Renal Denervation and Celiac Ganglionectomy Decrease Mean Arterial Pressure Similarly in Genetically Hypertensive Schlager (BPH/2J) Mice

Asirvatham‐Jeyaraj, Ninitha; Gauthier, Madeline; Banek, Christopher T.; Ramesh, Abhismitha; Garver, Hannah; Fink, Gregory D.; Osborn, John W.

doi:10.1161/hypertensionaha.119.14069

Cited by 18 publications

(23 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The precise mechanisms underlying the effects of EDN are not well understood; changes in sympathetic activity, lipid metabolism, or hepatic glycogen metabolism are possible mechanisms of action (10,22,29). Further studies to unravel the mechanisms underlying the effect of EDN on hepatocyte function, b-cell function, adipose tissue metabolism, inflammation, and sympathetic activity are eagerly awaited (30).…”

Section: Discussionmentioning

confidence: 99%

Endovascular Celiac Denervation for Glycemic Control in Patients with Type 2 Diabetes Mellitus

Wei

Wang

et al. 2021

Journal of Vascular and Interventional Radiology

View full text Add to dashboard Cite

Purpose: To investigate the safety and efficacy of catheter-based endovascular denervation (EDN) at the celiac artery and abdominal aorta around the celiac artery on glycemic control in patients with type 2 diabetes mellitus (T2DM).Materials and Methods: With a novel catheter system, EDN was conducted at the celiac artery along with the abdominal aorta around the celiac artery in patients with T2DM whose glycosylated hemoglobin (HbA1c) level was >7.5%. The primary outcome was HbA1c level at 6 months. Other outcomes included safety, oral glucose tolerance test, homeostasis model assessment of insulin resistance (HOMA-IR), fasting plasma glucose (FPG) level, 2-hour postprandial plasma glucose (2hPG) level, and C-peptide test.Results: A total of 11 subjects were included for analysis. The technical success was 100%, and no severe treatment-related adverse events or major complications were observed. Both HbA1c level and HOMA-IR were significantly reduced at 6 months (9.9% vs 8.0%, P ¼ .005; 13.3 vs 6.0, P ¼ .016). Decreases in FPG and 2hPG levels were observed (227.2 vs 181.8 mg/dL, P < .001; 322.2 vs 205.2 mg/dL, P ¼ .001). The C-peptide test indicated improved b-cell function (area under the curve, 0.23 vs 0.28 pmol/mL, P ¼ .046). A reduction of daily insulin injection (P ¼ .02) and improvement of liver function (alanine aminotransferase, P ¼ .014; g-glutamyl transpeptidase, P ¼ .021) were also observed.Conclusions: EDN in the celiac artery and abdominal aorta around the celiac artery elicited a clinically significant improvement in glycemic control and insulin resistance in patients with T2DM, with good tolerability as demonstrated by 6-month follow-up. ABBREVIATIONSEDN ¼ endovascular denervation, FPG ¼ fasting plasma glucose, HbA1c ¼ glycosylated hemoglobin, HOMA-IR ¼ homeostasis model assessment of insulin resistance, IQR ¼ interquartile range, NAFLD ¼ nonalcoholic fatty liver disease, OGTT ¼ oral glucose tolerance test, RDN ¼ renal denervation, T2DM ¼ type 2 diabetes mellitus, 2hPG ¼ 2-hour postprandial plasma glucose

show abstract

Section: Discussionmentioning

confidence: 99%

Endovascular Celiac Denervation for Glycemic Control in Patients with Type 2 Diabetes Mellitus

Wei

Wang

et al. 2021

Journal of Vascular and Interventional Radiology

View full text Add to dashboard Cite

show abstract

“…Rats were anesthetized with ketamine/xylazine and prepared accordingly one of the following experimental groups: 1) CB-X: Animals were subjected to bilateral ablation of the carotid bodies; 2) SPL-X: Animals were subjected to splanchnic denervation through celiac ganglionectomy as previously reported in the literature (Asirvatham-Jeyaraj et al, 2021; Li et al, 2010). Briefly, after a midline laparotomy, the visceral organs were gently retracted, and the celiac ganglion was localized and surgically removed using blunt forceps.…”

Section: Methodsmentioning

confidence: 99%

The Carotid Body Detects Circulating Tumor Necrosis Factor-Alpha to Activate a Sympathetic Anti-Inflammatory Reflex

