Hydralazine administration activates sympathetic preganglionic neurons whose activity mobilizes glucose and increases cardiovascular function

Parker, Lindsay M.; Damanhuri, Hanafi Ahmad; Fletcher, S.; Goodchild, Ann K.

doi:10.1016/j.brainres.2015.01.049

Cited by 3 publications

(5 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In V‐HeFT II (the Vasodilator‐Heart Failure Trial), treatment with ISDN+hydral increased norepinephrine levels . More recently, hydralazine has been shown to activate preganglionic sympathetic neurons . Our findings of increased preload (suggesting volume retention), adverse interstitial remodeling, and reduced 6MW distances may be consistent with sympathetic nervous system activation .…”

Section: Discussionsupporting

confidence: 84%

“…44 More recently, hydralazine has been shown to activate preganglionic sympathetic neurons. 45 Our findings of increased preload (suggesting volume retention), adverse interstitial remodeling, and reduced 6MW distances may be consistent with sympathetic nervous system activation. [46][47][48] Other manifestations of sympathetic activation, such as tachycardia, could have been masked by the high utilization of concomitant cardiovascular medications, such as b-blockers.…”

Section: Discussionsupporting

confidence: 77%

See 1 more Smart Citation

Isosorbide Dinitrate, With or Without Hydralazine, Does Not Reduce Wave Reflections, Left Ventricular Hypertrophy, or Myocardial Fibrosis in Patients With Heart Failure With Preserved Ejection Fraction

Zamani

Akers

Soto‐Calderon

et al. 2017

JAHA

View full text Add to dashboard Cite

BackgroundWave reflections, which are increased in patients with heart failure with preserved ejection fraction, impair diastolic function and promote pathologic myocardial remodeling. Organic nitrates reduce wave reflections acutely, but whether this is sustained chronically or affected by hydralazine coadministration is unknown.Methods and ResultsWe randomized 44 patients with heart failure with preserved ejection fraction in a double‐blinded fashion to isosorbide dinitrate (ISDN; n=13), ISDN+hydralazine (ISDN+hydral; n=15), or placebo (n=16) for 6 months. The primary end point was the change in reflection magnitude (RM; assessed with arterial tonometry and Doppler echocardiography). Secondary end points included change in left ventricular mass and fibrosis, measured with cardiac magnetic resonance imaging, and the 6‐minute walk distance. ISDN reduced aortic characteristic impedance (mean baseline=0.15 [95% CI, 0.14–0.17], 3 months=0.11 [95% CI, 0.10–0.13], 6 months=0.10 [95% CI, 0.08–0.12] mm Hg/mL per second; P=0.003) and forward wave amplitude (Pf, mean baseline=54.8 [95% CI, 47.6–62.0], 3 months=42.2 [95% CI, 33.2–51.3]; 6 months=37.0 [95% CI, 27.2–46.8] mm Hg, P=0.04), but had no effect on RM (P=0.64), left ventricular mass (P=0.33), or fibrosis (P=0.63). ISDN+hydral increased RM (mean baseline=0.39 [95% CI, 0.35–0.43]; 3 months=0.31 [95% CI, 0.25–0.36]; 6 months=0.44 [95% CI, 0.37–0.51], P=0.03), reduced 6‐minute walk distance (mean baseline=343.3 [95% CI, 319.2–367.4]; 6 months=277.0 [95% CI, 242.7–311.4] meters, P=0.022), and increased native myocardial T1 (mean baseline=1016.2 [95% CI, 1002.7–1029.7]; 6 months=1054.5 [95% CI, 1036.5–1072.3], P=0.021). A high proportion of patients experienced adverse events with active therapy (ISDN=61.5%, ISDN+hydral=60.0%; placebo=12.5%; P=0.007).Conclusions ISDN, with or without hydralazine, does not exert beneficial effects on RM, left ventricular remodeling, or submaximal exercise and is poorly tolerated. ISDN+hydral appears to have deleterious effects on RM, myocardial remodeling, and submaximal exercise. Our findings do not support the routine use of these vasodilators in patients with heart failure with preserved ejection fraction.Clinical Trial Registration URL: www.clinicaltrials.gov. Unique identifier: NCT01516346.

show abstract

Section: Discussionsupporting

confidence: 84%

Section: Discussionsupporting

confidence: 77%

Isosorbide Dinitrate, With or Without Hydralazine, Does Not Reduce Wave Reflections, Left Ventricular Hypertrophy, or Myocardial Fibrosis in Patients With Heart Failure With Preserved Ejection Fraction

