Downregulation of neuronal nitric oxide synthase (nNOS) within the paraventricular nucleus in Ins2-type-1 diabetic mice contributes to sympatho-excitation.

Activation of both renin-angiotensin system (RAS) and the sympathetic system is the primary etiologic event in developing cardiovascular complications in diabetes mellitus (DM). However, the precise mechanisms for sympathetic activation in DM have not been elucidated. Here we attempted to investigate diabetes-linked cardiovascular dysregulation due to angiotensin II (Ang II)-mediated reduction in neuronal nitric oxide (NO) synthase (nNOS) within the paraventricular neuleus (PVN).

Assessing the cooling/lubricating agencies for sustainable alternatives during machining of Nimonic 80: Economic and environmental impacts.

Developing sustainable manufacturing methods that balance environmental and economic aspects is challenging. A comprehensive analysis of the economics of machining and carbon emissions is essential to encourage adopting sustainable practices. This work presents the machinability and comparative sustainability analysis of Nimonic 80 superalloy when it is machined utilizing a novel, environmentally friendly vegetable oil-based hybrid nanofluid-minimum quantity lubrication (MQL) and liquid carbon dioxide (LCO) technique.

Erythrocyte glycocalyx sensitivity to sodium is associated with salt sensitivity of blood pressure in women but not men.

Background: While salt sensitivity of blood pressure (SSBP) is a risk factor for hypertension, end-organ damage and death, most studies are conducted in western countries and in White people. We previously found that the prevalence of SSBP in Blacks living in Sub-Saharan Africa is as high as 75-80% like what has been reported in the west. Erythrocyte glycocalyx sensitivity to sodium (eGCSS), a marker of sodium-induced damage to the erythrocyte and vascular endothelial glycocalyx is thought to be related to blood pressure perturbations associated with salt intake.

Activation of renal epithelial Na channels (ENaC) in infants with congenital heart disease.

Introduction: This study was designed to measure the concentration and activity of urinary proteases that activate renal epithelial sodium channel (ENaC) mediated Na transport in infants with congenital heart disease, a potential mechanism for fluid retention.

Methods: Urine samples from infants undergoing cardiac surgery were collected at three time points: T1) pre-operatively, T2) 6-8 h after surgery, and T3) 24 h after diuretics. Urine was collected from five heathy infant controls.

Hypertension Related Co-Morbidities and Complications in Women of Sub-Saharan Africa: A Brief Review.

Hypertension is the leading cause of cardiovascular disease in women, and sub-Saharan African (SSA) countries have some of the highest rates of hypertension in the world. Expanding knowledge of causes, management, and awareness of hypertension and its co-morbidities worldwide is an effective strategy to mitigate its harms, decrease morbidities and mortality, and improve individual quality of life. Hypertensive disorders of pregnancy (HDPs) are a particularly important subset of hypertension, as pregnancy is a major stress test of the cardiovascular system and can be the first instance in which cardiovascular disease is clinically apparent.

Enhanced central sympathetic tone induces heart failure with preserved ejection fraction (HFpEF) in rats.

Heart failure with preserved ejection fraction (HFpEF) is a heterogenous clinical syndrome characterized by diastolic dysfunction, concentric cardiac left ventricular (LV) hypertrophy, and myocardial fibrosis with preserved systolic function. However, the underlying mechanisms of HFpEF are not clear. We hypothesize that an enhanced central sympathetic drive is sufficient to induce LV dysfunction and HFpEF in rats.

Role of Nanoparticle-Conjugates and Nanotheranostics in Abrogating Oxidative Stress and Ameliorating Neuroinflammation.

Oxidative stress is a deteriorating condition that arises due to an imbalance between the reactive oxygen species and the antioxidant system or defense of the body. The key reasons for the development of such conditions are malfunctioning of various cell organelles, such as mitochondria, endoplasmic reticulum, and Golgi complex, as well as physical and mental disturbances. The nervous system has a relatively high utilization of oxygen, thus making it particularly vulnerable to oxidative stress, which eventually leads to neuronal atrophy and death.

Inhibition of Pyk2 Improves Cx43 Intercalated Disc Localization, Infarct Size, and Cardiac Function in Rats With Heart Failure.

