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Examines the effect of paraventricular nucleus (PVN) GABAa receptor antagonism on sympathetic nerve discharge (SND) frequency components in alpha-chloralose-anesthetized rats. Alterations of the frequency components in the sympathetic nerves; Autospectral and coherence analyses of renal and splenic SND.

Investigates the effects of end-tidal carbon dioxide pressure (PETCO2) on muscle sympathetic nerve activity. Influence of PETCO2 levels on MSNA response to HUT and orthostatic stress; Testing of the hypothesis that hypocapnia may be detrimental to increases in MSNA and total peripheral resistance during head-up tilt.

Studies tonic sympathetic support of resting metabolic rate (RMR) in human adults. Evidence that complete beta adrenergic blockade was achieved; Changes in RMR during saline and propranolol infusions; Relations between sympathetic nervous system beta-adrenergic support of RMR and plasma catecholamine concentrations.

Tests the hypothesis that arachidonic acid both inhibits and enhances whole cell calcium currents in rat sympathetic neurons. Concentration dependence and reversibility of whole cell barium current inhibition by arachidonic acid; Summary of the effects of other fatty acids on tail currents.

Tests the hypothesis that vascular cells promote the survival of postganglionic sympathetic neurons in the absence of nerve growth factor. Influence of endothelin on the survival of postganglionic sympathetic neurons in neuronal vascular smooth muscle (VSM) cocultures; Ability of VSM-derived factors to modulate neuronal survival.

Tests the hypothesis that different adrenal sympathetic preganglionic neurons (SPN) regulate epinephrine and norepinephrine secretion. Antidromic identification of adrenal SPN; Rostral ventrolateral medulla-evoked discharge of adrenal SPN; Baroreceptor reflex influences on the discharge of adrenal SPN.

Studies aging and baroreflex control of renal sympathetic nerve activity (RSNA) and heart rate in rats. Spontaneous and reflex changes in baroreflex control; Influence of nitroprusside and phenylephrine on baroreflex control of heart rate in rats; Vagal and sympathetic function in aging rats.

Studies sympathetic activity in early renal posttransplantation hypertension in rats. Adrenal tyrosine hydroxylase mRNA content; Responses of mean arterial pressure, heart rate, and mean integrated sympathetic nerve activity to cumulative intracerebroventricular administration of guanabenz.

Studies the interaction of the vestibular system and baroreflexes on sympathetic nerve activity in humans. Cardiovascular responses to lower body negative pressure with head-down rotation; Changes in sympathetic muscle nerve activity (MSNA); Absolute mean increase in MSNA.

Studies the effect of baroreceptor denervation and heart failure on the chaotic behavior of renal sympathetic nerve activity. Effect of sinoaortic and cardiac baroreceptor denervation in normal rats; Association between chronic heart failure and impaired sinoaortic and cardiac baroreceptor function.

Reveals that changes in sympathetic or vagal tone in rabbits can alter the dynamic heart rate response to stimulation of the other nerve. Sigmoidal relationship between the linearly predicted and the measured heart rates; Stimulation of nerves using large-amplitude Gaussian white noise.

Determines the effect of caloric vestibular stimulation on sympathetic outflow to skin (SSNA). Comparison with effect on sympathetic outflow to muscle; Difference between SSNA responses to caloric vestibular stimulation and motion sickness.

Presents evidence linking nitric oxide to the suppression of sympathetic vasoconstriction in the mesentery and kidney at the spinal level. Mediation of hindquarter tone at supraspinal and synaptic levels; Effect of the alpha1-receptor blockade, prazosin, on hindquarter resistance.

Studies the impaired downregulation of alpha-adrenergic responsiveness, despite a comparable level of sympathetic nervous system (SNS) activity, which contributed to high blood pressure in older hypertensive humans. Measurement of the arterial plasma norepinephrine (NE) levels and extravascular NE release rate; Implication of greater SNS activity.

Discusses the role of sympathetic nerve activity reductions in postexercise hypotension. Significance of postexercise hypotension in hypertensive individuals; Effect of exercise on mean arterial pressure; Response of myocardial contractility to exercise.

Compares the whole body and regional norepinephrine (NE) kinetics between lean amd obese women. Physiology of sympathetic nervous system (SNS); Materials and methods; Results of the experiments; Discussion on the results of the study.

Provides information on a study investigating the relationships between sympathetic nervous system (SNS) activity, as indicated by catecholamines, and the end-organ effect of the SNS on the heart. Methodology used to conduct the study; Information on the spontaneous baroreflex slope; Findings of the study.

