Decrease In Sympathetic Nerve Activity Research Articles

Celiac and superior mesenteric ganglia removal improves glucose tolerance and reduces pancreas islet size

The sympathetic nervous system is crucial for the regulation of visceral organ function. For instance, the activation of the sympathetic nervous system promotes glycogenolysis in the liver and modulates glucagon and insulin release from the pancreas, thereby raising blood glucose levels. A decrease in sympathetic nerve activity has the opposite effect. Although such acute effects of sympathetic activity changes have been studied, their long-term outcomes have not been previously examined. In this study, we removed the celiac/superior mesenteric ganglia, where sympathetic postganglionic neurons innervating pancreas and liver locate, and examined its effects on glucose homeostasis and islet size several weeks after surgery. Consistent with the reduction in gluconeogenesis, glucose tolerance improved in gangliectomized mice. However, contrary to our expectation that the inhibition of pancreatic function by sympathetic nerves would be relieved with gangliectomy, insulin or C-peptide release did not increase. Examining the size distribution of pancreatic islets, we identified that the gangliectomy led to a size reduction in large islets and a decrease in the proportion of α and β cells within each islet, as analyzed by immunostaining for insulin and glucagon, respectively. These results indicate that the absence of sympathetic nerve activity reduces the size of the pancreatic islets within a few weeks to reinstate the homeostatic mechanism of blood glucose levels.

Plank exercise improves respiratory capacity through positive changes in body composition, abdominis function, and autonomic nerves' activities

AbstractThis research aimed to explore the impact of plank exercise training (PET) on respiratory function, body composition, abdominis performance, and autonomic nervous system (ANS). Sixty‐one young adults participated and were divided into a control group (CG, n = 31) and an exercise group (EG, n = 30), wherein PET was administered 3 days per week for 12 weeks. After the experiment, the body composition of the CG deteriorated, whereas that of the EG improved (p < 0.001). The EG exhibited a reduction of ∼34% in the mean maximum displacement and a rise of ∼20% in the mean contraction time of the abdominis. The sit‐up in the EG demonstrated a significant increase of ∼55%. In the EG, there was a substantial increase in peak expiratory force by ∼24% and forced expiratory volume in 1 s by ∼14%, accompanied by a reduction in resting respiratory rate by ∼ −9%. When compared to the CG, these alterations were significant between the two groups (p = 0.001). In the EG, there was a significant decrease in resting heart rate by ∼2%, accompanied by a decrease in sympathetic nervous activity by ∼ −5% and by an increase in parasympathetic nervous activity by ∼5%. When compared to the CG, these alterations were significant between the two groups (p = 0.001). The findings of this study revealed that implementing PET in young adults, while controlling for dietary intake and physical activity, resulted in noteworthy changes in respiratory capacity. These changes were coupled with improvements in body composition, abdominal functions, and the ANS.

Abstract 16157: Catheter Ablation Induces an Increase in Heart Rate With Discordant With a Decrease in Sympathetic Nerve Activity in Patients With Paroxysmal Atrial Fibrillation

