The organum vasculosum of the lamina terminalis contributes to neurohumoral mechanisms of renal vascular hypertension.

The organum vasculosum of the lamina terminalis (OVLT) is a forebrain circumventricular organ that modulates central autonomic control of arterial pressure and body fluid homeostasis. It has been implicated in the pathogenesis of rat models of hypertension that are driven by increased salt intake since OVLT lesion (OVLTx) attenuates both the DOCA-salt and angiotensin II-salt models. However, its contribution to the development of hypertension that is not salt-dependent, such as the 2 kidney, 1 clip (2K1C) renovascular model, is not clear.

Complex Hemodynamic Responses to Trans-Vascular Electrical Stimulation of the Renal Nerve in Anesthetized Pigs.

The objective of this study was to characterize hemodynamic changes during trans-vascular stimulation of the renal nerve and their dependence on stimulation parameters. We employed a stimulation catheter inserted in the right renal artery under fluoroscopic guidance, in pigs. Systolic, diastolic and pulse blood pressure and heart rate were recorded during stimulations delivered at different intravascular sites along the renal artery or while varying stimulation parameters (amplitude, frequency, and pulse width).

Renal nerves in physiology, pathophysiology and interoception.

Sympathetic efferent renal nerves have key roles in the regulation of kidney function and blood pressure. Increased renal sympathetic nerve activity is thought to contribute to hypertension by promoting renal sodium retention, renin release and renal vasoconstriction. This hypothesis led to the development of catheter-based renal denervation (RDN) for the treatment of hypertension.

Renal interoception in health and disease.

Catheter based renal denervation has recently been FDA approved for the treatment of hypertension. Traditionally, the anti-hypertensive effects of renal denervation have been attributed to the ablation of the efferent sympathetic renal nerves. In recent years the role of the afferent sensory renal nerves in the regulation of blood pressure has received increased attention.

IL-1R Mediated Activation of Renal Sensory Nerves in DOCA-Salt Hypertension.

Background: Clinical trials of renal denervation for the treatment of hypertension have shown a variety of off-target improvements in conditions associated with sympathetic overactivity. This may be due to the ablation of sympathoexcitatory afferent renal nerves, which are overactive under conditions of renal inflammation. Renal IL (interleukin)-1β is elevated in the deoxycorticosterone acetate-salt model of hypertension, and its activity may be responsible for the elevation in afferent renal nerve activity and arterial pressure.

Impact of anesthesia on micromagnetic stimulation (MS) of the vagus nerve.

To treat diseases associated with vagal nerve control of peripheral organs, it is necessary to selectively activate efferent and afferent fibers in the vagus. As a result of the nerve's complex anatomy, fiber-specific activation proves challenging. Spatially selective neuromodulation using micromagnetic stimulation(MS) is showing incredible promise.

Sympathetic Pathophysiology in Hypertension Origins: The Path to Renal Denervation.

The importance of the sympathetic nervous system in essential hypertension has been recognized in 2 eras. The first was in early decades of the 20 century, through to the 1960s. Here, the sympathetic nervous system was identified as a target for the treatment of hypertension, and an extensive range of antiadrenergic therapies were developed.

Investigating patient engagement associations between a postdischarge texting programme and patient experience, readmission and revisit rates outcomes.

Objectives: This study aimed (1) to examine the association between patient engagement with a bidirectional, semiautomated postdischarge texting programme and Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey outcomes, readmissions and revisit rates in a large health system and (2) to describe operational and clinical flow considerations for implementing a postdischarge texting programme.

Setting: The study involved 1 main academic hospital (beds: 2500+) and 6 community hospitals (beds: 190-400, averaging 300 beds per hospital) in Houston, Texas.

Methods: Retrospective, observational cohort study between non-engaged patients (responded with 0-2 incoming text messages) and engaged patients (responded with 3+ incoming, patient-initiated text messages) between December 2022 and May 2023.

Higher arterial stiffness and blunted vagal control of the heart in young women with compared to without a clinical diagnosis of PTSD.

Purpose: Young women are typically thought to be protected from cardiovascular disease (CVD) before menopause. However, posttraumatic stress disorder (PTSD) increases CVD risk in women by up to threefold. Data in predominantly male cohorts point to physiological mechanisms such as vascular and autonomic derangements as contributing to increased CVD risk.

Renal and hypothalamic inflammation in renovascular hypertension: role of afferent renal nerves.

Renal denervation (RDN) is a potential therapy for drug-resistant hypertension. However, whether its effects are mediated by ablation of efferent or afferent renal nerves is not clear. Previous studies have implicated that renal inflammation and the sympathetic nervous system are driven by the activation of afferent and efferent renal nerves.

Periglomerular afferent innervation of the mouse renal cortex.

Recent studies using a novel method for targeted ablation of afferent renal nerves have demonstrated their importance in the development and maintenance of some animal models of hypertension. However, relatively little is known about the anatomy of renal afferent nerves distal to the renal pelvis. Here, we investigated the anatomical relationship between renal glomeruli and afferent axons identified based on transient receptor potential vanilloid 1 channel (TRPV1) lineage or calcitonin gene related peptide (CGRP) immunolabeling.

Neurons of the median preoptic nucleus contribute to chronic angiotensin II-salt induced hypertension in the rat.