Background: Heart failure causes changes in Cx43 (Connexin43) regulation that are associated with arrhythmic heart disease. Pyk2 (proline-rich tyrosine kinase 2) is activated in cardiomyopathies and phosphorylates Cx43 to decrease intercellular communication. This study was designed to determine if Pyk2 inhibition improves cardiac function in a myocardial infarction (MI)-induced heart failure model in rats.

Glycocalyx-Sodium Interaction in Vascular Endothelium.

The glycocalyx generally covers almost all cellular surfaces, where it participates in mediating cell-surface interactions with the extracellular matrix as well as with intracellular signaling molecules. The endothelial glycocalyx that covers the luminal surface mediates the interactions of endothelial cells with materials flowing in the circulating blood, including blood cells. Cardiovascular diseases (CVD) remain a major cause of morbidity and mortality around the world.

C-type natriuretic peptide (CNP) in the paraventricular nucleus-mediated renal sympatho-inhibition.

Volume reflex produces sympatho-inhibition that is mediated by the hypothalamic paraventricular nucleus (PVN). However, the mechanisms for the sympatho-inhibitory role of the PVN and the neurochemical factors involved remain to be identified. In this study, we proposed C-type natriuretic peptide (CNP) as a potential mediator of this sympatho-inhibition within the PVN.

Neurogenic Background for Emotional Stress-Associated Hypertension.

Purpose Of Review: The response to natural stressors involves both cardiac stimulation and vascular changes, primarily triggered by increases in sympathetic activity. These effects lead to immediate flow redistribution that provides metabolic support to priority target organs combined with other key physiological responses and cognitive strategies, against stressor challenges. This extremely well-orchestrated response that was developed over millions of years of evolution is presently being challenged, over a short period of time.

Sex differences in hypertension among people living with HIV after initiation of antiretroviral therapy.

Background: Hypertension is common in people living with HIV (PLWH) on antiretroviral therapy (ART). In the general population and in experimental animal models, the incidence of hypertension is greater in males than in females, especially during the premenopausal period. However, it is not known whether there are sex differences in hypertension associated with HIV and ART, and the factors contributing to incident hypertension among PLWH have not been well characterized.

Hypertension and human immunodeficiency virus: A paradigm for epithelial sodium channels?

Hypertension is a risk factor for end organ damage and death and is more common in persons with HIV compared to the general population. Several mechanisms have been studied in the pathogenesis of hypertension. Current evidence suggests that the epithelial sodium channel (ENaC) plays a key role in regulating blood pressure through the transport of sodium and water across membranes in the kidney tubules, resulting in retention of sodium and water and an altered fluid balance.

Cardiorenal Syndrome: The Role of Neural Connections Between the Heart and the Kidneys.

The maintenance of cardiovascular homeostasis is highly dependent on tightly controlled interactions between the heart and the kidneys. Therefore, it is not surprising that a dysfunction in one organ affects the other. This interlinking relationship is aptly demonstrated in the cardiorenal syndrome.

A Critical Role for the Paraventricular Nucleus of the Hypothalamus in the Regulation of the Volume Reflex in Normal and Various Cardiovascular Disease States.

Purpose Of Review: This review focuses on studies implicating forebrain neural pathways and neuromodulator systems, particularly, the nitric oxide system within the paraventricular nucleus of the hypothalamus in regulating neurohumoral drive, autonomic pathways, and fluid balance.

Recent Findings: Accumulating evidence from animals with experimental models of hypertension and heart failure as well as humans with hypertension suggests that alterations in central neural pathways, particularly, within the PVN neuromodulated by neuronal nitric oxide, are involved in regulating sympathetic outflow particularly to the kidney resulting in alterations in fluid balance commonly observed in hypertension and heart failure states. The characteristics of the hypertensive and heart failure states include alterations in neuronal nitric oxide within the PVN to cause an increase in renal sympathetic nerve activity to result in sodium and fluid retention in these diseases.

Splenic denervation attenuates repeated social defeat stress-induced T-lymphocyte inflammation.

