  
Oxide Synthase ◽  
Transfer Function Gain ◽  
Dynamic Cerebral Autoregulation

The aim of this study was to determine whether inhibition of nitric oxide synthase (NOS) alters dynamic cerebral autoregulation in humans. Beat-to-beat blood pressure (BP) and cerebral blood flow (CBF) velocity (transcranial Doppler) were measured in eight healthy subjects in the supine position and during 60° head-up tilt (HUT). NOS was inhibited by intravenous NG-monomethyl-l-arginine (l-NMMA) infusion. Dynamic cerebral autoregulation was quantified by transfer function analysis of beat-to-beat changes in BP and CBF velocity. Pressor effects of l-NMMA on cerebral hemodynamics were compared with those of phenylephrine infusion. In the supine position, l-NMMA increased mean BP from 83 ± 3 to 94 ± 3 mmHg ( P < 0.01). However, CBF velocity remained unchanged. Consequently, cerebrovascular resistance index (CVRI) increased by 15% ( P < 0.05). BP and CBF velocity variability and transfer function gain at the low frequencies of 0.07–0.20 Hz did not change with l-NMMA infusion. Similar changes in mean BP, CBF velocity, and CVRI were observed after phenylephrine infusion, suggesting that increase in CVRI after l-NMMA was mediated myogenically by increase in arterial pressure rather than a direct effect of cerebrovascular NOS inhibition. During baseline tilt without l-NMMA, steady-state BP increased and CBF velocity decreased. BP and CBF velocity variability at low frequencies increased in parallel by 277% and 217%, respectively ( P < 0.05). However, transfer function gain remained unchanged. During tilt with l-NMMA, changes in steady-state hemodynamics and BP and CBF velocity variability as well as transfer gain and phase were similar to those without l-NMMA. These data suggest that inhibition of tonic production of NO does not appear to alter dynamic cerebral autoregulation in humans.

Differential effects of acute hypoxia and high altitude on cerebral blood flow velocity and dynamic cerebral autoregulation: alterations with hyperoxia

2008 ◽  
Vol 104 (2) ◽  
pp. 490-498 ◽  
Author(s):  
Philip N. Ainslie ◽  
Shigehiko Ogoh ◽  
Katie Burgess ◽  
Leo Celi ◽  
Ken McGrattan ◽  
...  
Keyword(s):  
Blood Flow ◽  
Transfer Function ◽  
High Altitude ◽  
Blood Flow Velocity ◽  
Cerebral Autoregulation ◽  
Acute Hypoxia ◽  
Low Frequency ◽  
Frequency Range ◽  
Transfer Function Gain ◽  
Dynamic Cerebral Autoregulation

We hypothesized that 1) acute severe hypoxia, but not hyperoxia, at sea level would impair dynamic cerebral autoregulation (CA); 2) impairment in CA at high altitude (HA) would be partly restored with hyperoxia; and 3) hyperoxia at HA and would have more influence on blood pressure (BP) and less influence on middle cerebral artery blood flow velocity (MCAv). In healthy volunteers, BP and MCAv were measured continuously during normoxia and in acute hypoxia (inspired O2 fraction = 0.12 and 0.10, respectively; n = 10) or hyperoxia (inspired O2 fraction, 1.0; n = 12). Dynamic CA was assessed using transfer-function gain, phase, and coherence between mean BP and MCAv. Arterial blood gases were also obtained. In matched volunteers, the same variables were measured during air breathing and hyperoxia at low altitude (LA; 1,400 m) and after 1–2 days after arrival at HA (∼5,400 m, n = 10). In acute hypoxia and hyperoxia, BP was unchanged whereas it was decreased during hyperoxia at HA (−11 ± 4%; P < 0.05 vs. LA). MCAv was unchanged during acute hypoxia and at HA; however, acute hyperoxia caused MCAv to fall to a greater extent than at HA (−12 ± 3 vs. −5 ± 4%, respectively; P < 0.05). Whereas CA was unchanged in hyperoxia, gain in the low-frequency range was reduced during acute hypoxia, indicating improvement in CA. In contrast, HA was associated with elevations in transfer-function gain in the very low- and low-frequency range, indicating CA impairment; hyperoxia lowered these elevations by ∼50% ( P < 0.05). Findings indicate that hyperoxia at HA can partially improve CA and lower BP, with little effect on MCAv.

scholarly journals Dexmedetomidine Weakens Dynamic Cerebral Autoregulation as Assessed by Transfer Function Analysis and the Thigh Cuff Method

