Temporal and region-specific tau hyperphosphorylation in the medulla and forebrain coincides with development of functional changes in male obese Zucker rats.

Metabolic syndrome (MetS) is associated with development of tauopathies that contribute to cognitive decline. Without functional leptin receptors, male obese Zucker rats (OZRs) develop MetS, and they have increased phosphorylated tau (ptau) with impaired cognitive function. In addition to regulating energy balance, leptin enhances activation of the hippocampus, which is essential for spatial learning and memory.

Preserved glycemic control and baroreflex efficacy in young adult hypertensive female obese Zucker rats.

Obese Zucker rats (OZRs) develop hypertension and hyperinsulinemia by 3 mo of age. Male OZRs also have diminished baroreflex-mediated activation of nucleus tractus solitarius (NTS) and bradycardia, which are improved by correcting their hyperglycemia. Conversely, 3-mo-old female OZRs and lean Zucker rats (LZRs) have equivalent baroreflex-mediated bradycardia that is impaired in 6-mo-old OZRs.

Improved glucose homeostasis in male obese Zucker rats coincides with enhanced baroreflexes and activation of the nucleus tractus solitarius.

Young adult male obese Zucker rats (OZR) develop insulin resistance and hypertension with impaired baroreflex-mediated bradycardia and activation of nucleus tractus solitarius (NTS). Because type 1 diabetic rats also develop impaired baroreflex-mediated NTS activation, we hypothesized that improving glycemic control in OZR would enhance compromised baroreflexes and NTS activation. Fasting blood glucose measured by telemetry was comparable in OZR and lean Zucker rats (LZR) at 12-17 wk.

Exaggerated sympathoexcitatory reflexes develop with changes in the rostral ventrolateral medulla in obese Zucker rats.

Obesity leads to altered autonomic reflexes that reduce stability of mean arterial pressure (MAP). Sympathoinhibitory reflexes such as baroreflexes are impaired, but reflexes that raise MAP appear to be augmented. In obese Zucker rats (OZR) sciatic nerve stimulation evokes larger increases in MAP by unknown mechanisms.

Development of attenuated baroreflexes in obese Zucker rats coincides with impaired activation of nucleus tractus solitarius.

Adult obese Zucker rats (OZR; >12 wk) develop elevated sympathetic nerve activity (SNA) and mean arterial pressure (MAP) with impaired baroreflexes compared with adult lean Zucker rats (LZR) and juvenile OZR (6-7 wk). In adult OZR, baroreceptor afferent nerves respond normally to changes in MAP, whereas electrical stimulation of baroreceptor afferent fibers produces smaller reductions in SNA and MAP compared with LZR. We hypothesized that impaired baroreflexes in OZR are linked to reduced activation of brain stem sites that mediate baroreflexes.

Increasing angiotensin-(1-7) levels in the brain attenuates metabolic syndrome-related risks in fructose-fed rats.

We evaluated effects of chronic intracerebroventricular infusion of angiotensin (Ang)-(1-7) on cardiovascular and metabolic parameters in fructose-fed (FF) rats. After 6 weeks of fructose intake (10% in drinking water), Sprague-Dawley rats were subjected to intracerebroventricular infusion of Ang-(1-7) (200 ng/h; FF+A7 group) or 0.9% sterile saline (FF group) for 4 weeks with continued access to fructose.

Altered regulation of the rostral ventrolateral medulla in hypertensive obese Zucker rats.

Obese Zucker rats (OZR) have elevated sympathetic nerve activity (SNA) and mean arterial pressure (MAP) compared with lean Zucker rats (LZR). We examined whether altered tonic glutamatergic, angiotensinergic, or GABAergic inputs to the rostral ventrolateral medulla (RVLM) contribute to elevated SNA and MAP in OZR. Male rats (14-18 wk) were anesthetized with urethane (1.

Altered sympathetic reflexes and vascular reactivity in rats after exposure to chronic intermittent hypoxia.

Exposure to chronic intermittent hypoxia (CIH) yields persistent elevations in sympathetic nerve activity (SNA) and mean arterial pressure(MAP)with exaggerated sympathetic chemoreflexes. We examined the impact of CIH upon other sympathoexcitatory reflexes and a potential central mechanism underlying the altered regulation of SNA.Male Sprague-Dawley rats were exposed to CIH for 2 weeks (40 s at 6% O2 every 9 min, 8 h day⁻¹).