Background/Introduction: Paroxysmal atrial fibrillation (PAF) is the most common arrhythmia and catheter ablation (CA) is selected with the aim of rhythm control. CA was reported to increase heart rate (HR), which explains the modulation on the cardiac autonomic nervous system. However, little is known about the relationship between heart rate, sympathetic nerve activity and parasympathetic nerve activity in patient with PAF. Purpose: The purpose of this study was to evaluate the effect of CA on direct recording of muscle sympathetic nerve activity (MSNA) and heart rate variability (HRV), and these influences on HR. Methods: This study was conducted as a prospective, observational study. Patients with PAF who were scheduled for CA were enrolled. We measured blood pressure, HR, body weight, brain natriuretic peptide (BNP), echocardiogram parameters, high frequency component as cardiac parasympathetic nerve activity and low frequency component as cardiac sympathetic nerve activity in HRV, and MSNA before and 12 weeks after CA. Results: 21 PAF patients participated in this study. After CA, E/e’ and Ln BNP were significantly reduced(10.6±2.9 to 9.2±2.6, p<0.05. 3.8±1.3 to 3.3±1.6 log/pg/ml, p<0.05, respectively) while no significant changes were observed in EF, SV, left atrial diameter, left ventricular end diastolic and systolic diameters. HR was significantly increased (61.3±7.8 to 71.1±7.6 beats/min, p<0.05, respectively). However, the MSNA burst incidence and frequency were significantly decreased (65.4±12.6 to 41.3±13.4 bursts/100beats, p<0.01, n=21. 39.8±8.8 to 28.1±9.6 bursts/min, p<0.01, n=21. respectively). Also, the reduction in MSNA burst frequency was correlated with the increase in HR (r=0.57, 95%CI 0.183-0.804, p=0.00702). Ln Low frequency component in HRV was significantly decreased (5.72±1.75 to 3.85±2.13 log/ms 2 , p<0.05, n=12), but Ln high frequency (HF) component was not changed . No significant relationship observed between increased HR and HF component. Conclusion: CA induced paradoxical increasing heart rate with the reduction in sympathetic nerve activity in patient with PAF. These findings suggest that CA might modulate autonomic interaction between sinus nodes and in left atrium with denervated in ganglionated plexi.

Physiological Effects of Viewing Bonsai in Elderly Patients Undergoing Rehabilitation.

The benefits of various nature-derived stimuli that can be used for stress relief and relaxation has recently gained immense attention; however, there are very few studies about their influence on elderly patients. The present study aims to present the effects of viewing bonsai on autonomic nervous activity, prefrontal cortex activity, and subjective assessment findings of psychological relaxation in elderly patients undergoing rehabilitation. Fourteen participants aged 64–91 years (mean age ± standard deviation, 78.6 ± 9.6 years) participated in this study. Miniature potted 10-year-old Japanese cypress bonsai trees were used as visual stimuli. Participants viewed the bonsai for 1 min, and the control comprised of no experimental stimulus. Physiological effects on autonomic nervous activity were assessed by measuring the heart rate variability (HRV) and pulse rate. The effects on prefrontal cortex activity were determined using near-infrared spectroscopy, which involved assessment of oxyhemoglobin concentrations in the left and right prefrontal cortices. Subjective evaluations were achieved by the modified semantic differential method. Viewing bonsai resulted in a significant increase in parasympathetic nervous activity, a significant decrease in sympathetic nervous activity, and a significant increase in the perceptions of feeling “comfortable” and “relaxed.” In conclusion, our findings indicated that viewing bonsai induces physiological and psychological relaxation.

Ingestion of coffee polyphenols suppresses deterioration of skin barrier function after barrier disruption, concomitant with the modulation of autonomic nervous system activity in healthy subjects.

The aim of this study was to evaluate the effect of consumption of coffee polyphenols (CPPs) on the autonomic nervous system activity and decreased skin barrier function caused by sodium dodecyl sulfate (SDS) treatment. In this single-blind, placebo-controlled study, ten healthy male subjects consumed either a beverage containing CPPs or a placebo beverage for four weeks. CPPs significantly suppressed the deterioration in skin barrier function and skin moisture content induced by SDS treatment after the third week. Furthermore, in the heart rate variability analysis, CPPs significantly produced an increase in parasympathetic nervous activity, and a decrease in sympathetic nervous activity after the four weeks of beverage consumption. These results suggest that CPPs might influence the regulation of the autonomic nervous system and contribute to the suppressive effect on deterioration of skin barrier function.

Glucose Metabolic Changes in the Brain and Muscles of Patients with Nonspecific Neck Pain Treated by Spinal Manipulation Therapy: A [18F]FDG PET Study.