2008 ◽  
Vol 109 (4) ◽  
pp. 642-650 ◽  
Author(s):  
Yojiro Ogawa ◽  
Ken-ichi Iwasaki ◽  
Ken Aoki ◽  
Wakako Kojima ◽  
Jitsu Kato ◽  
...  
Keyword(s):  
Steady State ◽  
Transfer Function ◽  
Arterial Pressure ◽  
Cerebral Autoregulation ◽  
Function Analysis ◽  
Low Frequency ◽  
High Dose ◽  
Frequency Range ◽  
Transfer Function Analysis ◽  
Dynamic Cerebral Autoregulation

Background Dexmedetomidine, which is often used in intensive care units in patients with compromised circulation, might induce further severe decreases in cerebral blood flow (CBF) with temporal decreases in arterial pressure induced by various stimuli if dynamic cerebral autoregulation is not improved. Therefore, the authors hypothesized that dexmedetomidine strengthens dynamic cerebral autoregulation. Methods Fourteen healthy male subjects received placebo, low-dose dexmedetomidine (loading, 3 microg x kg(-1) x h(-1) for 10 min; maintenance, 0.2 microg x kg(-1) x h(-1) for 60 min), and high-dose dexmedetomidine (loading, 6 microg x kg(-1) x h(-1) for 10 min; maintenance, 0.4 microg x kg(-1) x h(-1) for 60 min) infusions in a randomized, double-blind, crossover study. After 70 min of drug administration, dynamic cerebral autoregulation was estimated by transfer function analysis between arterial pressure variability and CBF velocity variability, and the thigh cuff method. Results Compared with placebo, steady state CBF velocity and mean blood pressure significantly decreased during administration of dexmedetomidine. Transfer function gain in the very-low-frequency range increased and phase in the low-frequency range decreased significantly, suggesting alterations in dynamic cerebral autoregulation in lower frequency ranges. Moreover, the dynamic rate of regulation and percentage restoration in CBF velocity significantly decreased when a temporal decrease in arterial pressure was induced by thigh cuff release. Conclusion Contrary to the authors' hypothesis, the current results of two experimental analyses suggest together that dexmedetomidine weakens dynamic cerebral autoregulation and delays restoration in CBF velocity during conditions of decreased steady state CBF velocity. Therefore, dexmedetomidine may lead to further sustained reductions in CBF during temporal decreases in arterial pressure.

Differential effects of mild central hypovolemia with furosemide administration vs. lower body suction on dynamic cerebral autoregulation

2013 ◽  
Vol 114 (2) ◽  
pp. 211-216 ◽  
Author(s):  
Yojiro Ogawa ◽  
Ken Aoki ◽  
Jitsu Kato ◽  
Ken-ichi Iwasaki
Keyword(s):  
Transfer Function ◽  
Cerebral Autoregulation ◽  
Function Analysis ◽  
Venous Pressure ◽  
Lower Body ◽  
Arterial Blood ◽  
Transfer Function Analysis ◽  
Transfer Function Gain ◽  
Furosemide Administration ◽  
Dynamic Cerebral Autoregulation

Diuretic-induced mild hypovolemia with hemoconcentration reportedly improves dynamic cerebral autoregulation, whereas central hypovolemia without hemoconcentration induced by lower body negative pressure (LBNP) has no effect or impairs dynamic cerebral autoregulation. This discrepancy may be explained by different blood properties, by degrees of central hypovolemia, or both. We investigated the effects of equivalent central hypovolemia induced by furosemide administration or LBNP application on dynamic cerebral autoregulation to test our hypothesis that mild central hypovolemia due to furosemide administration enhances dynamic cerebral autoregulation in contrast to LBNP. Seven healthy male subjects received 0.4 mg/kg furosemide and LBNP, with equivalent decreases in central venous pressure (CVP). Dynamic cerebral autoregulation was assessed by spectral and transfer function analysis between beat-to-beat mean arterial blood pressure (MAP) and mean cerebral blood flow velocity (MCBFV). CVP decreased by ∼3–4 mmHg with both furosemide administration (∼26 mg) and LBNP (approximately −20 mmHg). Steady state MCBFV remained unchanged with both techniques, whereas MAP increased significantly with furosemide administration. Coherence and transfer function gain in the low and high frequency ranges with hypovolemia due to furosemide administration were significantly lower than those due to LBNP (ANOVA interaction effects, P < 0.05), although transfer function gain in the very low frequency range did not change. Our results suggest that although the decreases in CVP were equivalent between furosemide administration and LBNP, the resultant central hypovolemia differentially affected dynamic cerebral autoregulation. Mild central hypovolemia with hemoconcentration resulting from furosemide administration may enhance dynamic cerebral autoregulation compared with LBNP.