Attenuated baroreflex control of sympathetic nerve activity in obese Zucker rats by central mechanisms.

Adult obese Zucker rats (OZRs) have reduced sympathetic responses to evoked changes in arterial pressure (AP) compared to lean Zucker rats (LZRs). This study examined whether attenuated sympathetic baroreflexes in OZRs may be due to altered sensory or central mechanisms. The OZRs had elevated baseline splanchnic sympathetic nerve activity (SNA) and mean AP (MAP) compared to age-matched LZRs under urethane anaesthesia (P < 0.

Modulation of the sympathetic response to acute hypoxia by the caudal ventrolateral medulla in rats.

Hypoxia elevates splanchnic sympathetic nerve activity (SNA) with differential effects during inspiration and expiration by unresolved central mechanisms. We examined the hypothesis that cardiovascular-related neurones in the caudal ventrolateral medulla (CVLM) contribute to the complex sympathetic response to hypoxia. In chloralose-anaesthetized, ventilated, vagotomized rats, acute hypoxia (10% O2, 60 s) evoked an increase in SNA (103 +/- 12%) that was characterized by a decrease in activity during early inspiration followed by a prominent rise during expiration.

Glutamatergic inputs to the CVLM independent of the NTS promote tonic inhibition of sympathetic vasomotor tone in rats.

GABAergic neurons in the caudal ventrolateral medulla (CVLM) are driven by baroreceptor inputs relayed via the nucleus tractus solitarius (NTS), and they inhibit neurons in rostral ventrolateral medulla to reduce sympathetic nerve activity (SNA) and arterial pressure (AP). After arterial baroreceptor denervation or lesions of the NTS, inhibition of the CVLM continues to increase AP, suggesting additional inputs also tonically activate the CVLM. This study examined whether the NTS contributes to baroreceptor-independent drive to the CVLM and whether glutamate promotes baroreceptor- and NTS-independent activation of the CVLM to tonically reduce SNA.

Impairment of sympathetic baroreceptor reflexes in obese Zucker rats.

Adult obese Zucker rats (OZRs) have elevated sympathetic vasomotor tone and arterial pressure (AP) with blunted baroreflex-mediated changes in heart rate (HR) compared with adult lean Zucker rats (LZRs). The present study examined whether compromised cardiac baroreflexes are indicative of attenuated sympathetic responses. In addition, because juvenile OZRs have a normal mean AP, we determined whether baroreflexes are fully functional prior to hypertension.

VGLUT1 and VGLUT2 innervation in autonomic regions of intact and transected rat spinal cord.

Fast excitatory neurotransmission to sympathetic and parasympathetic preganglionic neurons (SPN and PPN) is glutamatergic. To characterize this innervation in spinal autonomic regions, we localized immunoreactivity for vesicular glutamate transporters (VGLUTs) 1 and 2 in intact cords and after upper thoracic complete transections. Preganglionic neurons were retrogradely labeled by intraperitoneal Fluoro-Gold or with cholera toxin B (CTB) from superior cervical, celiac, or major pelvic ganglia or adrenal medulla.

Exaggerated cardiovascular stress responses and impaired beta-adrenergic-mediated pressor recovery in obese Zucker rats.

Clinical studies have demonstrated that the pressor response to acute stress is larger in obese versus lean individuals. We therefore tested the hypotheses that the pressor response to behavioral stress is greater in obese (OZRs) versus lean Zucker rats (LZRs) and that reduced beta-adrenergic-mediated vasodilation contributes to the enhanced pressor response. Animals were restrained and subjected to acute pulsatile air jet stress (3 minutes), followed by a poststress period of 20 minutes; beta-adrenergic blockade was achieved with propranolol (5 mg/kg, IV) given 15 minutes before the start of air jet stress.

Systemic cholecystokinin differentially affects baro-activated GABAergic neurons in rat caudal ventrolateral medulla.

Cholecystokinin (CCK) is released after a meal to promote digestion and satiety. Circulating CCK inhibits splanchnic sympathetic nerve activity (sSNA), which may contribute to postprandial increases in mesenteric blood flow. The CCK-induced sympathoinhibition occurs by activation of vagal afferent nerves and inhibition of a subset of presympathetic rostral ventrolateral medullary (RVLM) neurons.