Katayama

Leirão

Kanashiro

et al. 2021

Preprint

View full text Add to dashboard Cite

Recent evidence has suggested that the carotid bodies might act as immunological sensors, detecting pro-inflammatory mediators and signalling to the central nervous system, which, in turn, orchestrates autonomic responses. Here, we demonstrated that the TNF-α receptor type I is expressed in the carotid bodies of rats. The systemic administration of TNF-α increased carotid body afferent discharge and activated glutamatergic neurons in the nucleus tractus solitarius (NTS) that project to the rostral ventrolateral medulla (RVLM), where the majority of pre-sympathetic neurons reside. The activation of these neurons was accompanied by generalized activation of the sympathetic nervous system. Carotid body ablation blunted the TNF-α-induced activation of RVLM-projecting NTS neurons and the increase in splanchnic sympathetic nerve activity. Finally, plasma and spleen levels of cytokines after TNF-α administration were higher in rats subjected to either carotid body ablation or splanchnic sympathetic denervation. Collectively, our findings indicate that the carotid body detects circulating TNF-α to activate a counteracting sympathetic anti-inflammatory mechanism.

show abstract

“…Sixteen-week-old male GC-A WT/WT and GC-A 8E/8E mice were implanted with Data Science International Inc. (St. Paul, MN, USA) transmitters (model HD-X11) for continuous monitoring of arterial pressure and heart rate as previously described. 49 The surgical area was shaved and disinfected with iodine and cleaned with 70% isopropyl alcohol. The mice were placed on a heated surgical pad and a midline back incision was made to subcutaneously implant the body of the transmitter and a second incision was made in the interior side of the left leg to access the femoral artery for placement of the catheter of the transmitter.…”

Section: Telemetry Implantationmentioning

confidence: 99%

Guanylyl cyclase‐A phosphorylation decreases cardiac hypertrophy and improves systolic function in male, but not female, mice

et al. 2021

Self Cite

View full text Add to dashboard Cite

Atrial natriuretic peptide (NP) and BNP increase cGMP, which reduces blood pressure and cardiac hypertrophy by activating guanylyl cyclase (GC)‐A, also known as NPR‐A or Npr1. Although GC‐A is highly phosphorylated, and dephosphorylation inactivates the enzyme, the significance of GC‐A phosphorylation to heart structure and function remains unknown. To identify in vivo processes that are regulated by GC‐A phosphorylation, we substituted glutamates for known phosphorylation sites to make GC‐A8E/8E mice that express an enzyme that cannot be inactivated by dephosphorylation. GC‐A activity, but not protein, was increased in heart and kidney membranes from GC‐A8E/8E mice. Activities were threefold higher in female compared to male cardiac ventricles. Plasma cGMP and testosterone were elevated in male and female GC‐A8E/8E mice, but aldosterone was only increased in mutant male mice. Plasma and urinary creatinine concentrations were decreased and increased, respectively, but blood pressure and heart rate were unchanged in male GC‐A8E/8E mice. Heart weight to body weight ratios for GC‐A8E/8E male, but not female, mice were 12% lower with a 14% reduction in cardiomyocyte cross‐sectional area. Subcutaneous injection of fsANP, a long‐lived ANP analog, increased plasma cGMP and decreased aldosterone in male GC‐AWT/WT and GC‐A8E/8E mice at 15 min, but only GC‐A8E/8E mice had elevated levels of plasma cGMP and aldosterone at 60 min. fsANP reduced ventricular ERK1/2 phosphorylation to a greater extent and for a longer time in the male mutant compared to WT mice. Finally, ejection fractions were increased in male but not female hearts from GC‐A8E/8E mice. We conclude that increased phosphorylation‐dependent GC‐A activity decreases cardiac ERK activity, which results in smaller male hearts with improved systolic function.

show abstract

Renal Denervation and Celiac Ganglionectomy Decrease Mean Arterial Pressure Similarly in Genetically Hypertensive Schlager (BPH/2J) Mice

Cited by 18 publications

References 38 publications

Endovascular Celiac Denervation for Glycemic Control in Patients with Type 2 Diabetes Mellitus

Endovascular Celiac Denervation for Glycemic Control in Patients with Type 2 Diabetes Mellitus

The Carotid Body Detects Circulating Tumor Necrosis Factor-Alpha to Activate a Sympathetic Anti-Inflammatory Reflex

Guanylyl cyclase‐A phosphorylation decreases cardiac hypertrophy and improves systolic function in male, but not female, mice

Contact Info

Product

Resources

About