Cerebral circulation during mild +Gz hypergravity by short-arm human centrifuge

2012 ◽  
Vol 112 (2) ◽  
pp. 266-271 ◽  
Author(s):  
Ken-ichi Iwasaki ◽  
Yojiro Ogawa ◽  
Ken Aoki ◽  
Ryo Yanagida
Keyword(s):  
Steady State ◽  
Transfer Function ◽  
Arterial Pressure ◽  
High Frequency ◽  
Cerebral Circulation ◽  
Cerebral Autoregulation ◽  
Low Frequency ◽  
Frequency Range ◽  
Pressure Oscillations ◽  
Dynamic Cerebral Autoregulation

We examined changes in cerebral circulation in 15 healthy men during exposure to mild +Gz hypergravity (1.5 Gz, head-to-foot) using a short-arm centrifuge. Continuous arterial pressure waveform (tonometry), cerebral blood flow (CBF) velocity in the middle cerebral artery (transcranial Doppler ultrasonography), and partial pressure of end-tidal carbon dioxide (ETco2) were measured in the sitting position (1 Gz) and during 21 min of exposure to mild hypergravity (1.5 Gz). Dynamic cerebral autoregulation was assessed by spectral and transfer function analysis between beat-to-beat mean arterial pressure (MAP) and mean CBF velocity (MCBFV). Steady-state MAP did not change, but MCBFV was significantly reduced with 1.5 Gz (−7%). ETco2 was also reduced (−12%). Variability of MAP increased significantly with 1.5 Gz in low (53%)- and high-frequency ranges (88%), but variability of MCBFV did not change in these frequency ranges, resulting in significant decreases in transfer function gain between MAP and MCBFV (gain in low-frequency range, −17%; gain in high-frequency range, −13%). In contrast, all of these indexes in the very low-frequency range were unchanged. Transfer from arterial pressure oscillations to CBF fluctuations was thus suppressed in low- and high-frequency ranges. These results suggest that steady-state global CBF was reduced, but dynamic cerebral autoregulation in low- and high-frequency ranges was improved with stabilization of CBF fluctuations despite increases in arterial pressure oscillations during mild +Gz hypergravity. We speculate that this improvement in dynamic cerebral autoregulation within these frequency ranges may have been due to compensatory effects against the reduction in steady-state global CBF.

Effect of inhibition of nitric oxide synthase on dynamic cerebral autoregulation in humans

2000 ◽  
Vol 99 (6) ◽  
pp. 555-560 ◽  
Author(s):  
R. P. WHITE ◽  
P. VALLANCE ◽  
H. S. MARKUS
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Blood Flow ◽  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Cerebral Autoregulation ◽  
Arterial Blood ◽  
The Mean ◽  
Oxide Synthase ◽  
Dynamic Cerebral Autoregulation

Cerebral blood flow is maintained constant over a range of cerebral perfusion pressures by cerebral autoregulation. Impaired cerebral autoregulation may be important in the pathogenesis of cerebral ischaemia. The mechanisms mediating normal cerebral autoregulation in humans are poorly understood. We used a recently described transcranial Doppler technique, which allows non-invasive measurement of dynamic cerebral autoregulation, to test the hypothesis that nitric oxide mediates cerebral autoregulation. The rate of rise of middle cerebral artery blood flow velocity, compared with that of arterial blood pressure, was determined following a stepwise fall in arterial blood pressure, in order to calculate an autoregulatory index. The effect of the nitric oxide synthase inhibitor NG-monomethyl-L-arginine (L-NMMA) on dynamic autoregulation was compared with that of noradrenaline titrated to result in a similar rise in blood pressure. Six healthy subjects were studied in each group. The mean (S.D.) change in autoregulatory index following noradrenaline at a similar pressor dose was significantly greater than the change following the L-NMMA bolus: 1.1 (1.2) compared with -0.8 (0.8) for the left middle cerebral artery (P = 0.002), and 1.1 (0.8) compared with -0.8 (0.8) for the right middle cerebral artery (P = 0.002). There was no difference in the mean (S.D.) blood pressure increase resulting from the two agents: L-NMMA, 19.7 (7.4) mmHg; noradrenaline, 15.5 (4.8) mmHg (P = 0.281). These results suggest that nitric oxide mediates at least part of the dynamic phase of cerebral autoregulation in humans. Reduced nitric oxide release may play a role in the impaired cerebral autoregulation seen in patients with, or at risk of, cerebral ischaemia.