Studies the characteristics of renal sympathetic nerve activity in sodium-retaining disorders. Steady-state averaging; Power spectrum analysis; Sympathetic peak detection.

Investigates the effects of pulsatile and nonpulsatile systemic circulation on the sympathetic nerve activity in anesthetized goats. Discharge pattern of RNA during native and artificial pulsatile circulation and during artificial nonpulsatile circulation; Significance of pulsation in circulatory regulation.

Reports on baroreceptor-induced inhibition of sympathetic neurons by GABA acting at a spinal site. Surgical preparation; Experimental protocol; Spinal nature of test response; Drug administration; Histology; Statistical analysis.

Investigates whether nitric oxide (NO) synthase inhibition modulates basal sympathetic nerve discharge (SND) in baroreceptor-innervated and -denervated, chloralose-anesthetized Sprague-Dawley rats. Indication that NO synthase inhibition can produce nonuniform changes in SND in baroreceptor-denervated rats.

Investigates the effect of central administration of prostaglandin E2 (PGE2) and its selective agonists on splenic sympathetic nerve activity (SNA) were investigated in anesthesized rats. Indication that brain PGE2 increases splenic SNA.

Presents a study that attempts to elucidate the influence of arginine vasopressin (AVP) in the nucleus tractus solitarius (NTS) on baroreflex control of mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) in urethan-anesthesized rats. Indication that endogenous AVP within the NTS contributes to cardiovascular regulation.

Presents a study that identify pulse phasic activity in nucleus tractus solitarius (NTS) neurons in the anesthesized rabbit. Indication that many NTS neurons do have pulse phasic activity consistent with baroreceptor input; Identifying whether the NTS neurons responsive to baroreceptor inputs had spontaneous activity with sympathetic output; Brain stem.

Studies the sudden cardiac death characteristics of fluctuations of arterial pressure, cardiac rhythm and probably sympathetic nerve activity in seven patients undergoing clinical electrophysiological testing. Sympathetic responses to ventricular dysrhythmias; Relation to baseline sympathetic activity; Potential relevance to sudden cardiac death.

Presents an experimental study on in-phase cardiac and renal sympathetic discharges. Baroreceptor reflexes; Model of multiple and dynamically coupled brain stem generators of cardiac-related rhythm; Sympathetic nerve discharge (SND).

Presents a study to examine changes in central and peripheral hemodynamics in humans. Muscle sympathetic nerve activity (MNSA) during graded head-down tilt (HDT); Cardiopulmonary baroreceptors; Central venous pressure; Thoracic impedance; Sympathetic nerve activity; Forearm vascular resistance; Total peripheral resistance.

Presents a study on the effects of vena caval occlusion-induced systemic hypotension of 50 mmHg lasting min (VCO) on efferent sympathetic nerve activity (SNA) and sympathetic baroreflex responsiveness. Experimental preparation; Recording and quantification of SNA to the heart, kidney, liver and spleen; Experimental protocols; Baroreflex sensitivity.

Studies the catecholaminergic innervation of white adipose tissue in Siberian hamsters. Possible differential sympathetic neural control over catecholamine-induced lipolysis; Anatomy and neurochemistry; Labeling of neurons in the sympathetic nervous system.

Characterizes the maturation of cardiopulmonary reflex control of renal sympathetic nerve activity (RSNA) independent of influences from the arterial baroreflex. Sinoaortic denervation (SAD); Increase of right atrial pressure; Blockage of reflex bradycardia seen with volume expansion in newborn lambs by SAD.

Examines the effects of electrical and chemical stimulation of the area postrema (AP) on mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) in urethran- and sodium-anesthetized rats and unanesthetized decerebrate rats. Mediation of peripheral responses to L-glutamate and electrical stimulation of the AP over different pathways.

Examines alterations of synaptic transmission in sympathetic ganglia of spontaneously hypertensive rats. Tissue preparation; Synaptic potentials and currents; Current-voltage relationships; Presynaptic transmitter release and postsynaptic sensitivity; Repetitive synaptic activation.

Studies the interaction of sympathetic nerve activity (SNA) with blood pressure (BP) and heart rate (HR) in conscious rats. Digital reconstruction of SNA, mean arterial pressure (MAP), HR and respiration; Reduction of variability of parameters.

