The medullary projections of afferent neurons with cell bodies in the petrosal ganglion have been investigated using an antidromic mapping technique. Of ninety‐three units studied, fifty‐eight were shown to patterns discharge indicating that they baroreceptors and thirty‐five showed responses stimuli arterial chemoreceptors. Twelve baroreceptor thirteen chemoreceptor afferents had sufficiently stable unitary discharges permit a detailed estimation some their central stimulation through...

Our previous work indicated that the subfornical organ (SFO) is an important brain sensor of blood-borne proinflammatory cytokines, mediating their central effects on autonomic and cardiovascular function. However, mechanisms by which SFO mediates circulating cytokines remain unclear. We hypothesized act within to upregulate expression excitatory inflammatory mediators drive sympathetic nerve activity. In urethane-anesthetized Sprague–Dawley rats, direct microinjection tumor necrosis factor...

Obesity is characterized by increased circulating levels of the adipocyte-derived hormone leptin, which can increase sympathetic nerve activity and raise blood pressure. A previous study revealed that rats fed a high-fat diet (HFD) have an enhanced hypertensive response to subsequent angiotensin II administration mediated at least, in part, brain renin-angiotensin system proinflammatory cytokines. This tested whether leptin mediates this HFD-induced sensitization II-elicited hypertension...

This study examined the early neurohumoral events in progression of congestive heart failure (CHF) after myocardial infarction (MI) rats. Immediately MI was induced by coronary artery ligation, rats had severely depressed left ventricular systolic function and increased end-diastolic volume (LVEDV). Both indicators CHF underwent dynamic changes over next 6 wk. LVEDV continuously interval, whereas stroke but reached a plateau at 4 Plasma renin activity (PRA), arginine vasopressin, atrial...

The inflammatory milieu of acute myocardial infarction (MI) is theoretically conducive to enhanced cytokine synthesis within the brain. We tested hypothesis that tumor necrosis factor-alpha (TNF-alpha), an indicator proinflammatory activity, increases in brain after MI. MI was induced rats by ligating left anterior descending coronary artery and confirmed echocardiography. Plasma tissue levels TNF-alpha were measured using ELISA; mRNA with real-time PCR. Heart, brain, plasma samples obtained...

Blocking brain mineralocorticoid receptors (MRs) reduces the high circulating levels of tumor necrosis factor (TNF)-α in heart failure (HF) rats. TNF-α and other proinflammatory cytokines activate neurons paraventricular nucleus (PVN) hypothalamus, including corticotropin-releasing hormone (CRH) neurons, by inducing cyclooxygenase (COX)-2 activity synthesis prostaglandin E 2 perivascular cells cerebral vasculature. We tested hypothesis that systemic treatment with a MR antagonist would...

The mineralocorticoid (MC) receptor antagonist spironolactone (SL) improves morbidity and mortality in patients with congestive heart failure (CHF). We tested the hypothesis that central nervous system actions of SL contribute to its beneficial effects. (100 ng/h for 28 days) or ethanol vehicle (VEH) was administered intracerebroventricularly intraperitoneally rats CHF induced by coronary artery ligation (CL) SHAM-operated controls. intracerebroventricular treatment prevented increase sodium...

In pathophysiological conditions, increased blood-borne TNF-α induces a broad range of biological effects, including activation the hypothalamic-pituitary-adrenal axis and sympathetic drive. urethane-anesthetized adult Sprague-Dawley rats, we examined mechanisms by which activates neurons in paraventricular nucleus (PVN) hypothalamus rostral ventrolateral medulla (RVLM), two critical brain regions regulating drive normal conditions. (0.5 μg/kg), administered intravenously or into ipsilateral...

The paraventricular nucleus (PVN) of the hypothalamus has critical homeostatic functions, including regulation fluid balance and sympathetic drive. It been suggested that altered activity this contributes to progression congestive heart failure (HF). We hypothesized forebrain influences renin-angiotensin-aldosterone system augment PVN neurons in HF. rate ( n = 68) from rats with ischemia-induced HF was higher than 42) sham-operated controls (8.7 ± 0.8 vs. 2.7 0.3 spikes/s, P < 0.001,...

Aldosterone acts upon mineralocorticoid receptors in the brain to increase blood pressure and sympathetic nerve activity, but mechanisms are still poorly understood. We hypothesized that aldosterone increases activity by upregulating renin-angiotensin system (RAS) oxidative stress brain, as it does peripheral tissues. In Sprague-Dawley rats, (Aldo) or vehicle (Veh) was infused for 1 wk via an intracerebroventricular (ICV) cannula, while RU-28318 (selective receptor antagonist), Tempol...