scholarly journals Dynamic cerebral autoregulation during repeated squat-stand maneuvers

2009 ◽  
Vol 106 (1) ◽  
pp. 153-160 ◽  
Author(s):  
Jurgen A. H. R. Claassen ◽  
Benjamin D. Levine ◽  
Rong Zhang
Keyword(s):  
Transfer Function ◽  
Cerebral Autoregulation ◽  
Function Analysis ◽  
Low Frequency ◽  
Low Frequencies ◽  
Pass Filter ◽  
Postural Changes ◽  
Transfer Function Analysis ◽  
Spontaneous Oscillations ◽  
Dynamic Cerebral Autoregulation

Transfer function analysis of spontaneous oscillations in blood pressure (BP) and cerebral blood flow (CBF) can quantify the dynamic relationship between BP and CBF. However, such oscillation amplitudes are often small and of questionable clinical significance, vary substantially, and cannot be controlled. At the very low frequencies (<0.07 Hz), coherence between BP and CBF often is low (<0.50) and their causal relationship is debated. Eight healthy subjects performed repeated squat-stand maneuvers to induce large oscillations in BP at frequencies of 0.025 and 0.05 Hz (very low frequency) and 0.1 Hz (low frequency), respectively. BP (Finapres), CBF velocity (CBFV; transcranial Doppler), and end-tidal CO2 (capnography) were monitored. Spectral analysis was used to quantify oscillations in BP and CBFV and to estimate transfer function phase, gain, and coherence. Compared with spontaneous oscillations, induced oscillations had higher coherence [mean 0.8 (SD 0.11); >0.5 in all subjects at all frequencies] and lower variability in phase estimates. However, gain estimates remained unchanged. Under both conditions, the “high-pass filter” characteristics of dynamic autoregulation were observed. In conclusion, using repeated squat-stand maneuvers, we were able to study dynamic cerebral autoregulation in the low frequencies under conditions of hemodynamically strong and causally related oscillations in BP and CBFV. This not only enhances the confidence of transfer function analysis as indicated by high coherence and improved phase estimation but also strengthens the clinical relevance of this method as induced oscillations in BP and CBFV mimic those associated with postural changes in daily life.

Dynamic cerebral autoregulation after bed rest: effects of volume loading and exercise countermeasures

2014 ◽  
Vol 116 (1) ◽  
pp. 24-31 ◽  
Author(s):  
Sung-Moon Jeong ◽  
Gyu-Sam Hwang ◽  
Seon-Ok Kim ◽  
Benjamin D. Levine ◽  
Rong Zhang
Keyword(s):  
Transfer Function ◽  
Plasma Volume ◽  
Cerebral Autoregulation ◽  
Bed Rest ◽  
Exercise Group ◽  
Volume Loading ◽  
Sedentary Group ◽  
Transfer Function Gain ◽  
Exercise Countermeasures ◽  
Dynamic Cerebral Autoregulation

This study assessed effects of head-down-tilt (HDT) bed rest on dynamic cerebral autoregulation (CA) in 21 healthy young adults with volume loading and exercise countermeasures. Of these, seven underwent an 18-day bed rest without exercise countermeasures ( sedentary group). Volume loading with dextran infusion was performed after bed rest to restore reduced plasma volume to levels before bed rest. In the other 14 subjects, supine cycling during bed rest was performed to preserve cardiac work from before bed rest ( exercise group). Volume loading was also performed in a subgroup of these subjects ( Ex+Dex, n = 7). Dynamic CA was estimated by transfer function analysis of changes in arterial pressure and cerebral blood flow (CBF) velocity in the very low (VLF, 0.02–0.07 Hz), low (LF, 0.07–0.20 Hz), and high frequency ranges (HF, 0.20–0.35 Hz). After bed rest, transfer function gain was reduced in the sedentary group (VLF, 0.93 ± 0.23 to 0.61 ± 0.23 cm−1·s−1·mmHg; P = 0.007) and in the exercise group (LF, 1.22 ± 0.43 to 0.94 ± 0.26 cm−1·s−1·mmHg; P = 0.005, HF, 1.32 ± 0.55 to 1.00 ± 0.32 cm−1·s−1·mmHg; P = 0.010). After volume loading, transfer function gain increased in the sedentary group but not in the Ex+Dex group. Taken together, these findings suggest that dynamic CA was preserved or improved after HDT bed rest in both sedentary and exercise subjects. Furthermore, increases of transfer function gain with volume loading suggest that changes in plasma volume may play an important role in CBF regulation.