Examines the changes in ovine renal sympathetic nerve activity and baroreflex function at birth. Arterial blood gas (ABG) values in control and enalapril-treated animals; Effects of angiotensin converting enzyme inhibition on systemic hemodynamics and baroreflex responses after birth.

The effect of cardiovascular deconditioning on central nervous system processing of baroreceptor afferent activity was evaluated following 14 days of hindlimb unloading (HU). Inactin-anesthetized rats were instrumented with catheters, renal sympathetic nerve electrodes, and aortic depressor nerve electrodes for measurement of mean arterial pressure, heart rate, renal sympathetic nerve activity (RSNA), and aortic depressor nerve activity (ADNA). Baroreceptor and baroreflex functions were assessed during infusion of phenylephrine and sodium nitroprusside. Central processing of baroreceptor afferent input was evaluated by linear regression relating RSNA to ADNA. The maximum baroreflex-elicited increase in RSNA was significantly reduced in HU rats (122 +/- 3.8 vs. 144 +/- 4.9% of baseline RSNA), whereas ADNA was not altered. The slope (-0.18 +/- 0.04 vs. -0.40 +/- 0.04) and y-intercept (121 +/- 3.2 vs. 146 +/- 4.3) of the linear regression relating increases in efferent RSNA to decreases in afferent ADNA during hypotension were significantly reduced in HU rats. There were no differences during increases in arterial pressure. Results demonstrate that the attenuation in baroreflex-mediated increases in RSNA following HU is due to changes in central processing of baroreceptor afferent information rather than aortic baroreceptor function.

Whole body heating decreases central venous pressure (CVP) while increasing muscle sympathetic nerve activity (MSNA). In normothermia, similar decreases in CVP elevate MSNA, presumably via cardiopulmonary baroreceptor unloading. The purpose of this project was to identify whether increases in MSNA during whole body heating could be attributed to cardiopulmonary baroreceptor unloading coincident with the thermal challenge. Seven subjects were exposed to whole body heating while sublingual temperature, skin blood flow, heart rate, arterial blood pressure, and MSNA were monitored. During the heat stress, 15 ml/kg warmed saline was infused intravenously over 7-10 min to increase CVP and load the cardiopulmonary baroreceptors. We reported previously that this amount of saline was sufficient to return CVP to pre-heat stress levels. Whole body heating increased MSNA from 25 +/- 3 to 39 +/- 3 bursts/min (P < 0. 05). Central blood volume expansion via rapid saline infusion did not significantly decrease MSNA (44 +/- 4 bursts/min, P > 0.05 relative to heat stress period) and did not alter mean arterial blood pressure (MAP) or pulse pressure. To identify whether arterial baroreceptor loading decreases MSNA during heat stress, in a separate protocol MAP was elevated via steady-state infusion of phenylephrine during whole body heating. Increasing MAP from 82 +/- 3 to 93 +/- 4 mmHg (P < 0.05) caused MSNA to decrease from 36 +/- 3 to 15 +/- 4 bursts/min (P < 0.05). These data suggest that cardiopulmonary baroreceptor unloading during passive heating is not the primary mechanism resulting in elevations in MSNA. Moreover, arterial baroreceptors remain capable of modulating MSNA during heat stress.

The contribution of carotid chemoreceptors to hypercapnia-induced mesenteric venoconstriction was examined in 12 alpha-chloralose-anesthetized rabbits (1.0-1.6 kg). Surgical preparation consisted of a tracheotomy, femoral arterial and venous cannulation, and a midline laparotomy through which a 13-cm loop of ileum was exteriorized and superfused with physiological salt solution. Mesenteric vein diameter and intravenous pressure (using a servo-null measurement system) were measured in 500- to 1,000-micron mesenteric veins during 40-s periods of 15%, 20%, and 25% CO2 inhalation. Measurements were then repeated following bilateral ablation of the carotid chemoreceptors. Before denervation, mesenteric vein diameter constricted 6.5 +/- 1.1%, 11.9 +/- 1.1%, and 17.9 +/- 2.2% during the 15%, 20%, and 25% CO2 inhalation, respectively. After denervation, these values were reduced to 5.0 +/- 0.9%, 6.9 +/- 1.2%, and 8.4 +/- 1.3%, respectively. We conclude that activation of the carotid chemoreceptors by hypercapnia induces active mesenteric venoconstriction. After denervation of the carotid baroreceptors and chemoreceptors, there was also a small decrease in venule diameter proportional to the level of inspired CO2. We further conclude that noncarotid body chemoreceptor activation contributes to mesenteric venular constriction.