Experiments were designed to test the hypothesis that median preoptic (MnPO) neurons are necessary for the full hypertensive response to chronic angiotensin II (AngII) in rats consuming a high salt diet. The MnPO is implicated in many of the physiologic actions of AngII, primarily acting as a downstream nucleus to AngII binding at circumventricular organs such as the organum vasculosum of the lamina terminalis (OVLT). We have previously shown a prominent effect of lesion of the OVLT on the chronic hypertensive effects of AngII in rats consuming high salt.

Structure evolution of nanodiamond aggregates: a SANS and USANS study.

Ultra-small-angle neutron scattering (USANS) and small-angle neutron scattering (SANS) measurements, covering length scales from micrometres to nanometres, were made to investigate the structure of nanodiamonds (NDs) and their suspensions. These nanodiamonds were produced by two different techniques, namely by the detonation method and by the laser ablation of a carbon-hydro-carbon mixture. The (U)SANS results indicated the presence of structures four orders of magnitude larger than the dimensions of a single ND particle, consisting of aggregations of ND particles.

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

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-A mice that express an enzyme that cannot be inactivated by dephosphorylation.

Function of Renal Nerves in Kidney Physiology and Pathophysiology.

Renal sympathetic (efferent) nerves play an important role in the regulation of renal function, including glomerular filtration, sodium reabsorption, and renin release. The kidney is also innervated by sensory (afferent) nerves that relay information to the brain to modulate sympathetic outflow. Hypertension and other cardiometabolic diseases are linked to overactivity of renal sympathetic and sensory nerves, but our mechanistic understanding of these relationships is limited.

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

Renal denervation (RDNX) lowers mean arterial pressure (MAP) in patients with resistant hypertension. Less well studied is the effect of celiac ganglionectomy (CGX), a procedure which involves the removal of the nerves innervating the splanchnic vascular bed. We hypothesized that RDNX and CGX would both lower MAP in genetically hypertensive Schlager (BPH/2J) mice through a reduction in sympathetic tone.

Social stress is lethal in the mdx model of Duchenne muscular dystrophy.

Background: Duchenne muscular dystrophy (DMD) is caused by the loss of dystrophin. Severe and ultimately lethal, DMD progresses relatively slowly in that patients become wheelchair bound only around age twelve with a survival expectancy reaching the third decade of life.

Methods: The mildly-affected mdx mouse model of DMD, and transgenic DysΔMTB-mdx and Fiona-mdx mice expressing dystrophin or utrophin, respectively, were exposed to either mild (scruffing) or severe (subordination stress) stress paradigms and profiled for their behavioral and physiological responses.

Report of the National Heart, Lung, and Blood Institute Working Group on Hypertension: Barriers to Translation.

The National Heart, Lung, and Blood Institute convened a multidisciplinary working group of hypertension researchers on December 6 to 7, 2018, in Bethesda, MD, to share current scientific knowledge in hypertension and to identify barriers to translation of basic into clinical science/trials and implementation of clinical science into clinical care of patients with hypertension. The goals of the working group were (1) to provide an overview of recent discoveries that may be ready for testing in preclinical and clinical studies; (2) to identify gaps in knowledge that impede translation; (3) to highlight the most promising scientific areas in which to pursue translation; (4) to identify key challenges and barriers for moving basic science discoveries into translation, clinical studies, and trials; and (5) to identify roadblocks for effective dissemination and implementation of basic and clinical science in real-world settings. The working group addressed issues that were responsive to many of the objectives of the National Heart, Lung, and Blood Institute Strategic Vision.

Kidney failure, arterial hypertension and left ventricular hypertrophy in rats with loss of function mutation of SOD3.

Chronic kidney disease (CKD) poses a considerable medical and public health challenge, and the Dahl/Salt Sensitive (Dahl/SS) strain is often used for CKD study. Extracellular superoxide dismutase (SOD3) is important for removing extracellular superoxide anions and is highly expressed in renal tissue. Using a novel rat strain with loss-of-function mutation of SOD3 created by replacing glutamate 124 of SOD3 with aspartic acid (SOD3 rat strain), we determined the effect of SOD3 on renal function and blood pressure in Dahl/SS rats.

Renal and Lumbar Sympathetic Nerve Activity During Development of Hypertension in Dahl Salt-Sensitive Rats.

To study the contribution of sympathetic nerve activity (SNA) to the development of hypertension, experiments were designed to continuously and simultaneously measure renal (RSNA) and lumbar SNA (LSNA) during the development of hypertension induced by 8% salt loading in Dahl salt-sensitive (DS) rats. Male DS and salt-resistant rats were instrumented with bipolar electrodes to record RSNA and LSNA and a telemeter to record arterial pressure (AP). AP increased during the first 3 days after the onset of salt loading by ≈10 mm Hg in both DS and Dahl salt-resistant rats.

Renal Denervation for Treating Hypertension: Current Scientific and Clinical Evidence.

Initial studies of catheter-based renal denervation (RDN) for uncontrolled HTN using radiofrequency ablation in the main renal arteries showed that RDN was effective in lowering office blood pressure (BP). However, the first randomized sham-controlled trial, SYMPLICITY-HTN-3, did not show significantly lower office or 24-h ambulatory systolic BP compared with sham treatment. Subsequent studies in both animals and humans demonstrated the potential importance of more distal and branch renal artery radiofrequency ablation, and a second-generation multielectrode system became available.