Objective. The aim of this study was to investigate changes in brain and muscle glucose metabolism that are not yet known, using positron emission tomography with [18F]fluorodeoxyglucose ([18F]FDG PET). Methods. Twenty-one male volunteers were recruited for the present study. [18F]FDG PET scanning was performed twice on each subject: once after the spinal manipulation therapy (SMT) intervention (treatment condition) and once after resting (control condition). We performed the SMT intervention using an adjustment device. Glucose metabolism of the brain and skeletal muscles was measured and compared between the two conditions. In addition, we measured salivary amylase level as an index of autonomic nervous system (ANS) activity, as well as muscle tension and subjective pain intensity in each subject. Results. Changes in brain activity after SMT included activation of the dorsal anterior cingulate cortex, cerebellar vermis, and somatosensory association cortex and deactivation of the prefrontal cortex and temporal sites. Glucose uptake in skeletal muscles showed a trend toward decreased metabolism after SMT, although the difference was not significant. Other measurements indicated relaxation of cervical muscle tension, decrease in salivary amylase level (suppression of sympathetic nerve activity), and pain relief after SMT. Conclusion. Brain processing after SMT may lead to physiological relaxation via a decrease in sympathetic nerve activity.

Post-Exercise Hypotension Is Mediated by a Decrease in Sympathetic Nerve Activity in Stages 2-3 CKD

Background: This study aimed at evaluating the after effects of a single bout of aerobic exercise on muscle sympathetic nerve activity (MSNA), peripheral vascular resistance and blood pressure (BP) in stages 2-3 chronic kidney disease (CKD) patients. We hypothesized that CKD patients present a greater decline in these variables after the exercise than healthy individuals. Methods: Nine patients with stages 2-3 CKD (50 ± 8 years) and 12 healthy volunteers (50 ± 5 years) underwent 2 sessions, conducted in a random order: exercise (45 min, cycle ergometer, 50% of peak oxygen uptake) and rest (seated, 45 min). Sixty minutes after either intervention, MSNA (by microneurography), BP (by oscillometry), and forearm vascular resistance (FVR) were measured. A 2-way analysis of variance with group (between) and session (within) as main factors was employed, accepting p < 0.05 as significant. Results: Diastolic BP and MSNA were higher in the CKD than the control group in both sessions. Responses after exercise were similar in both groups. Systolic BP, diastolic BP, MSNA and FVR were significantly lower after the exercise than after the rest session in both the CKD and the control groups (162 ± 15 vs. 152 ± 23 and 155 ± 11 vs. 145 ± 16 mm Hg, 91 ± 11 vs. 85 ± 14 and 77 ± 5 vs. 71 ± 10 mm Hg, 38 ± 4 vs. 31 ± 4 and 34 ± 2 vs. 27 ± 4 burst/min, 59 ± 29 vs. 41 ± 29 and 45 ± 20 vs. 31 ± 8 U, respectively, all p < 0.05). Conclusion: These results showed that aerobic exercise may produce hemodynamic and neural responses that can be beneficial to these patients in spite of CKD.

Mongolian low birth weight young adults have higher risk of hypertension compared with Han Chinese and Japanese counterparts

Low birth weight (LBW) was confirmed as a risk of high blood pressure (BP) in later stages of life (Barker DJ et al, 1989). Low‐grade inflammation and deterioration of autonomic regulation play an important role in hypertension. However, the associations with birth weight are poorly understood. We examined these relationships among Mongolian, Han Chinese and Japanese young adults, and investigated whether ethnicity affected these relationships. We measured BP and heart rate variability at rest and during postural change from a supine to a sitting position in 16 Mongolian, 4 Han Chinese and 21 Japanese healthy volunteers aged 18–34 years. Blood cell counts, and total cholesterol, high‐density lipoprotein cholesterol (HDL‐C), low‐density lipoprotein cholesterol, triglyceride, and high sensitivity C‐reactive protein levels were measured. Mongolians had lower levels of HDL‐C than did the Japanese (p &lt; 0.01) and the Han Chinese. In Mongolians, the platelet count was higher in the LBW group than in the normal birth weight (NBW) group (p &lt; 0.05). Following postural change, systolic blood pressure and heart rate showed no significant increases in the Mongolian and Japanese LBW groups, whereas the NBW groups had normal responses (p &lt; 0.05). The Mongolian LBW group displayed a slight decrease in sympathetic nerve activity from a supine to a sitting position, although it increased in the Japanese LBW group (p &lt; 0.05). These relationships were not able to examine in Han Chinese because of the small sample size. We suggested that Mongolian low birth weight young adults have higher risk of hypertension compared with Han Chinese and Japanese counterparts.

