Changes In Sympathetic Nerve Activity Research Articles

Dynamic interactions between arterial pressure and sympathetic nerve activity: role of arterial baroreceptors.

The role of arterial baroreceptors in controlling arterial pressure (AP) variability through changes in sympathetic nerve activity was examined in conscious rats. AP and renal sympathetic nerve activity (RSNA) were measured continuously during 1-h periods in freely behaving rats that had been subjected to sinoaortic baroreceptor denervation (SAD) or a sham operation 2 wk before study (n = 10 in each group). Fast Fourier transform analysis revealed that chronic SAD did not alter high-frequency (0.75-5 Hz) respiratory-related oscillations of mean AP (MAP) and RSNA, decreased by approximately 50% spectral power of both variables in the midfrequency band (MF, 0.27-0.74 Hz) containing the so-called Mayer waves, and induced an eightfold increase in MAP power without altering RSNA power in the low-frequency band (0.005-0.27 Hz). In both groups of rats, coherence between RSNA and MAP was maximal in the MF band and was usually weak at lower frequencies. In SAD rats, the transfer function from RSNA to MAP showed the characteristics of a second-order low-pass filter containing a fixed time delay ( approximately 0.5 s). These results indicate that arterial baroreceptors are not involved in production of respiratory-related oscillations of RSNA but play a major role in the genesis of synchronous oscillations of MAP and RSNA at the frequency of Mayer waves. The weak coupling between slow fluctuations of RSNA and MAP in sham-operated and SAD rats points to the interference of noise sources unrelated to RSNA affecting MAP and of noise sources unrelated to MAP affecting RSNA.

Sympathetic nerve activity in hypotension and orthostatic intolerance.

The present paper reviews how changes in sympathetic nerve activity are related to hypotensive episodes and orthostatic intolerance in humans. It has been well documented that sympathetic neural traffic to skeletal muscles (muscle sympathetic nerve activity; MSNA) plays an essential role in maintaining blood pressure homeostasis mainly through baroreflex. The MSNA responded to gravitational loading from the head to the leg (+Gz) during passive head-up tilt (HUT). Patients who suffered from orthostatic hypotension with or without syncope were classified into at least two groups; low and high responders of MSNA to orthostatic loading. The typical examples belonging to the former group were patients of multiple system atrophy who had very low basal sympathetic outflow to muscle which responded extremely poorly to HUT. Patients of multiple system atrophy presented also postprandial hypotension in which muscle sympathetic response to oral glucose administration was absent. The latter group was represented by subjects who manifested vasovagal syncope with normal or even higher muscle sympathetic response to HUT, which was suddenly withdrawn concomitantly with bradycardia and hypotension. Similar withdrawal of sympathetic nerve traffic to muscle was encountered in a rare case of idiopathic non-orthostatic episodic hypotension which accompanied bradycardia. The MSNA was suppressed by short-term exposure to microgravity but was enhanced after long-term exposure to microgravity. Orthostatic intolerance after long-term exposure to microgravity was related to progressive reduction of muscle sympathetic response to orthostatic loading with impaired arterial baroreflex. It is concluded that hypotensive episodes are closely related to poor or lack of muscle sympathetic outflow, but may depend on various neural mechanisms to induce it.

Changes in sympathetic nerve activity of the mammalian ovary during a normal estrous cycle and in polycystic ovary syndrome: Studies on norepinephrine release.

Although it has been known for many years that the ovary is innervated by catecholaminergic nerve fibers and much experimental evidence has strengthened the notion that catecholamines are physiologically involved in the control of ovarian function, scarce evidence has been presented as to the role of sympathetic activity in ovarian pathologies that affect reproductive function. The purpose of this article is to provide a succinct overview of the findings in this area and discuss them relative to the pathology of polycystic ovary syndrome, the most common ovarian pathology in women during their reproductive years.

