scholarly journals Dietary nitrate supplementation reduces low frequency blood pressure fluctuations in rats following distal middle cerebral artery occlusion

2018 ◽  
Vol 125 (3) ◽  
pp. 862-869 ◽  
Author(s):  
Philip D. Allan ◽  
Yu-Chieh Tzeng ◽  
Emma K. Gowing ◽  
Andrew N. Clarkson ◽  
Jui-Lin Fan

It is known that high blood pressure variability (BPV) in acute ischemic stroke is associated with adverse outcomes, yet there are no therapeutic treatments to reduce BPV. Studies have found increasing nitric oxide (NO) bioavailability improves neurological function following stroke, but whether dietary nitrate supplementation could reduce BPV remains unknown. We investigated the effects of dietary nitrate supplementation on heart rate (HR), blood pressure (BP), and beat-to-beat BPV using wireless telemetry in a rat model of distal middle cerebral artery occlusion. Blood pressure variability was characterized by spectral power analysis in the low frequency (LF; 0.2–0.6 Hz) range prestroke and during the 7 days poststroke in a control group ( n = 8) and a treatment group ( n = 8, 183 mg/l sodium nitrate in drinking water). Dietary nitrate supplementation moderately reduced systolic BPV in the LF range by ~11% compared with the control group ( P = 0.03), while resting BP and HR were not different between the two groups ( P = 0.28 and 0.33, respectively). Despite systolic BPV being reduced with dietary nitrate, we found no difference in infarct volumes between the treatment and the control groups (1.59 vs. 1.62 mm3, P = 0.86). These findings indicate that dietary nitrate supplementation is effective in reducing systolic BPV following stroke without affecting absolute BP. In light of mounting evidence linking increased BPV with poor stroke patient outcome, our data support the role of dietary nitrate as an adjunct treatment following ischemic stroke. NEW & NOTEWORTHY Using a rat model of stroke, we found that dietary nitrate supplementation reduced low frequency blood pressure fluctuations following stroke without affecting absolute blood pressure values. Since blood pressure fluctuations are associated with poor clinical outcome in stroke patients, our findings indicate that dietary nitrate could be an effective strategy for reducing blood pressure fluctuations, which could help reduce stroke severity and improve patient recovery.

2008 ◽  
Vol 295 (3) ◽  
pp. H1150-H1155 ◽  
Author(s):  
François Cottin ◽  
Claire Médigue ◽  
Yves Papelier

The aim of the study was to assess the instantaneous spectral components of heart rate variability (HRV) and systolic blood pressure variability (SBPV) and determine the low-frequency (LF) and high-frequency baroreflex sensitivity (HF-BRS) during a graded maximal exercise test. The first hypothesis was that the hyperpnea elicited by heavy exercise could entail a significant increase in HF-SBPV by mechanical effect once the first and second ventilatory thresholds (VTs) were exceeded. It was secondly hypothesized that vagal tone progressively withdrawing with increasing load, HF-BRS could decrease during the exercise test. Fifteen well-trained subjects participated in this study. Electrocardiogram (ECG), blood pressure, and gas exchanges were recorded during a cycloergometer test. Ventilatory equivalents were computed from gas exchange parameters to assess VTs. Spectral analysis was applied on cardiovascular series to compute RR and systolic blood pressure power spectral densities, cross-spectral coherence, gain, and α index of BRS. Three exercise intensity stages were compared: below (A1), between (A2), and above (A3) VTs. From A1 to A3, both HF-SBPV (A1: 45 ± 6, A2: 65 ± 10, and A3: 120 ± 23 mm2Hg, P < 0.001) and HF-HRV increased (A1: 20 ± 5, A2: 23 ± 8, and A3:40 ± 11 ms2, P < 0.02), maintaining HF-BRS (gain, A1: 0.68 ± 0.12, A2: 0.63 ± 0.08, and A3: 0.57 ± 0.09; α index, A1: 0.58 ± 0.08, A2: 0.48 ± 0.06, and A3: 0.50 ± 0.09 ms/mmHg, not significant). However, LF-BRS decreased (gain, A1: 0.39 ± 0.06, A2: 0.17 ± 0.02, and A3: 0.11 ± 0.01, P < 0.001; α index, A1: 0.46 ± 0.07, A2: 0.20 ± 0.02, and A3: 0.14 ± 0.01 ms/mmHg, P < 0.001). As expected, once VTs were exceeded, hyperpnea induced a marked increase in both HF-HRV and HF-SBPV. However, this concomitant increase allowed the maintenance of HF-BRS, presumably by a mechanoelectric feedback mechanism.