Actions of circulating angiotensin II and aldosterone in the brain contributing to hypertension.

In the past 1-2 decades, it has become apparent that the brain renin-angiotensin-aldosterone system (RAAS) plays a crucial role in the regulation of blood pressure (BP) by the circulating RAAS. In the brain, angiotensinergic sympatho-excitatory pathways do not contribute to acute, second-to-second regulation but play a major role in the more chronic regulation of the setpoint for sympathetic tone and BP. Increases in plasma angiotensin II (Ang II) or aldosterone and in cerebrospinal fluid [Na(+)] can directly activate these pathways and chronically further activate/maintain enhanced activity by a slow neuromodulatory pathway involving local aldosterone, mineralocorticoid receptors (MRs), epithelial sodium channels, and endogenous ouabain. Blockade of any step in this slow pathway prevents Ang II-, aldosterone-, or salt and renal injury-induced forms of hypertension. It appears that the renal and arterial actions of circulating aldosterone and Ang II act as amplifiers but are not sufficient to cause chronic hypertension if their central actions are prevented, except perhaps at high concentrations. From a clinical perspective, oral treatment with an angiotensin type 1 (AT1)-receptor blocker at high doses can cause central AT1-receptor blockade and, in humans, lower sympathetic nerve activity. Low doses of the MR blocker spironolactone appear sufficient to cause central MR blockade and a decrease in sympathetic nerve activity. Integrating the brain actions of the circulating RAAS with its direct renal and arterial actions provides a better framework to understand the role of the circulating RAAS in the pathophysiology of hypertension and heart failure and to direct therapeutic strategies.

Hypotensive effects of ghrelin receptor agonists mediated through a novel receptor

Some agonists of ghrelin receptors cause rapid decreases in BP. The mechanisms by which they cause hypotension and the pharmacology of the receptors are unknown. The effects of ligands of ghrelin receptors were investigated in rats in vivo, on isolated blood vessels and on cells transfected with the only molecularly defined ghrelin receptor, growth hormone secretagogue receptor 1a (GHSR1a). Three agonists of GHSR1a receptors, ulimorelin, capromorelin and CP464709, caused a rapid decrease in BP in the anaesthetized rat. The effect was not reduced by either of two GHSR1a antagonists, JMV2959 or YIL781, at doses that blocked effects on colorectal motility, in vivo. The rapid hypotension was not mimicked by ghrelin, unacylated ghrelin or the unacylated ghrelin receptor agonist, AZP531. The early hypotension preceded a decrease in sympathetic nerve activity. Early hypotension was not reduced by hexamethonium or by baroreceptor (sino-aortic) denervation. Ulimorelin also relaxed isolated segments of rat mesenteric artery, and, less potently, relaxed aorta segments. The vascular relaxation was not reduced by JMV2959 or YIL781. Ulimorelin, capromorelin and CP464709 activated GHSR1a in transfected HEK293 cells at nanomolar concentrations. JMV2959 and YIL781 both antagonized effects in these cells, with their pA2 values at the GHSR1a receptor being 6.55 and 7.84. Our results indicate a novel vascular receptor or receptors whose activation by ulimorelin, capromorelin and CP464709 lowered BP. This receptor is activated by low MW GHSR1a agonists, but is not activated by ghrelin.