Analysis of sympathetic nerve activity in end-stage cardiomyopathy patients receiving left ventricular support

Background The left ventricular assist system (LVAS) has been used increasingly for patients with end-stage heart failure who are awaiting transplantation. Sympathetic nerve activity is known to correlate with cardiac function in chronic heart failure patients, but little is known about sympathetic nerve activity during LVAS support. In this study, we examined the status of sympathetic nerve activity in relation to mechanical support. Methods In this study, we included 10 consecutive patients with end-stage cardiomyopathy who were on LVAS support for at least 2 months (duration, 222 ± 59 days). None of these patients achieved enough functional recovery to be taken off LVAS. In these patients, we used iodine-125-metaiodobenzylguanidine ( 125I-MIBG) scintigraphy to examine the change of sympathetic nerve activity after LVAS implantation, and compared the results with the change of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) levels as well as with histologic optional findings. Samples for ANP and BNP measurement were obtained before and 30 days after LVAS implantation. Specimens for histologic analysis were obtained at the time of LVAS implantation and at the time of cardiac transplantation or autopsy. Results We observed marked decrease in serum levels of ANP and BNP 1 month after LVAS implantation. But myocardial sympathetic nerve function, which was evaluated with 125I-MIBG scintigraphy and expressed as the heart-to-mediastinum activity ratio, remained below normal even 2 months after the LVAS implantation (1.57 ± 0.19; normal, 2.34 ± 0.36). Serial histologic analysis in these 10 patients showed continuous increase in percentage of fibrosis and cell diameter despite ventricular unloading by the LVAS. Conclusions Sympathetic nerve function, which was evaluated on 125I-MIBG scintigraphy, did not improve during left ventricular support. Because none of the patients included in our study showed improvement in cardiac function or histologic findings, the recovery of myocardial sympathetic nerve function may be an important factor in myocardial recovery for cardiomyopathy patients on LVAS support.

Proceedings of the Australian Physiological and Pharmacological Society Symposium: The Hypothalamus HYPOTHALAMIC PARAVENTRICULAR NUCLEUS AND CARDIOVASCULAR REGULATION

1. The hypothalamic paraventricular nucleus (PVN) is an important integrative site within the brain composed of magnocellular and parvocellular neurons. It is known to influence sympathetic nerve activity. 2. The parvocellular PVN contains neurons that project to the intermediolateral cell column of the thoraco-lumbar spinal cord (IML). This defines the PVN as an autonomic 'premotor nucleus', one of only five present within the brain. 3. Another projection arising from the PVN is a prominent innervation of the pressor region of the rostral ventrolateral medulla (RVLM), also a premotor nucleus. The distribution of the PVN neurons projecting to the RVLM is similar to that of the PVN neurons that project to the IML. 4. It has been found that up to 30% of spinally projecting neurons in the PVN also send collaterals to the RVLM. Thus, there are neurons in the PVN that can: (i) directly influence sympathetic nerve activity (via PVN-IML connections); (ii) indirectly influence sympathetic nerve activity (via PVN-RVLM connections); and (iii) both directly and indirectly influence sympathetic nerve activity (via neurons with collaterals to the IML and RVLM). 5. In the rat, results of studies using the protein Fos to identify activated neurons in the brain suggest that neurons in the PVN with projections to the IML or RVLM may be activated by decreases in blood volume. 6. In conclusion, the PVN can influence sympathetic nerve activity. Within the PVN are neurons with anatomical connections that enable them to affect sympathetic nerve activity either directly, indirectly or via both mechanisms (via collaterals). Studies that have examined the role of specific subgroups within the PVN suggest that PVN neurons with connections to the IML or to the RVLM may play a role in the reflex changes in sympathetic nerve activity that are involved in blood volume regulation.

Isometric handgrip training reduces arterial pressure at rest without changes in sympathetic nerve activity.