The novel hypothalamic peptides orexin-A and orexin-B are known to induce feeding behavior when administered intracerebroventricularly, but little is known about other physiological functions. The renal sympathetic nerves play important roles in the homeostasis of body fluids and the circulatory system. We examined the effects of intracerebroventricularly administered orexins on mean arterial pressure (MAP), heart rate (HR), renal sympathetic nerve activity (RSNA), and plasma catecholamine in conscious rats. Orexin-A (0.3, 3. 0 nmol) provoked an increase in MAP (94.3 +/- 0.7 to 101.9 +/- 0.7 mmHg and 93.1 +/- 1.1 to 108.3 +/- 0.8 mmHg, respectively) and RSNA (28.0 +/- 7.0 and 57.9 +/- 12.3%, respectively). Similarly, orexin-B (0.3, 3.0 nmol) increased MAP (93.9 +/- 0.9 to 97.9 +/- 0.9 mmHg and 94.5 +/- 1.1 to 105.3 +/- 1.7 mmHg, respectively). Orexin-A and -B at 3.0 nmol also increased HR. In other conscious rats, a high dose of orexin-A and -B increased plasma norepinephrine. Plasma epinephrine only increased with a high dose of orexin-A. These results indicate that central orexins regulate sympathetic nerve activity and affect cardiovascular functions.

The present study was performed to determine whether renal efferent sympathetic neurons could be identified using a retrograde neuronal tracer without compromising renal function and whether the labeling and identification procedure alters Ca(2+) currents and neuromodulation of those neurons. Renal sympathetic and superior cervical ganglion (SCG) neurons were labeled with the fluorescent retrograde tracer fast blue. Renal function studies made 1 wk after labeling revealed that renal hemodynamics and fluid and electrolyte excretion were similar between the dye-injected (left) kidney and the control (right) kidney under control conditions and after hemorrhage. After volume expansion, urine flow in the dye-injected kidney was slightly, but significantly, less than that of the control kidney, whereas urinary sodium excretion increased by approximately ninefold in both kidneys. Patch-clamp studies of SCG neurons in 10 mM external Ca(2+) revealed that peak currents were not affected by the presence of the dye or a 1-min exposure to ultraviolet (UV) light. Neither maximal norepinephrine-induced Ca(2+) current inhibition nor the sensitivity to norepinephrine was affected by the dye or 1-min UV exposure. Facilitation protocols revealed that G protein modulation of Ca(2+) currents remained intact in dye-labeled UV-exposed neurons. This study demonstrates that a retrograde fluorescent dye technique to identify renal sympathetic neurons does not compromise renal function and the presence of the dye label or UV exposure has no effect on Ca(2+) currents and neuromodulation in these neurons. Isolation of single identified renal sympathetic neurons coupled with patch-clamp techniques represents a tool to investigate the role of individual current systems in the modulation of excitability in these neurons, which play an important role in the control of renal hemodynamics and excretory function and in the pathogenesis of hypertension.

This study was designed to test the hypothesis that the medullary lateral tegmental field (LTF) is an important synaptic relay in the baroreceptor reflex pathway controlling sympathetic nerve discharge (SND) of urethan-anesthetized cats. We determined the effects of blockade of excitatory amino acid-mediated neurotransmission in the LTF on three indexes of baroreceptor reflex function: cardiac-related power in SND, strength of linear correlation (coherence value) of SND to the arterial pulse (AP), and inhibition of SND during increased arterial pressure produced by abrupt obstruction of the abdominal aorta. Bilateral microinjection of D-(-)-2-amino-5-phosphonopentanoic acid, an N-methyl-D-aspartate (NMDA) receptor antagonist, abolished cardiac-related power and coherence of SND to the AP, and it prevented inhibition of SND during aortic obstruction. These data support the view that NMDA receptor-mediated neurotransmission in the LTF is critical for baroreceptor reflex control of SND. Bilateral microinjection of 1,2, 3,4-tetrahydro-6-nitro-2,3-dioxobenzo-[f]-quinoxaline-7-sulfonamid e, a non-NMDA receptor antagonist, decreased cardiac-related power and total power in the 0- to 6-Hz band of SND; however, the AP-SND coherence value remained high, and inhibition of SND during aortic obstruction was preserved. These data imply that non-NMDA receptor-mediated neurotransmission in the LTF is involved in setting the level of excitatory drive to sympathetic nerves.