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. In conscious adult rats, a hydralazine (HDZ)-induced reduction in MAP evoked tachycardia that was initially blunted in OZR, but equivalent to LZR within 5 min. In agreement, HDZ-induced expression of c-Fos in the rostral ventrolateral medulla (RVLM) was comparable between groups. In contrast, phenylephrine (PE)-induced rise in MAP evoked markedly attenuated bradycardia with dramatically reduced c-Fos expression in the nucleus tractus solitarius (NTS) of adult OZR compared with LZR. However, in juvenile rats, PE-induced hypertension evoked comparable bradycardia in OZR and LZR with similar or augmented c-Fos expression in NTS of the OZR. In urethane-anesthetized rats, microinjections of glutamate into NTS evoked equivalent decreases in SNA, heart rate (HR), and MAP in juvenile OZR and LZR, but attenuated decreases in SNA and MAP in adult OZR. In contrast, microinjections of glutamate into the caudal ventrolateral medulla, a target of barosensitive NTS neurons, evoked comparable decreases in SNA, HR, and MAP in adult OZR and LZR. These data suggest that OZR develop impaired glutamatergic activation of the NTS, which likely contributes to attenuated baroreflexes in adult OZR.

Blood pressure regulation IV: adaptive responses to weightlessness

During weightlessness, blood and fluids are immediately shifted from the lower to the upper body segments, and within the initial 2 weeks of spaceflight, brachial diastolic arterial pressure is reduced by 5 mmHg and even more so by some 10 mmHg from the first to the sixth month of flight. Blood pressure thus adapts in space to a level very similar to that of being supine on the ground. At the same time, stroke volume and cardiac output are increased and systemic vascular resistance decreased, whereas sympathetic nerve activity is kept surprisingly high and similar to when ground-based upright seated. This was not predicted from simulation models and indicates that dilatation of the arteriolar resistance vessels is caused by mechanisms other than a baroreflex-induced decrease in sympathetic nervous activity. Results of baroreflex studies in space indicate that compared to being ground-based supine, the carotid (vagal)-cardiac interaction is reduced and sympathetic nerve activity, heart rate and systemic vascular resistance response more pronounced during baroreflex inhibition by lower body negative pressure. The future challenge is to identify which spaceflight mechanism induces peripheral arteriolar dilatation, which could explain the decrease in blood pressure, the high sympathetic nerve activity and associated cardiovascular changes. It is also a challenge to determine the cardiovascular risk profile of astronauts during future long-duration deep space missions.

Forest Medicine Research in Japan

There has been growing attention on the effects of forest on physiological relaxation and immune recovery, particularly in forest medicine research, from a perspective of preventive medicine. Japan is a world leader in the accumulation of scientific data on forest medicine research. In this review, we summarize the research that has been conducted in this area since 1992. We conducted field experiment, involving 420 subjects at 35 different forests throughout Japan. After sitting in natural surroundings, these subjects showed decrease in the following physiological parameters compared with those in an urban control group: 12.4% decrease in the cortisol level, 7.0% decrease in sympathetic nervous activity, 1.4% decrease in systolic blood pressure, and 5.8% decrease in heart rate. This demonstrates that stressful states can be relieved by forest therapy. In addition, it should be noted that parasympathetic nervous activity was enhanced by 55.0%, indicating a relaxed state. The results of walking experiments provided similar results. Li et al. demonstrated that immune function was enhanced by forest therapy in middle-aged employees who volunteered to participate in these experiments. Natural killer cell activity, an indicator of immune function, was enhanced by 56% on the second day and returned to normal levels. A significant increase of 23% was maintained for 1 month even after returning to urban life, clearly illustrating the preventive benefits of forest therapy. In an indoor room experiment, we conducted tests with the following: 1) olfactory stimulation using wood smell, 2) tactile stimulation using wood, and 3) auditory stimulation using forest sounds. These indoor stimulations also decreased the blood pressure and pulse rate, and induced a physiological relaxation effect. We anticipate that forest medicine will play an increasingly important role in preventive medicine in the future.