The purpose of this study was to determine whether isometric handgrip (IHG) training reduces arterial pressure and whether reductions in muscle sympathetic nerve activity (MSNA) mediate this drop in arterial pressure. Normotensive subjects were assigned to training (n = 9), sham training (n = 7), or control (n = 8) groups. The training protocol consisted of four 3-min bouts of IHG exercise at 30% of maximal voluntary contraction (MVC) separated by 5-min rest periods. Training was performed four times per week for 5 wk. Subjects' resting arterial pressure and heart rate were measured three times on 3 consecutive days before and after training, with resting MSNA (peroneal nerve) recorded on the third day. Additionally, subjects performed IHG exercise at 30% of MVC to fatigue followed by muscle ischemia. In the trained group, resting diastolic (67 +/- 1 to 62 +/- 1 mmHg) and mean arterial pressure (86 +/- 1 to 82 +/- 1 mmHg) significantly decreased, whereas systolic arterial pressure (116 +/- 3 to 113 +/- 2 mmHg), heart rate (67 +/- 4 to 66 +/- 4 beats/min), and MSNA (14 +/- 2 to 15 +/- 2 bursts/min) did not significantly change following training. MSNA and cardiovascular responses to exercise and postexercise muscle ischemia were unchanged by training. There were no significant changes in any variables for the sham training and control groups. The results indicate that IHG training is an effective nonpharmacological intervention in lowering arterial pressure.

Increased sympathetic activity after atrioventricular junction ablation in patients with chronic atrial fibrillation

OBJECTIVESThe aim of this study was to determine the changes in sympathetic nerve activity (SNA) after atrioventricular junction (AVJ) ablation in patients with chronic atrial fibrillation (AF).BACKGROUNDPolymorphic ventricular tachycardia (PMVT) has been reported after AVJ ablation in patients paced at a rate of ≤70 beats/min. We hypothesized that AVJ ablation results in sympathetic neural changes that favor the occurrence of PMVT and that pacing at 90 beats/min attenuates these changes.METHODSSympathetic nerve activity, 90% monophasic cardiac action potential duration (APD90), right ventricular effective refractory period (ERP) and blood pressure measurements were obtained in 10 patients undergoing AVJ ablation. Sympathetic nerve activity was analyzed at baseline and during and after successful AVJ ablation for at least 10 min. Data were also collected after ablation at pacing rates of 60 and 90 beats/min. The APD90 and ERP were measured before and after AV block during pacing at 120 beats/min.RESULTSSympathetic nerve activity increased to 134 ± 16% of the pre-ablation baseline value (p < 0.01) after successful AVJ ablation plus pacing at 60 beats/min and decreased to 74 ± 8% of baseline (p < 0.05) with subsequent pacing at 90 beats/min. Both APD90 and ERP increased significantly.CONCLUSIONS1) Ablation of the AVJ followed by pacing at 60 beats/min is associated with an increase in SNA. 2) Pacing at 90 beats/min decreases SNA to or below the pre-ablation baseline value. 3) Cardiac APD and ERP increase after AVJ ablation. The increase in SNA, along with the prolongation in APD, may play a role in the pathogenesis of ventricular arrhythmias that occur after AVJ ablation.

Sodium sensitivity and sympathetic nervous system in hypertension induced by long-term nitric oxide blockade in rats.

1. Pharmacological inhibition of nitric oxide (NO) synthesis is known to produce acute and chronic hypertension in many animal species, but the underlying mechanisms mediating the hypertension are not completely understood. In particular, the pathogenetic roles of sodium sensitivity and the sympathetic nervous system in this model of hypertension are controversial. The present study was designed to test the hypothesis that long-term administration of the NO synthesis inhibitor NG-nitro-L-arginine methyl ester (L-NAME) to male Sprague-Dawley rats would produce a sodium-sensitive hypertension and that the enhanced activity of the sympathetic nervous system in this type of hypertension contributes to the sodium sensitivity. 2. NG-Nitro-L-arginine methyl ester was added to drinking fluid for 8 weeks at a concentration of 16 mg/dL. Rats received tap water for the first 4 weeks of the study and were then divided into two groups and placed on either a normal or high sodium intake (ingestion of either tap water or 0.9% NaCl, respectively). Awake systolic blood pressure was measured by the tail-cuff method every week. Urinary excretion rates of the stable NO metabolites and catecholamines during NO synthesis inhibition were examined. 3. Long-term administration of L-NAME produced a marked and sustained elevation in arterial pressure without altering urine flow, or sodium excretion rate. NG-Nitro-L-arginine methyl ester-induced hypertension was accompanied by a decreased urinary excretion of the stable NO metabolites NO2- and NO3- and was aggravated when rats drank 0.9% NaCl in place of tap water. Urinary excretion of adrenaline and noradrenaline, but not dopamine, in L-NAME-treated rats increased significantly within the first week of the study compared with control rats. L-Arginine (2 g/dL in drinking fluid) completely reversed the elevation of arterial pressure as well as the decrease in urinary NO2- and NO3- excretion and the increased urinary excretion of catecholamines associated with L-NAME treatment by 3 weeks of concomitant administration. 4. These results suggest that long-term inhibition of NO synthesis produces a sodium-sensitive hypertension and that changes in sympathetic nerve activity may, at least in part, contribute to the sodium sensitivity in this type of hypertension.