The brain renin-angiotensin system (RAS) contributes to increased sympathetic drive in heart failure (HF). factors upregulating the RAS HF remain unknown. We hypothesized that aldosterone (ALDO), a downstream product of systemic crosses blood-brain barrier, signals increase activity HF. examined relationship between circulating and ALDO normal intact rats, adrenalectomized rats receiving subcutaneous infusions ALDO, with ischemia-induced sham-operated controls. Brain levels were proportional...

Inflammation is associated with increased sympathetic drive in cardiovascular diseases. Blood-borne proinflammatory cytokines, markers of inflammation, induce cyclooxygenase 2 (COX-2) activity perivascular macrophages the blood-brain barrier. COX-2 generates prostaglandin E , which may enter brain and increase nerve activity. We examined contribution this mechanism to augmented rats after myocardial infarction (MI). Approximately 24 hours acute MI, received an intracerebroventricular...

The expression of proinflammatory cytokines increases in the hypothalamus rats with heart failure (HF). pathophysiological significance this observation is unknown. We hypothesized that hypothalamic upregulate activity central neural systems contribute to increased sympathetic nerve HF, specifically, brain renin-angiotensin system (RAS) and hypothalamic-pituitary-adrenal (HPA) axis. Rats HF induced by coronary ligation sham-operated controls (SHAM) were treated for 4 wk a continuous...

Post‐synaptic responses evoked in neurones of the nucleus tractus solitarius by electrical stimulation carotid sinus, aortic and vagal nerves, alone or combination, have been studied anaesthetized cats using both extracellular intracellular recording techniques. A total 292 received an input from at least one three nerves tested. The activity large majority these cells (249) could only be shown to altered 222 cases this was excitatory response. These showed expected post‐synaptic...

ANG II type 1 receptors (AT(1)R) mediate most of the central effects on cardiovascular function, fluid homeostasis, and sympathetic drive. The mechanisms regulating AT(1)R expression in brain are unknown. In some tissues, can be upregulated by prolonged exposure to II. We examined hypothesis that upregulates stimulating intracellular mitogen-activated protein kinase (MAPK) signaling pathway. Using molecular immunochemical approaches, we phosphorylated MAPK paraventricular nucleus...

Proinflammatory cytokines play an important role in regulating autonomic and cardiovascular function hypertension heart failure. Peripherally administered proinflammatory cytokines, such as tumor necrosis factor-α (TNF-α) interleukin-1β (IL-1β), act on the brain to increase blood pressure, rate, sympathetic nerve activity. These molecules are too large penetrate blood–brain barrier, so mechanisms by which they elicit these responses remain unknown. We tested hypothesis that subfornical organ...

Obesity has been shown to promote renin–angiotensin system activity and inflammation in the brain be accompanied by increased sympathetic blood pressure. Our previous studies demonstrated that administration of a subpressor dose angiotensin (Ang) II sensitizes subsequent Ang II–elicited hypertension. The present study tested whether high-fat diet (HFD) feeding also hypertensive response HFD-induced sensitization is mediated an increase inflammatory mechanisms brain. HFD did not baseline...

Within minutes of acute myocardial infarction (MI), proinflammatory cytokines increase in the brain, heart, and plasma. We hypothesized that cardiac afferent nerves stimulated by injury signal brain to central cytokines. Urethane-anesthetized male Sprague-Dawley rats underwent ligation left anterior descending coronary artery (LAD) or sham LAD after bilateral cervical vagotomy, application a 10% phenol solution epicardial surface myocardium at risk. MI caused significant tumor necrosis...

The purpose of these studies was to determine the effects L-arginine-derived nitric oxide (NO) synthesis on neuronal activity in solitary tract nucleus (NTS) neurons. Single unit recorded extracellularly from medial NTS neurons Fischer-344 rats vivo and vitro. In anesthetized with arterial pressure maintained constant, NG-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg iv), an inhibitor NO synthesis, decreased discharge rate 12 14 increased two. After injection L-NAME, slowing began within...

Depression is an important public health problem and considered to be independent risk factor for coronary artery disease. The pathophysiological mechanisms that link depression with adverse cardiovascular events (e.g., myocardial ischemia, infarction, sudden death) are not well established. It possible increased susceptibility life-threatening cardiac arrhythmias in depressed patients influences the of morbidity mortality This idea was tested use experimental model developed induce...

1. We used a model of bilateral carotid sinus nerve (CSN) stimulation to investigate cardiovascular afferent interactions in nucleus tractus solitarius (NTS) anesthetized cats. In some instances, with inputs from vagus or renal nerves were also examined. 2. Intracellular recordings made 88 NTS neurons activated by electrical one both CSNs. Excitatory (EPSPs), inhibitory (IPSPs), and combined excitatory (EPSP/IPSP) postsynaptic membrane potential responses ipsilateral CSN observed. The input...