2017 ◽  
Vol 313 (1) ◽  
pp. H59-H65 ◽  
Author(s):  
Karambir Notay ◽  
Anthony V. Incognito ◽  
Philip J. Millar

Acute dietary nitrate ([Formula: see text]) supplementation reduces resting blood pressure in healthy normotensives. This response has been attributed to increased nitric oxide bioavailability and peripheral vasodilation, although nitric oxide also tonically inhibits central sympathetic outflow. We hypothesized that acute dietary [Formula: see text] supplementation using beetroot (BR) juice would reduce blood pressure and muscle sympathetic nerve activity (MSNA) at rest and during exercise. Fourteen participants (7 men and 7 women, age: 25 ± 10 yr) underwent blood pressure and MSNA measurements before and after (165–180 min) ingestion of 70ml high-[Formula: see text] (~6.4 mmol [Formula: see text]) BR or [Formula: see text]-depleted BR placebo (PL; ~0.0055 mmol [Formula: see text]) in a double-blind, randomized, crossover design. Blood pressure and MSNA were also collected during 2 min of static handgrip (30% maximal voluntary contraction). The changes in resting MSNA burst frequency (−3 ± 5 vs. 3 ± 4 bursts/min, P = 0.001) and burst incidence (−4 ± 7 vs. 4 ± 5 bursts/100 heart beats, P = 0.002) were lower after BR versus PL, whereas systolic blood pressure (−1 ± 5 vs. 2 ± 5 mmHg, P = 0.30) and diastolic blood pressure (4 ± 5 vs. 5 ± 7 mmHg, P = 0.68) as well as spontaneous arterial sympathetic baroreflex sensitivity ( P = 0.95) were not different. During static handgrip, the change in MSNA burst incidence (1 ± 8 vs. 8 ± 9 bursts/100 heart beats, P = 0.04) was lower after BR versus PL, whereas MSNA burst frequency (6 ± 6 vs. 11 ± 10 bursts/min, P = 0.11) as well as systolic blood pressure (11 ± 7 vs. 12 ± 8 mmHg, P = 0.94) and diastolic blood pressure (11 ± 4 vs. 11 ± 4 mmHg, P = 0.60) were not different. Collectively, these data provide proof of principle that acute BR supplementation can decrease central sympathetic outflow at rest and during exercise. Dietary [Formula: see text] supplementation may represent a novel intervention to target exaggerated sympathetic outflow in clinical populations. NEW & NOTEWORTHY The hemodynamic benefits of dietary nitrate supplementation have been attributed to nitric oxide-mediated peripheral vasodilation. Here, we provide proof of concept that acute dietary nitrate supplementation using beetroot juice can decrease muscle sympathetic outflow at rest and during exercise in a normotensive population. These results have applications for targeting central sympathetic overactivation in disease.


Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Daniel von Bornstädt ◽  
Jessica Seidel ◽  
Mathias Bernard Houben ◽  
Ergin Dilekoz ◽  
Tao Qin ◽  
...  

Background: Peri-infarct depolarizations (PIDs) worsen the outcome of ischemic stroke. Unlike their impact on metabolism and perfusion, triggering factors are virtually unknown. We hypothesized that transient worsening of O2 supply-demand mismatch precipitates a PID in critically hypoperfused penumbra. Methods: We optically imaged cortical blood flow and oxygenation during distal middle cerebral artery occlusion in mice under full systemic physiological monitoring, and tested whether a transient (5 min) drop in O2 supply (hypotension or hypoxia) or increase in O2 demand (somatosensory cortical activation) can trigger PIDs during acute focal cerebral ischemia. Results: Transient hypotension (<70 mmHg) or hypoxia (<90 mmHg) triggered a PID 90% of the time (p<0.01). Increasing the O2 demand by functional activation (tactile stimulation) of moderately ischemic cortex (contralesional forepaw or shoulder S1) increased the 5-min incidence of PIDs by approximately five-fold (p=0.001). Cortical oxyhemoglobin levels dropped by 35-40% in the activated S1 immediately before a PID (p=0.004) confirming increased O2 demand. Cortical foci from which PIDs originated during tactile stimulation had 27-32% residual CBF, indicating the presence of a critical range of ischemia vulnerable to PID initiation upon increased demand. Consistently, activation of non-ischemic cortex (hindpaw S1) or severely ischemic cortex (whisker S1) did not significantly increase the PID rate. Both tetrodotoxin (1 μM topical) and normobaric hyperoxia prevented somatosensory triggering of PIDs. Conclusion: PIDs are triggered upon O2 supply-demand mismatch transients in metastable peri-infarct hot zones due to increased demand or reduced supply. We propose that minimizing sensory stimulation and hypoxic or hypotensive transients in the early stages of stroke and brain injury would reduce PID incidence and their adverse impact on outcome.


Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Kátia B Scapini ◽  
Valéria C Hong ◽  
Janaína B Ferreira ◽  
Sílvia B Souza ◽  
Naomi V Ferreira ◽  
...  

Background: Patients with end-stage renal disease (ESRD) undergoing hemodialysis are susceptible to the development of autonomic dysfunction, which is associated with an increased risk of sudden death. Experimental and clinical evidence suggest a crucial role of autonomic dysfunction for both, the progression of renal disease and for the high rate of cardiovascular events in these patients. In the present study, we evaluated the heart rate variability (HRV), the blood pressure variability (BPV) and the baroreflex sensitivity (BRS) in ESRD patients undergoing hemodialysis and normal controls. Methods: Nine ESRD patients undergoing hemodialysis (mean age 53.4±10.2 years, 4 male) and nine age-matched healthy controls (mean age 52.8±10.2 years, 4 male) were assessed. Non−invasive curves of blood pressure (BP) were recorded continuously (Finometer ®) for 10 minutes, at rest, in the supine position. The heart rate variability (HRV) and systolic blood pressure variability (BPV) were estimated in the time and frequency domain (spectral analysis). The BRS was quantified by alpha index. Statistical analyzes were performed by Student's t test and the results were expressed as mean ± standard deviation. Results: ESRD patients presented lower HRV in time domain than healthy controls (SDNN: 25.8±10.7 vs. 44.6±11.7 ms, p<0.01; VAR NN: 768.3±607.4 vs. 2113.9±1261.6 ms 2 , p=0.01). All frequency domain analyzed indexes, i.e., total power (361.9±297.0 vs. 1227.2±696.3 ms 2 , p<0.01), high-frequency (181.8±128.7 vs. 358.7±179.8 ms 2 , p=0.047), low-frequency (55.1±44.2 vs. 444.6±389.9 ms 2 , p=0.02) and very-low-frequency (72.5±75.1 vs. 279.2±119.5 ms 2 , p<0.01) of HRV were lower in ESRD patients. The BPV was higher in ESRD patients when compared to controls (VAR PAS: 98.4±72.0 vs. 35.4±21.4 ms 2 , p=0.03) and BRS was lower in ESRD patients (alpha index: 4.34±3.05 vs. 7.56±2.50 ms/mmHg, p<0.02). Conclusion: ESRD patients undergoing hemodialysis presents reduced HRV, increase in BPV and reduced baroreflex sensitivity. These impairments may be associated with mortality in ESRD.


Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
George Wong ◽  

Background and purpose: Disability is common after severe stroke resulting from major cerebral artery occlusion despite adoption of prophylactic decompressive craniectomy. Experimental mesenchymal stem cell treatments are commonly administrated through systemic infusion, with limitations in dosage. In this study, the neuro-modulation effect of topical mesenchymal stem cells (MSCs) was tested in a rodent middle carotid artery occlusion (MCAO) model. Methods: Twenty-four hours after MCAO, craniotomy was made and 0.8 x 10 6 GFP-MSCs were topically applied to the ipsilateral parietal cortex (N=30). In the control group, saline were topically applied to the ipsilateral parietal cortex (N=30). Results: After topical MSC treatment, neurological assessments with Rotarod test (at days 3, 7, and 10) and Morris Water Maze test (at days 3, 7, and 14) were significantly better, as compared to the control group; the infarct volume was also smaller. MSCs were found in the penumbra of the infarct 3 days after topical application. In the PCR array analysis of the RNA extracted from penumbra cortex, topical application of MSCs changed 10 gene expressions in the penumbra at day 3 (fold change >1.25, p<0.05 after Bonferroni corrections for multiple comparisons). The seven up-regulated genes (Apoe, Ascl1, Efnb1, Mef2c,Nog,S100a6, B2m) involve neuronal migration, neuronal differentiation, neuronal cell fate determination, regulation of synaptic plasticity, axonogensis;, growth factors, and cell adhesion. Pax2, Pax3 and Th were downregulated. Pax2 and Pax3 are related to apoptosis. Both Apoe and Thl involve synaptic transmission. Conclusions: Topically applied MSCs reduced cerebral infarction volume and improved the neurological function from cerebral ischemia resulting from a major cerebral artery occlusion in a rodent experimental model.


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