Visceral afferent activation-induced changes in sympathetic nerve activity and baroreflex sensitivity.

The following experiments were done to determine whether changes in baroreflex sensitivity evoked by cervical vagus nerve stimulation are due to sympathoexcitation mediated by the parabrachial nucleus. The relative contribution of cardiopulmonary and general gastric afferents within the cervical vagus nerve to the depression in baroreflex sensitivity are also investigated. Male Sprague-Dawley rats anesthetized with thiobutabarbital sodium (50 mg/kg) were instrumented to measure blood pressure and heart rate or for the continuous monitoring of renal sympathetic nerve activity. Baroreflex sensitivity was measured using bolus injections of phenylephrine. Electrical stimulation of the cervical vagus (with or without the aortic depressor nerve) or the abdominal vagus nerve produced a significant increase in renal nerve activity and a decrease in baroreflex sensitivity. Both of these effects were blocked after the microinjection of lidocaine into the parabrachial nucleus before nerve stimulation. Therefore, we conclude that an increase in the activity of cardiac, pulmonary, or general gastric afferents mediated the increased sympathetic output and decreased baroreflex sensitivity via a pathway involving the parabrachial nucleus.

Related changes in sympathetic activity, cerebral blood flow and intracranial pressure, and effect of an alpha-blocker in experimental subarachnoid haemorrhage.

We investigated the changes in sympathetic nerve activity (SNA) and cerebral blood flow (CBF) with or without increase in intracranial pressure (ICP) in the acute stage of experimental subarachnoid haemorrhage (SAH). ICP was increased or controlled by rapid or slow injection of blood and saline, and the effect of an alpha-blocker, phentolamine, was also investigated in each condition. Following marked increase in ICP induced by rapid injection of blood or saline, increase in intracranial and general SNA and decrease in CBF were observed. Both changes were significantly decreased in magnitude by prior administration of phentolamine. When increase in ICP was not induced, by slow injection of blood, both SNA and CBF decreased, and these changes were alleviated by phentolamine. However, when increase in ICP was not induced by saline, neither SNA nor CBF significantly changed. These findings suggest that marked increase in ICP is the primary cause of the pathological changes occurring immediately after SAH, and that the decrease in CBF in mild SAH without increase in ICP is caused by blood itself. Administration of an alpha-blocker may be effective in improving the abnormal sympathetic nervous system induced by marked increase in ICP.

GABA-mediated inhibition of raphe pallidus neurons regulates sympathetic outflow to brown adipose tissue.