Plasma brain-derived neurotrophic factor and dynamic cerebral autoregulation in acute response to glycemic control following breakfast in young men

2021 ◽  
Vol 320 (1) ◽  
pp. R69-R79
Author(s):  
Hayato Tsukamoto ◽  
Aya Ishibashi ◽  
Christopher J. Marley ◽  
Yasushi Shinohara ◽  
Soichi Ando ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Glycemic Control ◽  
Transfer Function ◽  
Arterial Pressure ◽  
Neurotrophic Factor ◽  
Cerebral Autoregulation ◽  
Brain Derived Neurotrophic Factor ◽  
Postprandial Blood Glucose ◽  
Breakfast Consumption ◽  
Dynamic Cerebral Autoregulation

We examined the acute impact of both low- and high-glycemic index (GI) breakfasts on plasma brain-derived neurotrophic factor (BDNF) and dynamic cerebral autoregulation (dCA) compared with breakfast omission. Ten healthy men (age 24 ± 1 yr) performed three trials in a randomized crossover order; omission and Low-GI (GI = 40) and High-GI (GI = 71) breakfast conditions. Middle cerebral artery velocity (transcranial Doppler ultrasonography) and arterial pressure (finger photoplethysmography) were continuously measured for 5 min before and 120 min following breakfast consumption to determine dCA using transfer function analysis. After these measurements of dCA, venous blood samples for the assessment of plasma BDNF were obtained. Moreover, blood glucose was measured before breakfast and every 30 min thereafter. The area under the curve of 2 h postprandial blood glucose in the High-GI trial was higher than the Low-GI trial ( P < 0.01). The GI of the breakfast did not affect BDNF. In addition, both very-low (VLF) and low-frequency (LF) transfer function phase or gains were not changed during the omission trial. In contrast, LF gain (High-GI P < 0.05) and normalized gain (Low-GI P < 0.05) were decreased by both GI trials, while a decrease in VLF phase was observed in only the High-GI trial ( P < 0.05). These findings indicate that breakfast consumption augmented dCA in the LF range but High-GI breakfast attenuated cerebral blood flow regulation against slow change (i.e., the VLF range) in arterial pressure. Thus we propose that breakfast and glycemic control may be an important strategy to optimize cerebrovascular health.

Dietary salt enhances glomerular endothelial nitric oxide synthase through TGF-β1

1998 ◽  
Vol 275 (1) ◽  
pp. F18-F24 ◽  
Author(s):  
Wei-Zhong Ying ◽  
Paul W. Sanders
Keyword(s):  
Nitric Oxide ◽  
Steady State ◽  
Nitric Oxide Synthase ◽  
Endothelial Nitric Oxide Synthase ◽  
Transforming Growth Factor ◽  
No Production ◽  
Dietary Salt ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide ◽  
Tgf Β1

Dietary salt controls production of nitric oxide (NO), a potent paracrine relaxation factor involved in glomerular filtration and salt excretion. We hypothesized that glomerular NO production was enhanced through endothelial nitric oxide synthase (NOS3). Rats in metabolic cages were studied after 4 days on 0.3% (Lo-salt) or 8.0% (Hi-salt) NaCl diet. Steady-state mRNA and protein levels of NOS3 and calcium-dependent NO production of isolated glomeruli from Hi-salt animals were greater than those values observed in glomeruli from Lo-salt rats. Because dietary salt enhanced glomerular production of transforming growth factor-β1 (TGF-β1) [W.-Z. Ying and P. W. Sanders. Am. J. Physiol. 274 ( Renal Physiol. 43): F635–F641, 1998], studies were then conducted to examine the interaction between NOS3 and TGF-β1. Glomerular steady-state levels of mRNA of NOS3 and TGF-β1 directly correlated ( r 2 = 0.946; P < 0.0001). A neutralizing antibody to TGF-β reduced NOS3 protein and NO production in cultured glomeruli from Hi-salt animals to levels seen in the Lo-salt glomeruli. Thus dietary salt increased glomerular expression of TGF-β1, which in turn augmented NO production through NOS3.

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