Background: Post-traumatic stress disorder (PTSD) is a devastating psychological disorder. Patients with PTSD canonically demonstrate an increased risk for inflammatory diseases, as well as increased sympathetic tone and norepinephrine (NE) outflow. Yet, the exact etiology and causal nature of these physiologic changes remain unclear.

Neurogenic Hypertension Mediated Mitochondrial Abnormality Leads to Cardiomyopathy: Contribution of UPR and Norepinephrine-miR- 18a-5p-HIF-1α Axis.

Hypertension increases the risk of heart disease. Hallmark features of hypertensive heart disease is sympathoexcitation and cardiac mitochondrial abnormality. However, the molecular mechanisms for specifically neurally mediated mitochondrial abnormality and subsequent cardiac dysfunction are unclear.

Sympathoinhibition and Vasodilation Contribute to the Acute Hypotensive Response of the Superoxide Dismutase Mimic, MnTnBuOE-2-PyP, in Hypertensive Animals.

The pathogenesis of hypertension has been linked to excessive levels of reactive oxygen species (ROS), particularly superoxide (O), in multiple tissues and organ systems. Overexpression of superoxide dismutase (SOD) to scavenge O has been shown to decrease blood pressure in hypertensive animals. We have previously shown that MnTnBuOE-2-PyP (BuOE), a manganese porphyrin SOD mimic currently in clinical trials as a normal tissue protector for cancer patients undergoing radiation therapy, can scavenge O and acutely decrease normotensive blood pressures.

Enhanced Expression and Function of Renal SGLT2 (Sodium-Glucose Cotransporter 2) in Heart Failure: Role of Renal Nerves.

Background: Recent clinical studies demonstrate that SGLT2 (sodium-glucose cotransporter 2) inhibitors ameliorate heart failure (HF). The present study was conducted to assess the expression and function of renal SGLT2 and the influence of enhanced renal sympathetic tone in HF.

Methods: Four weeks after coronary artery ligation surgery to induce HF, surgical bilateral renal denervation (RDN) was performed in rats.

Role of Renal Sympathetic Nerves in GLP-1 (Glucagon-Like Peptide-1) Receptor Agonist Exendin-4-Mediated Diuresis and Natriuresis in Diet-Induced Obese Rats.

Background The gut-derived hormone GLP-1 (glucagon-like peptide-1) exerts beneficial effects against established risk factors for chronic kidney disease. GLP-1 influences renal function by stimulating diuresis and natriuresis and thus lowering arterial blood pressure. The role of the sympathetic nervous system has been implicated as an important link between obesity with elevated arterial pressure and chronic kidney disease.

Therapeutic effects of masitinib on abnormal mechanoreception in a mouse model of tourniquet-induced extremity ischemia-reperfusion.

Tourniquets are widely used to stop extremity hemorrhage, but their use and subsequent release can result in nerve damage and degeneration, leading to neurological deficits. Increasing evidence has suggested a pivotal role of inflammation in nerve damage and abnormal mechanoreception. In this study, we investigated the therapeutic effects of masitinib (Mas), an anti-neuroinflammatory drug, on the mechanoreception of sensory neurons in a mouse model of tourniquet-induced hind paw ischemia-reperfusion (tourniquet/IR).

A comparison of acute mouse hindlimb injuries between tourniquet- and femoral artery ligation-induced ischemia-reperfusion.

The tourniquet or femoral artery ligation is widely used to stop extremity hemorrhage or create a bloodless operating field in the combat scenario and civilian setting. However, these procedures with subsequent reperfusion also induce ischemia-reperfusion (IR) injuries. To fully evaluate animal models of limb IR injuries, we compared tourniquet- and femoral artery ligation-induced IR injuries in the hindlimb of mice.

Renal denervation based on experimental rationale.

Excessive activation of the sympathetic nervous system is one of the pathophysiological hallmarks of hypertension and heart failure. Within the central nervous system, the paraventricular nucleus (PVN) of the hypothalamus and the rostral ventrolateral medulla in the brain stem play critical roles in the regulation of sympathetic outflow to peripheral organs. Information from the peripheral circulation, including serum concentrations of sodium and angiotensin II, is conveyed to the PVN via adjacent structures with a weak blood-brain barrier.