Evaluations of effects of high rebound and low rebound mattress pads on nocturanl sleep and its associated physiology

Recently, several new materials for mattresses become introduced. Although some of these, such as low rebound (or pressure-absorbing) and high rebound mattresses have fairly different characteristics, effects of these mattresses on sleep have never evaluated. In the current study, we have evaluated effects of airweave (a high rebound [HR] mattresses using a highly breathable material) on sleep and its associated physiology and the effects were compared to those of a low rebound mattress (LR). The study was conducted in 10 healthy males, with a randomized cross over single-blind design of one night PSG (23:00 to 7:00) at the sleep laboratory with 1–2 day intervals. The mattress pads were placed on regular beds equipped in the laboratory. The mean age ( ± SD) of the 10 subjects was 26.7 ± 7.7 yrs, height, 169.6 ± 6.3 m, weight, 61.9 ± 5.2 kg, BMI, 21.2 ± 1.7, PSQID, 3.0 ± 0.7, 3% ODI, 2.3 ± 1.1, RDI, 1.8 ± 1.2. In addition to the PSG, number of roll-over during sleep, autonomic nerve activity (by monitoring EKG heart rate variability), core rectal temperature monitoring were assessed. Subjective sleep evaluations were done on the following morning, using visual analogue scales (good sleep [VAS-S] and performance [VAS-P] ) and the Stanford sleepiness scale (SSS). Performance was also evaluated with psychomotor vigilance test (PVT). The significances of the effects (between HR and LR) were evaluated with the paired- t test, except effects of rectal temperature monitoring for which a repeated measures ANOVA with a grouping factor (mattress types) was applied. Subjects slept quickly with both HR (7.1 ± 2.1 min) and LR (9.1 ± 2.6 min). Interestingly, the core body temperature was rapidly and continuously decreased with HR and reached the nadir (36.0 °C) at 2:00–3:00 while decline of the temperature with LR was modest and retained 0.4 °C higher than that with HR between 1:00 and 2:00. A significant increase in Stage 4 sleep was found with HR between 23:00 and 1:00. In addition, decrease in sympathetic nerve activity was prominent with HR between 23:00 and 1:00. There was non-significant tendency to decline in numbers of rollover and elapsed time to fall in sleep after the rollover with HR. Subjective wakefulness and performance in the next morning with HR was improved marginally significantly. Our results suggest that effective heat loss during the initial phase of sleep occurred with HR (i.e., Airweave), and this may facilitate restorative sleep. This study is supported by Airweave Inc.

Adaptive servo-ventilation improves exercise oscillatory ventilation and ventilatory inefficiency in patients with heart failure and central sleep apnea

BackgroundAdaptive servo-ventilation (ASV) can improve ventilatory inefficiency and exercise oscillatory ventilation (EOV) in patients with heart failure (HF) and central sleep apnea (CSA). Although these improvements might originate from both increase in cardiac function and decrease in sympathetic nerve activity, mechanisms underlying the interrelationship remain unknown. MethodsWe compared cardiopulmonary exercise test, muscle sympathetic nerve activity (MSNA) and echocardiography findings at baseline and 3.5±0.8months (mean±SD) of follow-up in 28 patients with both HF (New York Heart Association functional class II and III; left ventricular ejection fraction (LVEF)<45%) and CSA (apnea–hypopnea index (AHI)≥15/h). Of these, 17 patients consented (ASV group) and 11 patients declined (non-ASV group) to undergo ASV treatment. Compliance with ASV and changes in AHI were determined from data collected by integral counters. ResultsVE/VCO2-slope and EOV amplitude at baseline were positively correlated with MSNA, but not with LVEF. ASV therapy reduced VE/VCO2-slope and EOV amplitude (both p<0.01) in association with decrease in MSNA (p<0.01) and increase in LVEF (p<0.001). In non-ASV group, however, these parameters remained unchanged. Change in VE/VCO2-slope was correlated with both change in AHI and average use of ASV. By contrast, change in EOV amplitude was correlated with change in AHI. Changes in VE/VCO2-slope and EOV amplitude were correlated with changes of MSNA (p<0.05), but not with those in LVEF. ConclusionsASV improves ventilatory inefficiency and EOV probably via suppression of CSA and its sympathoinhibitory effect.