Zamani

Akers

Soto‐Calderon

et al. 2017

JAHA

View full text Add to dashboard Cite

show abstract

“…="Inflection Point" reg [1,6]="Count of c-Fos-positive neurons" reg [1,7]="Background percentage threshold (%)" reg [2,6]=mod$coefficients[1]/2 reg[2, 7]=-mod$coefficients [2]/mod$coefficients [3] export(reg, file = "Result_Non_Linear_Regression.xlsx", overwrite = TRUE) ## tgc2[,8]=mod$coefficients [1]/(1+exp(-(mod$coefficients [2]+mod$coefficients[3] * x))) colnames(tgc2) [8]="est" # Gr?fico com todos os grupos ggplot(tgc, aes(x=Threshold, y=X, colour=Animals)) + labs(x="Background percentage threshold (%)") + labs(y="Average number of the core count of c-Fos-positive neurons") + geom_errorbar(aes(ymin=X-se, ymax=X+se), colour="black", width=1) + theme_bw() + xlim(min(tgc2$Threshold)-2, max(tgc2$Threshold)+2) + geom_point(aes(shape=Animals),size=3, colour="black") + geom_line(data = tgc2, aes(x = Threshold, y = est), size =1.5, color="red") + geom_segment(aes(x = reg [2,7], y = 0, xend = reg [2,7], yend = reg [2,6]), size=1, colour="red", linetype = "dashed") + geom_segment(aes(x = min(tgc2$Threshold)-2, y = reg [2,6], xend = reg [2,7], yend = reg [2,6]),size = 1, colour="red", linetype = "dashed") ggsave(filename = "Nonlinear Regression Adjustment.tiff", scale = 2:2, dpi = 300)…”

Section: Discussionmentioning

confidence: 99%

“…Other works have used a threshold limit with a fixed value [8,20] to choose which cores have to be counted and which does not. That is a good strategy, but using the same threshold for all immunofluorescence pictures cannot be so efficient because the value of the background usually has a considerable variation, even if camera's diaphragm is kept at the same frequency during the acquisition process.…”

Section: Discussionmentioning

confidence: 99%

“…Immunofluorescence to Fos protein is a widespread procedure used by neuroscientists to study both excitatory [2,3] and inhibitory [4] activations in the neural circuits [2,[5][6][7]. It has been used in qualitative studies to show the activation of the neurons in the central nervous system after a specific stimulus [8,9]. Besides, it has also been used in quantitative studies, in which the number of c-Fos-positive neurons is counted to evaluate the recruitment of the neurons in the neural circuit nuclei.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Increased Accuracy to c-Fos-Positive Neuron Counting

Silva

Quintans

Lucca

2021

BioMed Research International

View full text Add to dashboard Cite

There is not a described method to count the core label of c-Fos-positive neurons, avoiding false-positive and false-negative results. The aim of this manuscript is to provide guidelines for a secure and accurate method to calculate a threshold to select which core of c-Fos-positive neurons marked by immunofluorescence has to be scored. A background percentage was calculated by dividing the intensity value (0 to 255) of the core of c-Fos-positive neurons by its surrounding background from the 8-bit images obtained in a previous study. Using the background percentage from 20% up to 98%, raising 2% once for each score, as threshold to choose which core has to be counted, a script was written for the R program to count the number of the c-Fos-positive neurons and the comparison between control and experimental groups. The differences of the average number of the core counted c-Fos-positive neurons between control and experimental groups, at all thresholds studied, showed a rising value related to an increase of the background percentage threshold as well as a decrease of its p value related to an increase of the threshold of background percentage. For the smallest thresholds (high intensity of label), the differences between groups are suppressed (false negative). However, for the biggest thresholds (nonspecific label), these differences are always the same (false positive). Therefore, to avoid the false-negative and the false-positive values, it was chosen as the threshold of 62% the inflection point of the linear regression, which is equally different from the biggest and smallest values of the differences between groups.

show abstract

Understanding cellular glycan surfaces in the central nervous system

Iqbal

Fard

Everest‐Dass

et al. 2018

Biochemical Society Transactions

View full text Add to dashboard Cite

Glycosylation, the enzymatic process by which glycans are attached to proteins and lipids, is the most abundant and functionally important type of post-translational modification associated with brain development, neurodegenerative disorders, psychopathologies and brain cancers. Glycan structures are diverse and complex; however, they have been detected and targeted in the central nervous system (CNS) by various immunohistochemical detection methods using glycan-binding proteins such as anti-glycan antibodies or lectins and/or characterized with analytical techniques such as chromatography and mass spectrometry. The glycan structures on glycoproteins and glycolipids expressed in neural stem cells play key roles in neural development, biological processes and CNS maintenance, such as cell adhesion, signal transduction, molecular trafficking and differentiation. This brief review will highlight some of the important findings on differential glycan expression across stages of CNS cell differentiation and in pathological disorders and diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis, amyotrophic lateral sclerosis, schizophrenia and brain cancer.

show abstract

Hydralazine administration activates sympathetic preganglionic neurons whose activity mobilizes glucose and increases cardiovascular function

Cited by 3 publications

References 65 publications

Isosorbide Dinitrate, With or Without Hydralazine, Does Not Reduce Wave Reflections, Left Ventricular Hypertrophy, or Myocardial Fibrosis in Patients With Heart Failure With Preserved Ejection Fraction

Isosorbide Dinitrate, With or Without Hydralazine, Does Not Reduce Wave Reflections, Left Ventricular Hypertrophy, or Myocardial Fibrosis in Patients With Heart Failure With Preserved Ejection Fraction

Increased Accuracy to c-Fos-Positive Neuron Counting

Understanding cellular glycan surfaces in the central nervous system

Contact Info

Product

Resources

About