Prenatal nicotine exposure leads to epigenetic alterations in peripheral nervous system signaling genes in the testis of the rat.

Background: Prenatal nicotine exposure (PNE) has been documented to cause numerous deleterious effects on fetal development. However, the epigenetic changes promoted by nicotine exposure on germ cells are still not well understood.

Objectives: In this study, we focused on elucidating the impact of prenatal nicotine exposure on regulatory epigenetic mechanisms important for germ cell development.

Nicotine Exposure during Rodent Pregnancy Alters the Composition of Maternal Gut Microbiota and Abundance of Maternal and Amniotic Short Chain Fatty Acids.

Tobacco smoking is the leading cause of preventable death. Numerous reports link smoking in pregnancy with serious adverse outcomes, such as miscarriage, stillbirth, prematurity, low birth weight, perinatal morbidity, and infant mortality. Corollaries of consuming nicotine in pregnancy, separate from smoking, are less explored, and the mechanisms of nicotine action on maternal-fetal communication are poorly understood.

Nicotine Induces Maternal and Fetal Inflammatory Responses Which Predispose Intrauterine Infection Risk in a Rat Model.

Introduction: Both smoking and infection adversely impact pregnancy. Previously, our group identified in a rodent model that 6 mg/kg/d nicotine increased the risk of fetal infection at gestation day (GD) 18. Here, we investigate lower nicotine doses.

The importance of bone marrow and the immune system in driving increases in blood pressure and sympathetic nerve activity in hypertension.

New Findings: What is the topic of this review? This manuscript provides a review of the current understanding of the role of the sympathetic nervous system in regulation of bone marrow-derived immune cells and the effect that the infiltrating bone marrow cells may have on perpetuation of the sympathetic over-activation in hypertension. What advances does it highlight? We highlight the recent advances in understanding of the neuroimmune interactions both peripherally and centrally as they relate to blood pressure control.

Abstract: The sympathetic nervous system (SNS) plays a crucial role in maintaining physiological homeostasis, in part by regulating, integrating and orchestrating processes between many physiological systems, including the immune system.

Small-hairpin RNA and pharmacological targeting of neutral sphingomyelinase prevent diaphragm weakness in rats with heart failure and reduced ejection fraction.

Heart failure with reduced ejection fraction (HFREF) increases neutral sphingomyelinase (NSMase) activity and mitochondrial reactive oxygen species (ROS) emission and causes diaphragm weakness. We tested whether a systemic pharmacological NSMase inhibitor or short-hairpin RNA (shRNA) targeting NSMase isoform 3 (NSMase3) would prevent diaphragm abnormalities induced by HFREF caused by myocardial infarction. In the pharmacological intervention, we used intraperitoneal injection of GW4869 or vehicle.

Impact of gestational nicotine exposure on intrauterine and fetal infection in a rodent model.

We investigated the interaction between prenatal nicotine exposure and intrauterine infection using established rat models. Beginning at gestation day (GD) 6, dams were continuously infused with either saline or 6 mg/kg/day nicotine (Nic). At GD 14, dams received either sterile broth or 105 colony-forming units Mycoplasma pulmonis (MP), resulting in four treatment groups: control (4 dams, 33 fetal units); MP only (5 dams, 55 fetal units); Nic only (5 dams, 61 fetal units), and Nic + MP (7 dams, 82 fetal units).

Blockade of orexin receptors attenuates the cardiovascular response to air-jet stress in spontaneously hypertensive rats.

This study tested the hypothesis that orexin plays a role in the elevated pressor response to acute stress in the spontaneously hypertensive rat (SHR). The pressor response to air jet stress (AJS) (n=11/group) was 2.5 times greater in vehicle treated SHR versus Wistar (WIS) rats.

Chronic heart failure alters orexin and melanin concentrating hormone but not corticotrophin releasing hormone-related gene expression in the brain of male Lewis rats.

Objective: The aim of this study was to investigate the effect of chronic heart failure (HF; 16 weeks post left coronary artery ligation) on the brain's orexin (ORX) and related neuropeptide systems.

Methods: Indicators of cardiac function, including the percent fractional shortening (%FS) left ventricular posterior wall shortening velocity (LVPWSV) were assessed via echocardiography at 16 weeks post myocardial infarction or sham treatment in male Lewis rats (n=5/group). Changes in gene expression in HF versus control (CON) groups were quantified by real-time PCR in the hypothalamus, amygdala and dorsal pons.