Sympathetic nerve activity to brown adipose tissue (BAT) regulates adipocyte metabolism of its stored lipid fuel and thus the thermogenesis in BAT. To determine if the discharge of neurons in the rostral raphe pallidus (RPa) can influence BAT thermogenesis, changes in sympathetic nerve activity to BAT were recorded after microinjection (60 nl) of the GABAA receptor antagonist bicuculline (500 microM) into the RPa in chloralose-urethan-anesthetized, ventilated rats. Bicuculline caused a large, rapid rise in the sympathetic nerve activity to BAT (which had also increased during acute hypothermia) from very low, normothermic control levels to maximum values (mean: 1,949 +/- 604% control; n = 13) after 4-6 min. The sympathetic nerve discharge to BAT had a mean burst frequency (3. 5 +/- 0.3 Hz) that was significantly less than the heart rate (7.3 +/- 0.2 beats/min), and it was not inhibited during baroreceptor reflex activation. Bicuculline-stimulated increases in the sympathetic nerve activity to BAT and cold-evoked increases in neuronal fos expression were localized to the RPa at the level of the caudal half of the facial nucleus. This dramatic increase in sympathetic nerve activity to BAT after disinhibition of neurons in rostral RPa is consistent with a major role for RPa neurons, perhaps as sympathetic premotoneurons for BAT, in medullary control of BAT thermogenesis.

The effects of ketamine and propofol on neuronal nicotinic acetylcholine receptors and P2x purinoceptors in PC12 cells.

We studied the effects of ketamine and propofol on two ligand-gated ion channels mediating fast synaptic transmission through sympathetic ganglia, neuronal nicotinic acetylcholine receptors (nAchRs), and P2X purinoceptors in a rat pheochromocytoma cell line PC12 using whole cell voltage clamp recording. Ketamine and propofol similarly inhibited the nicotine-induced inward current reversibly and dose-dependently at the membrane potential of -60 mV but had no effects on the adenosine triphosphate-induced current. Both anesthetics accelerated the current decay during agonist application, resulting in greater inhibition on the steady current than the peak current. The 50% inhibition concentration values for the steady current were lower than the clinically relevant concentrations for ketamine (2.8+/-0.6 microM) and higher than those for propofol (5.4+/-0.6 microM). Both anesthetics induced an addition of the fast component to the decay phase and an acceleration of the slow component, which suggests an open channel blockade or an enhancement of desensitization as a mechanism. The effects on closed channels seemed to be small because preincubation with the anesthetics did not significantly augment the block. Inhibition was voltage-independent at membrane potentials between -20 and -70 mV and was consistent with a noncompetitive block. Inhibition of the neuronal nAchR-mediated current may lead to the suppression of synaptic transmission in sympathetic ganglia by ketamine, but not by propofol, at the clinically relevant concentrations. However, these results are not consistent with changes in sympathetic nerve activities reported for animals or humans anesthetized with ketamine or propofol, which suggests effects from other systems, such as the central nervous system in vivo. Ketamine (at smaller than clinically relevant concentrations) and propofol (at larger than clinically relevant concentrations) inhibited neuronal nicotinic acetylcholine receptor-mediated current in PC12 cells, which possess the receptors that resemble those in postganglionic sympathetic neurons. These findings are not consistent with in vivo experiments, which suggests that effects from other systems, such as the central nervous system, are of importance.

Effects of dynamic leg exercise on subcutaneous blood flow rate in the lower limb of man.

Subcutaneous blood flow (SBF) was studied simultaneously in the upper arm at heart level and in the lower limb during positional changes and during leg exercise in seven healthy males. SBF was estimated by local clearance of 133Xenon registered by portable cadmium telluride detectors. Venous pressure was recorded directly on dorsum on the foot. Changing the position from supine to head-up tilt, SBF decreased by 43% (P less than 0.01) at the arm level, 40% at the thigh (P less than 0.01), 47% at the calf (P less than 0.01) and decreased by 51% at the ankle level (P less than 0.01). Performing 20 heel-raisings per min in nearly erect posture, SBF increased by 96% at the thigh (P less than 0.01), 25% at the calf (P greater than 0.1) and increased by 18% at the ankle level (P greater than 0.01). At 40 heel-raisings per min SBF increased by 99% at the thigh (P less than 0.01), 121% at the calf (P less than 0.01), but only 44% at the ankle level (P greater than 0.1). During leg exercise subcutaneous vascular resistance was significantly increased at arm and ankle levels. In contrast, a vasodilatory response was noticed at the thigh and calf levels and seemed associated with a decrease in local venous pressure to below the trigger level of the sympathetic veno-arteriolar reflex mechanism. In conclusion, SBF in the lower limb of man was increased during exercise. The increase in SBF could only partly be ascribed to the concomitant increase in perfusion pressure. The local blood flow response seemed modified by changes in sympathetic nervous activity and metabolic rate.