Nonlinear Analysis of Drivers Heart Rate Variability on the Prairie Highway

The nonlinear analysis of HRV index can effectively evaluate the drivers mental and physiological stress reaction during driving. By collecting drivers ECG signal on the Prairie Highway and based on nonlinear analysis of HRV, it is found the drivers Correlation Dimension (D2) changes significantly and has a strong negative correlation with driving time, and the regression model under the Prairie Highway environment has been built in this paper. Combining the difference test between the dynamic and static index, the study has concluded drivers sympathetic nerve activity decrease after continuous driving for 30min, and D2 is 2.034-2.593 after 110min.The complexity of drivers autonomic nervous system and the adjust ability of adapting to the environment decrease significantly on the Prairie Highway. These will offer the theoretical basis for monitoring driver fatigue and designing Prairie Highway.

Mechanisms of cardiovascular actions of urocortins in the hypothalamic arcuate nucleus of the rat

The presence of urocortins (UCNs) and corticotropin-releasing factor (CRF) receptors has been reported in the hypothalamic arcuate nucleus (ARCN). We have previously reported that UCNs are involved in central cardiovascular regulation. Based on this information, we hypothesized that the ARCN may be one of the sites where UCNs exert their central cardiovascular actions. Experiments were done in artificially ventilated, adult male Wistar rats anesthetized with urethane. Unilateral microinjections (30 nl) of UCN1 (0.12-2 mM) elicited decreases in mean arterial pressure (MAP) and heart rate (HR). Maximum cardiovascular responses were elicited by a 1 mM concentration of UCN1. Microinjections of UCN2 and UCN3 (1 mM each) into the ARCN elicited similar decreases in MAP and HR. UCN1 was used as a prototype for the other experiments described below. HR responses elicited by UCN1 were significantly attenuated by bilateral vagotomy. Prior microinjections of NBI-27914 (CRF-1 receptor antagonist) and astressin (CRF-1 receptor and CRF-2 receptor antagonist) (1 mM each) into the ARCN significantly attenuated the cardiovascular responses elicited by UCN1 microinjections at the same site. Microinjections of UCN1 into the ARCN decreased efferent renal sympathetic nerve activity. It was concluded that microinjections of UCN1, UCN2, and UCN3 into the ARCN elicited decreases in MAP and HR. Decreases in MAP, HR, and renal sympathetic nerve activity elicited by UCN1 microinjections into the ARCN were mediated via CRF receptors. Bradycardic responses to UCN1 were mediated via the activation of vagus nerves, and decreases in MAP may be mediated via decreases in sympathetic nerve activity.

Neuroplasticity in the nucleus tractus solitarius precedes development of functional changes in autonomic regulation of arterial pressure in obese Zucker rats