Brain-derived neurotrophic factor modulates angiotensin signaling in the hypothalamus to increase blood pressure in rats.

Brain-derived neurotrophic factor (BDNF) expression increases in the paraventricular nucleus of the hypothalamus (PVN) in response to hypertensive stimuli including stress and hyperosmolarity. However, it is unclear whether BDNF in the PVN contributes to increases in blood pressure (BP). We tested the hypothesis that increased BDNF levels within the PVN would elevate baseline BP and heart rate (HR) and cardiovascular stress responses by altering central angiotensin signaling.

Effect of DOCA/salt hypertension on CRF expression in the amygdala and the autonomic stress response in conscious rats.

The effects of DOCA/salt treatment on amygdala-area CRF gene expression and the autonomic response to air jet stress (AJS) were evaluated in conscious male Sprague Dawley (SD) rats. Fifteen days of DOCA/salt treatment significantly increased resting arterial pressure (AP), decreased resting heart rate (HR) and significantly reduced regional CRF mRNA compared to controls (23±7% vs. 100±26%) independent of changes in regional CRF receptor expression.

Role of lateral parabrachial opioid receptors in exercise-induced modulation of the hypotensive hemorrhage response in conscious male rats.

Some of the benefits of exercise appear to be mediated through modulation of neuronal excitability in central autonomic control circuits. Previously, we identified that six weeks of voluntary wheel running had a protective effect during hemorrhage (HEM), limiting both the hypotensive phase of HEM and enhancing recovery. The present study was undertaken to evaluate the role of opioid release in the lateral parabrachial nucleus (LPBN) on the response to severe HEM in chronically exercised (EX, voluntary) versus sedentary (SED) controls.

Prenatal nicotine exposure alters postnatal cardiorespiratory integration in young male but not female rats.

The present study tested the hypothesis that prenatal nicotine exposure (PNE) induces sex specific alternations in indices of cardiorespiratory coupling during early development. Rat pups exposed to either nicotine (6 mg/kg/day) or saline (control) in utero were chronically instrumented with ECG electrodes for measurement of heart rate (HR) and respiratory frequency (RF) was monitored by whole body plethysmography on postnatal days (P)13, P16 and P26. PNE had no identifiable effect on resting respiratory frequency (RF) in either sex.

Daily voluntary exercise alters the cardiovascular response to hemorrhage in conscious male rats.

The present study tested the hypothesis that voluntary wheel-exercised rats would better tolerate severe hemorrhage (HEM) compared to age matched sedentary (SED) controls. Conscious rats housed with (EX, n = 8) or without (SED, n = 8) a running wheel for 6 weeks underwent a 30% total blood volume HEM over 15 min and were euthanized 90 min later and brain tissue was processed for Fos-like immunoreactivity (FLI). Both EX and SED groups displayed typical responses to HEM (initial tachycardia followed by decreased HR and MAP) but at the end of HEM, mean arterial pressure (93 ± 6 vs 58 ± 3 mm Hg) and heart rate (316 ± 17 vs.

Sex differences in heart rate variability during sleep following prenatal nicotine exposure in rat pups.

The influence of both prenatal nicotine exposure (PNE; 6 mg/kg/day) and sex on heart rate (HR) regulation during sleep versus wakefulness was evaluated in 13, 16 and 26 day old rat pups. Pups were chronically instrumented at least 24 h before testing. On postnatal day 13 (P13), PNE males spent significantly more time in NREM sleep and demonstrated a greater drop in HR when transitioning from quiet wake to sleep compared to age and sex matched controls (-14±5 bpm versus -1±3 bpm, respectively).

Stress-induced changes in c-Fos and corticotropin releasing hormone immunoreactivity in the amygdala of the spontaneously hypertensive rat.

The present study was undertaken to test the hypothesis that dysregulation of the amygdala contributes to the exaggerated autonomic response to stress in an animal model of essential hypertension. Spontaneously hypertensive (SHR) and normotensive Wistar male rats were chronically instrumented and exposed to 20 min of either air jet stress (AJS) or air noise alone (CON). AJS induced a significant increase in both heart rate and arterial pressure that was greater in the SHR.

Modulation of heart rate variability during severe hemorrhage at different rates in conscious rats.

This study was undertaken to evaluate heart rate (HR) regulation during severe hemorrhage (HEM) at different rates of blood loss. Chronically instrumented male rats underwent HEM at one of three rates: slow (0.5 ml/min/kg; S-HEM), intermediate (1.

Influence of dorsal periaqueductal gray activation on respiratory occlusion reflexes in rats.