Blood mobilization from the liver of the anaesthetized dog.

The abdominal circulation contains a high proportion of the total blood volume and this can change either passively in response to changes in vascular distending pressure or actively (termed a capacitance response) to changes in sympathetic nervous activity. The liver is the largest abdominal organ and this study was designed to evaluate its potential contribution to overall vascular capacitance and compliance. In chloralose anaesthetized dogs, the liver was vascularly isolated, perfused through the portal vein and hepatic artery at either constant pressures or constant flows and drained from the hepatic veins at constant pressure. Changes in vascular resistance were assessed from changes in inflow pressures or flows and hepatic blood volume was determined by differences between net inflow and outflow. During constant flow perfusion the change in hepatic volume (capacitance change) in response to supramaximal stimulation of sympathetic nerves at 16 Hz was (mean +/- S.E.M.) -2.40 +/- 0.61 ml (kg body weight)-1. This response was not significantly different during constant pressure perfusion. The changes in portal venous and hepatic arterial pressures during stimulation at constant flow perfusion were +0.67 +/- 0.13 and +4.92 +/- 0.67 kPa, respectively. The compliance of the liver, assessed as the change in volume to a change in hepatic venous pressure, was +5.44 +/- 0.18 ml kg-1 kPa-1. These results indicate that the liver has a major capacitance role, comparable to that of the canine spleen and, in addition, is highly compliant. No evidence was found to suggest that a sphincter on the hepatic outflow exists. Assuming similar responses occur in humans, who do not possess a large contractile spleen, the liver would be the most important controllable blood reservoir in the body.

Physical activity, skeletal muscle beta-adrenoceptor changes and oxidative metabolism in experimental chronic heart failure.

In chronic heart failure (CHF), changes in sympathetic nervous activity and skeletal muscle metabolism contribute to a limitation in the capacity for exercise. The aim of this study was to investigate the potential relationships between physical deconditioning, skeletal muscle beta-adrenoceptor (beta-AR) characteristics and muscle metabolic changes in rats with coronary ligation-induced experimental CHF. Muscle beta-AR and norepinephrine levels were assessed in rats with CHF that had been treated with propranolol at 28 mg/kg/day and compared with rats with CHF that had not been treated and those that had undergone sham operations. The soleus muscle was investigated because of its predominantly oxidative fibre-type composition. Measurements of spontaneous locomotion activity were carried out using telemetry. After 85 days, muscle energetic phosphate levels were assessed using 31P-magnetic resonance spectroscopy. The phosphocreatine resynthesis rate was decreased in the untreated CHF rats (15 +/- 3 vs 33 +/- 5 mmol L-1 min-1 in the sham-operated rats, p < 0.05), but this had been partially reversed in the rats given propranolol (22 +/- 3 mmol L-1 min-1, non-significant (NS) when compared with the sham-operated rats). Spontaneous activity did not differ among the three groups of animals. Soleus beta-adrenoceptor density was decreased in rats with CHF (8.8 +/- 3.0 fM/mg of protein vs 22.0 +/- 7.0 fM/mg of protein in the sham-operated rats, p < 0.05) and normalized in the propranolol-treated rats (31.9 +/- 7.0 fM/mg of protein, NS vs the sham-operated rats; p < 0.05 vs the untreated rats with CHF). Unchanged spontaneous activity in the rats with CHF suggests that physical deconditioning could not account for the muscle metabolic changes. Changes in skeletal muscle energy metabolism were accompanied by changes in beta-AR density, occurring in typically oxidative beta-AR-rich muscles, reversible after beta-blocker therapy and therefore suggestive of beta-AR downregulation.