Obese Zucker rats (OZR) develop elevated sympathetic nerve activity (SNA) and arterial pressure (AP) between 7–14 wks of age vs. lean Zucker rats (LZR). Baroreflexes are normal in juvenile OZR (7 wk), but impaired in adult OZR (12–14 wk). In adult OZR baroreceptor afferent nerves respond normally to rises in MAP, but direct stimulation of afferents evokes blunted decreases in SNA and MAP, suggesting changes in the brain impair baroreflexes. We examined if nucleus tractus solitarius (NTS), the brain site receiving baroreceptor inputs, is affected in adult OZR. Stimulation of NTS by microinjections of glutamate evoked comparable decreases in SNA and MAP in juvenile OZR vs. LZR, but reduced responses in adult OZR vs. LZR. However, stimulation the caudal ventrolateral medulla, a target of the NTS, evoked comparable decreases in SNA and MAP in adult OZR and LZR. We examined the time course of changes in NTS by expression of ΔFosB protein as a marker of neuroplasiticity. At 5 wks OZR and LZR had comparable ΔFosB+ neurons (203±30 vs. 195±22). However, by 7 wks NTS of OZR had more ΔFosB+ neurons than LZR (514.5±70 vs. 207±24.5; P = 0.027), which persisted at 12 wks (177±15.38 in OZR and 88±15.76 in LZR; P = 0.02). These data suggest reduced excitability of NTS neurons contributes to blunted baroreflexes in adult OZR. Furthermore, changes in the NTS occur prior to the onset of altered baseline SNA and MAP or NTS function. Funding: NIHHL086759.

Postexercise hypotension and sustained postexercise vasodilatation: what happens after we exercise?

A single bout of aerobic exercise produces a postexercise hypotension associated with a sustained postexercise vasodilatation of the previously exercised muscle. Work over the last few years has determined key pathways for the obligatory components of postexercise hypotension and sustained postexercise vasodilatation and points the way to possible benefits that may result from these robust responses. During the exercise recovery period, the combination of centrally mediated decreases in sympathetic nerve activity with a reduced signal transduction from sympathetic nerve activation into vasoconstriction, as well as local vasodilator mechanisms, contributes to the fall in arterial blood pressure seen after exercise. Important findings from recent studies include the recognition that skeletal muscle afferents may play a primary role in postexercise resetting of the baroreflex via discrete receptor changes within the nucleus tractus solitarii and that sustained postexercise vasodilatation of the previously active skeletal muscle is primarily the result of histamine H(1) and H(2) receptor activation. Future research directions include further exploration of the potential benefits of these changes in the longer term adaptations associated with exercise training, as well as investigation of how the recovery from exercise may provide windows of opportunity for targeted interventions in patients with hypertension and diabetes.

Sites of action of ghrelin receptor ligands in cardiovascular control

Circulating ghrelin reduces blood pressure, but the mechanism for this action is unknown. This study investigated whether ghrelin has direct vasodilator effects mediated through the growth hormone secretagogue receptor 1a (GHSR1a) and whether ghrelin reduces sympathetic nerve activity. Mice expressing enhanced green fluorescent protein under control of the promoter for growth hormone secretagogue receptor (GHSR) and RT-PCR were used to locate sites of receptor expression. Effects of ghrelin and the nonpeptide GHSR1a agonist capromorelin on rat arteries and on transmission in sympathetic ganglia were measured in vitro. In addition, rat blood pressure and sympathetic nerve activity responses to ghrelin were determined in vivo. In reporter mice, expression of GHSR was revealed at sites where it has been previously demonstrated (hypothalamic neurons, renal tubules, sympathetic preganglionic neurons) but not in any artery studied, including mesenteric, cerebral, and coronary arteries. In rat, RT-PCR detected GHSR1a mRNA expression in spinal cord and kidney but not in the aorta or in mesenteric arteries. Moreover, the aorta and mesenteric arteries from rats were not dilated by ghrelin or capromorelin at concentrations >100 times their EC(50) determined in cells transfected with human or rat GHSR1a. These agonists did not affect transmission from preganglionic sympathetic neurons that express GHSR1a. Intravenous application of ghrelin lowered blood pressure and decreased splanchnic nerve activity. It is concluded that the blood pressure reduction to ghrelin occurs concomitantly with a decrease in sympathetic nerve activity and is not caused by direct actions on blood vessels or by inhibition of transmission in sympathetic ganglia.