Central respiratory modulation of barosensitive neurones in rat caudal ventrolateral medulla.

The sympathetic nerves that maintain blood pressure are modulated by the central respiratory generator. Neurones in the rostral ventrolateral medulla (RVLM) that drive this sympathetic nerve activity (SNA) also display central respiratory drive (CRD)-related activity, suggesting integration of respiratory and cardiovascular regulatory systems within the brainstem. Whether CRD-related activity in the RVLM is due to direct inputs from central respiratory neurones or modulation of cardiovascular-related neurones that influence the RVLM is not known.

Brain stem control of arterial pressure in chronic arterial baroreceptor-denervated rats.

Interruption of the baroreceptor reflex by transection of afferent nerves (sinoaortic denervation; SAD) or lesions of nucleus tractus solitarius (NTS) elevates sympathetic nerve activity (SNA) and arterial pressure (AP). However, within 1 wk, mean AP returns to normal despite the absence of baroreflexes. In this study, we examine central mechanisms that control AP in chronic baroreceptor-denervated rats.

High-soy diet decreases infarct size after permanent middle cerebral artery occlusion in female rats.

Estrogen is a powerful neuroprotective agent in rodent models of ischemic stroke. However, in humans, estrogen treatment can increase risk of stroke. Health risks associated with hormone replacement have led many women to consider alternative therapies including high-soy diets or supplements containing soy isoflavones, which act as estrogen receptor ligands to selectively mimic some of estrogen's actions.

Reduced plasma volume and mesenteric vascular reactivity in obese Zucker rats.

Obese Zucker rats (OZR) are mildly hypertensive with an apparently elevated sympathetic vasomotor tone compared with lean Zucker rats (LZR). Studies have also suggested enhanced adrenergic pressor reactivity in OZR but assumed comparable baroreflexes, or blood volume-to-body weight ratio, to LZR. In 15-wk-old OZR and LZR, we measured plasma volume and vascular reactivity to norepinephrine (NE) and phenylephrine (PE) with doses evaluated by body weight and plasma volume.

Baro-activated neurons with pulse-modulated activity in the rat caudal ventrolateral medulla express GAD67 mRNA.

GABAergic neurons in the caudal ventrolateral medulla (CVLM) are believed to mediate the sympathetic baroreceptor reflex by inhibiting presympathetic neurons in the rostral ventrolateral medulla (RVLM). Accordingly, some CVLM neurons are activated by increased arterial pressure (AP; baro-activated), have activity strongly modulated by the AP pulse (pulse-modulated), and can be antidromically activated from the RVLM. This study examined whether baro-activated, pulse-modulated CVLM neurons are indeed GABAergic and examined their structures.

Decompensated hemorrhage activates serotonergic neurons in the subependymal parapyramidal region of the rat medulla.

According to prior evidence opioid and serotonin release by lower brain stem neurons may contribute to hemorrhage-induced sympathoinhibition (HISI). Here we seek direct evidence for the activation of opioidergic, GABAergic, or serotonergic neurons by severe hemorrhage in the medulla oblongata. Blood was withdrawn from awake rats (40-50% total volume) causing hypotension and profound initial bradycardia.

The baroreflex and beyond: control of sympathetic vasomotor tone by GABAergic neurons in the ventrolateral medulla.

1. Barosensitive, bulbospinal neurons in the rostral ventrolateral medulla (RVLM), which provide the major tonic excitatory drive to sympathetic vasomotor neurons, are prominently inhibited by GABA. 2.

Opioid signalling in the rat rostral ventrolateral medulla.

1. The present article reviews several aspects of opioid signalling in the rostral ventrolateral medulla (RVLM) and their implications for the neural control of blood pressure. 2.

Vesicular glutamate transporter DNPI/VGLUT2 is expressed by both C1 adrenergic and nonaminergic presympathetic vasomotor neurons of the rat medulla.

The main source of excitatory drive to the sympathetic preganglionic neurons that control blood pressure is from neurons located in the rostral ventrolateral medulla (RVLM). This monosynaptic input includes adrenergic (C1), peptidergic, and noncatecholaminergic neurons. Some of the cells in this pathway are suspected to be glutamatergic, but conclusive evidence is lacking.