Gene Transcription and Synthesis of Adrenomedullin by Cultured Human Renal Cells

Adrenomedullin (ADM) is a novel 52 amino acid peptide with a potent vasodilator effect. Gene expression of ADM is found in human kidney but the exact cell source in the kidney is uncertain. Its plasma level is raised in association with changes in sympathetic nervous activity and body fluid volume in hypertension and chronic renal failure. Herein, we examined the presence of mRNA encoding for ADM in cultured human glomerular cells. Adrenomedullin in cell culture supernatant was measured by a radio-immunoassay (with a detection level of 3.2 pmol/l). Adrenomedullin mRNA was found in cultured mesangial and glomerular epithelial cells as well as in vascular endothelial cells. Supernatant levels of ADM for cultured mesangial and glomerular epithelial cells were 21.2 and < 3.2 pmol/l respectively. Contrary to vascular smooth muscle cells, the gene expression for ADM in mesangial cells was up-regulated when incubated with increasing concentration of TNF-α or fetal bovine serum (FBS) but this effect was not observed with very high concentration. Parallel results were observed in adrenomedullin levels in supernatant from mesangial cell cultures. Forskolin, captopril, or TGF-β had no effect on the transcription or synthesis of ADM in mesangial cells. The gene expression for ADM in glomerular epithelial cells was down-regulated when incubated with increasing concentration of TNF-α, forskolin or FBS. The ADM levels in all supernatant from resting glomerular epithelial cell cultures were < 3.2 pmol/l. Recent murine data show that ADM stimulates the release of cAMP but suppresses mitogenesis in cultured mesangial cells. Our results suggest ADM is synthesized by mesangial cells in an autocrine fashion and the peptide may potentially be involved in intra-renal blood pressure control.

Inhibition of NO synthesis does not potentiate dynamic cardiovascular response to sympathetic nerve activity.

We examined whether the inhibition of nitric oxide (NO) synthesis potentiates the dynamic sympathetic regulation of the cardiovascular system through the baroreflex. In anesthetized rabbits, we imposed random pressure perturbations on the isolated carotid sinuses to evoke random changes in sympathetic nerve activity (SNA). We estimated the transfer functions from SNA to both aortic pressure (AoP) and heart rate (HR). The inhibition of NO synthesis by NG-monomethyl-L-arginine (L-NMMA, 40 mg/ kg) altered neither the transfer function from SNA to AoP nor that from SNA to HR. In contrast, sodium nitroprusside (3-6 micrograms.kg-1.min-1) significantly decreased the steady-state gain (40.3 +/- 11.7% of the control, P < 0.05) of the transfer function from SNA to AoP without affecting the HR responses. We conclude that the basal release of NO may have a role in the tonic blood pressure regulation, whereas it may not be involved in the dynamic sympathetic regulation of AoP or HR through the baroreflex.

Stimulation of gastric osmoreceptors but not the sodium monitor increases renal angiotensin-converting enzyme activity.

1. Stimulation of the gastric sodium monitor has been reported to cause a decrease in renal nerve activity and also a decrease in plasma renin activity in renal venous blood. This suggests that changes in sympathetic nerve activity and in the intrarenal renin-angiotensin system may mediate the natriuresis that occurs following gastric sodium administration. In the present study we sought to determine whether gastric sodium administration also modulates angiotensin-converting enzyme (ACE) activity in the kidney. 2. Male Sprague-Dawley rats were equilibrated on a low-sodium (0.008%) diet for 7 days. On the day of the experiment, rats were anaesthetized and kidneys were harvested and immediately snap frozen at 0 and 60 min after intragastric administration of a saline load (1.5 mmol/kg as 3 mol/L saline) or an equivalent volume of iso-osmotic urea (5.95%). Angiotensin-converting enzyme activity was determined by incubation of kidney homogenates with hippuryl-histidyl-leucine and fluorometric assay of the histidyl-leucine generated. 3. Angiotensin-converting enzyme activity in the kidney increased in response to the intragastric administration of both sodium chloride and urea. Angiotensin-converting enzyme activity increased significantly from control levels (189.9 +/- 24.3 nmol/min per g protein) by 60 min in both NaCl-and urea-treated groups (492.3 +/- 27.3 and 468.6 +/- 28.7 nmol/min per g protein, respectively; P < 0.0005). 4. We conclude that instillation of sodium chloride or isoosmotic urea into the stomach increase ACE activity in the kidney. The results of the present study suggest that this effect is due to changes in osmolality rather than stimulation of the gastric sodium monitor.