The dorsal periaqueductal gray (dPAG) is an essential neural component for central integration of defense behavior and associated autonomic regulation. Electrical and chemical stimulation of this region results in a significant decrease of inspiratory (Ti) and expiratory (Te) breathing durations. In the present study it was hypothesized that breath timing changes elicited by dPAG activation would modulate respiratory load compensation volume-timing reflexes.

Respiratory responses elicited by rostral versus caudal dorsal periaqueductal gray stimulation in rats.

The periaqueductal gray (PAG) is a central neural region essential for defense behavior and coordination of accompanying autonomic responses. Activation of rostral versus caudal dorsal (dPAG) regions mediates different cardiovascular response patterns. Stimulation of the dPAG also elicits increased respiratory activity, however, it is unknown if there is a regional difference in dPAG modulation of respiratory pattern.

Midbrain modulation of the cardiac baroreflex involves excitation of lateral parabrachial neurons in the rat.

Activation of the dorsal periaqueductal gray (PAG) evokes defense-like behavior including a marked increase in sympathetic drive and resetting of baroreflex function. The goal of this study was to investigate the role of the lateral parabrachial nucleus (LPBN) in mediating dorsal PAG modulation of the arterial baroreflex. Reflex responses were elicited by electrical stimulation of the aortic depressor nerve (ADN) at 5 Hz or 15 Hz in urethane anesthetized rats (n=18).

Hemodynamic responses and c-Fos changes associated with hypotensive hemorrhage: standardizing a protocol for severe hemorrhage in conscious rats.

The central mechanisms underlying the transition from compensation to decompensation during severe hemorrhage (HEM) are poorly understood. Furthermore, a lack of consistency in HEM protocols exists in the current literature. This study assessed the cardiovascular response and Fos-like immunoreactivity (FLI) in specific brain regions following severe HEM at three rates (2, 1, or 0.

Respiratory muscle responses elicited by dorsal periaqueductal gray stimulation in rats.

The periaqueductal gray matter is an essential neural substrate for central integration of defense behavior and accompanied autonomic responses. The dorsal half of the periaqueductal gray matter (dPAG) is also involved in mediating emotional responses of anxiety and fear, psychological states that often are associated with changes in ventilation. However, information regarding respiratory modulation elicited from this structure is limited.

Low-dose mirtazapine increases genioglossus activity in the anesthetized rat.

Study Objectives: To examine the effects of mirtazapine on genioglossus and diaphragmatic electromyogram activity in the anesthetized rat.

Design: Parallel-group study.

Subjects: Sprague-Dawley adult male rats, 10 in each of 3 groups were studied.

Activation of the dorsal periaqueductal gray in the rat induces Fos-like immunoreactivity in select non-cholinergic mesopontine neurons.

Autonomic responses evoked from the dorsal periaqueductal gray (dPAG) have been reported to be mediated in part by acetylcholine release in the medulla. To identify the possible origin of cholinergic neurons activated by dPAG stimulation, the pattern of Fos-like immunoreactivity (FLI) in the mesopontine cholinergic cell groups was examined in three groups of urethane anesthetized rats. Relative to surgery (n=6) and blood pressure control groups (n=6), chemical disinhibition of the dPAG (n=10) induced a significant increase in FLI in the lateral dorsal tegmental nucleus (LDTg) but not the pedunculopontine tegmental nucleus.

Parabrachial neurons mediate dorsal periaqueductal gray evoked respiratory responses in the rat.

The neural substrates mediating autonomic components of the behavioral defense response reside in the periaqueductal gray (PAG). The cardiovascular components of the defense response evoked from the dorsal PAG (DPAG) have been well described and are dependent, in part, on the integrity of neurons in the region of the parabrachial nucleus as well as the rostral ventrolateral medulla. Descending pathways mediating the ventilatory response associated with activation of DPAG neurons are unknown.

Increased c-Fos expression in select lateral parabrachial subnuclei following chemical versus electrical stimulation of the dorsal periaqueductal gray in rats.

The parabrachial nucleus (PBN) is located in the rostral dorsolateral pons and has been identified as a critical relay for cardiovascular responses (sympathoexcitation and baroreflex attenuation) evoked by the dorsal periaqueductal gray (PAG). We examined the pattern of c-Fos protein immunoreactivity throughout the rostral-caudal extent of the PBN in four groups of anesthetized male Sprague-Dawley rats to identify the specific PBN regions activated by dorsal PAG stimulation. Both electrical stimulation and chemical (0.