Nerve-mediated antidiuresis and antinatriuresis after air-jet stress is modulated by angiotensin II.

A putative interaction between angiotensin II (Ang II) and the sympathetic nervous system within the kidney has been reported. We tested the hypothesis in conscious rats that endogenous Ang II modulates the renal effects of a stress-induced increase in sympathetic nerve activity. We recorded mean arterial blood pressure, heart rate, renal sympathetic nerve activity, renal hemodynamics, urine volume, and urinary sodium content in conscious rats. We used the Ang II type 1 receptor blocker ZD 7155 to inhibit the effects of endogenous Ang II. Ten minutes of air-jet stress increased renal sympathetic nerve activity by 98 +/- 4% (n = 6) without changing systemic hemodynamics. Air-jet stress reduced urine volume (from 31 +/- 3 to 8 +/- 4 microL/min per gram kidney weight, P < .05, n = 12) and sodium excretion (from 4.3 +/- 0.9 to 1.2 +/- 0.3 mumol/min per gram kidney weight, P < .05, n = 12). After renal denervation, air-jet stress had no effect on either parameter. Six micrograms of the Ang II type 1 receptor inhibitor ZD 7155 blunted the decrease in urine volume and sodium excretion in response to air-jet stress, although the increase in renal sympathetic nerve activity during air-jet stress and the pressor response to exogenous Ang II were not affected. Glomerular filtration rate and renal plasma flow were also not affected. Higher doses of 30 and 60 micrograms ZD 7155 inhibited the pressor response to exogenous Ang II and abolished the changes in urine volume and sodium excretion in response to air-jet stress. None of the ZD 7155 doses affected urinary sodium excretion permanently. Hence, the Ang II type 1 receptor antagonist ZD 7155 impaired or abolished the renal nerve-mediated antinatriuresis and anitidiuresis in response to air-jet stress. We conclude that endogenous Ang II modulates the renal effects of centrally mediated changes of sympathetic nerve activity in conscious rats.

Changes in tissue blood flow and sympathetic activities to various organs during prolonged hemorrhagic hypotension in monkeys

This experiment was designed to determine whether prolonged hemorrhagic hypotension in anesthetized monkeys produces differential control of tissue blood flow and sympathetic nerve activities to various organs (heart, kidney, liver, spleen, and hind-limb). We performed simultaneous multifiber recording of sympathetic nerve activity to the kidney (RNA), heart (CNA), spleen (SpNA), liver (HNA), and hind-limb (LNA) during sustained hemorrhagic hypotension at a mean blood pressure of 40 mmHg for 2 h. Immediately after bleeding, all of the sympathetic nerve activities increased significantly (Stage I) and then gradually decreased towards the prebleeding levels (Stage II). Thereafter, the secondary sympathetic excitation was observed (Stage III), followed by a gradual decrease in sympathetic activities below the prebleeding levels (Stage IV). The shed blood started to return to the animals at this final stage. Time course of changes in sympathetic nerve activities did not differ among organs innervated. However, tissue blood flow of the renal cortex, liver, skeletal muscle and spleen significantly decreased at Stage I and remained at low levels until the end of the experimental period. In contrast, blood flow of the renal medulla and heart was preserved until Stage III and Stage IV, respectively. These results indicate that although the sympathetic response to prolonged hemorrhagic hypotension of 40 mmHg did not differ among organs, changes in tissue blood flow were variable and blood flow to the heart and renal medulla was maintained at a steady level until a late stage of hemorrhage.