Previous work in our laboratory has demonstrated impairment of cardiopulmonary reflex control of renal sympathetic nerve activity (RSNA) during the newborn period. The present study was designed to test the hypothesis that this delayed maturation is secondary to incomplete central integration of vagal afferent input. Term fetal (135-140 days; n = 6), newborn (3-7 days of age; n = 8), and young adult (6-8 wk old; n = 8) sheep anesthetized with alpha-chloralose underwent vagal afferent nerve stimulation. All animals had undergone prior sinoaortic denervation to eliminate influences from the arterial baroreceptors. After determination of optimal stimulation parameters, RSNA responses to gradual increases in stimulation frequency (1.0-16 Hz) were recorded and compared by one-way ANOVA. RSNA decreased progressively with increased frequency of stimulation in all three groups of animals. When comparing the three groups at any given frequency of stimulation, reflex withdrawal of RSNA tended to be more pronounced in newborn lambs (P < 0.05 for 1 and 4 Hz). Heart rate (HR) was also noted to decrease significantly with vagal afferent stimulation in each of the groups, but no significant differences in the reflex decreases in HR were noted among the three groups of animals. These results demonstrate that central integration of vagal afferent input is intact in fetal and newborn sheep. These results suggest that the delayed maturation of cardiopulmonary reflex-mediated changes in RSNA seen early in development appears to depend on intrinsic alterations in baroreceptor function rather than incomplete central integration.

To further investigate neural effects on leptin and uncoupling proteins (UCPs), we studied in vivo perturbations intended to block adrenergic input to peripheral tissues. We examined plasma leptin, leptin mRNA, and adipose and muscle UCP subtype mRNA in rats treated with alpha-methyl-p-tyrosine methyl ester (AMPT-ME), which inhibits catecholamine synthesis and 6-hydroxydopamine (6HDA), which is toxic to catecholinergic nerve terminals but, unlike AMPT-ME, does not enter the central nervous system. Intraperitoneal AMPT-ME, 250 mg/kg, was administered at 1800 and 0700 the following day, and rats were killed at 1200-1400. All rats were fasted with free access to water during this time. Intraperitoneal AMPT-ME increased plasma leptin by 15-fold, increased interscapular brown adipose tissue (IBAT) and epididymal fat leptin mRNA by 2- to 2.5-fold, and also increased plasma insulin and glucose concentrations. Intraperitoneal AMPT-ME decreased IBAT UCP-3 mRNA to 40% of control, while it increased epididymal adipose UCP-3 mRNA approximately twofold. Intravenous AMPT-ME, 250 mg/kg, administered to conscious rats for 5 h decreased lumbar sympathetic nerve activity, increased plasma leptin (5.89 +/- 1.43 compared with 2.75 +/- 0.31 ng/ml in vehicle-treated rats, n = 7, P < 0.05), and decreased cardiac rate with no sustained change in blood pressure. Intraperitoneal 6HDA, 100 mg/kg, as a single dose at 1800, increased plasma leptin approximately twofold after 18-20 h, increased IBAT (but not epididymal fat) leptin mRNA by two- to threefold, and decreased IBAT UCP-3 mRNA to 30-40% of control. Neither AMPT-ME nor 6HDA significantly altered mRNA encoding gastrocnemius muscle UCP-3, IBAT UCP-1, or IBAT and epididymal UCP-2. In summary, AMPT-ME and 6HDA increased plasma leptin and upregulated leptin mRNA expression. AMPT-ME also resulted in complex tissue and subtype-specific modulation of adipose UCP mRNA. These data are consistent with interaction between leptin and sympathetic nerve activity (SNA) in regulation of fat cell energy utilization. However, the in vivo modulation of leptin and UCPs appears complex and, beyond a causal effect of SNA per se, may depend on concurrent changes in plasma insulin, glucose, and circulatory hemodynamics.

The present study investigated the role of the renal nerves in mediating the cardiovascular and renal responses produced by the central administration of the opioid-like peptide orphanin FQ/nociceptin (OFQ/N) in conscious Sprague-Dawley rats. In conscious rats, OFQ/N (10 microgram icv) produced a transient bradycardia and hypotension (nadir 20 min). Although renal sympathetic nerve activity (RSNA) initially remained unchanged, a delayed renal sympathoinhibitory response occurred after recovery (30 min) of blood pressure. By 30 and 70 min postinjection, RSNA decreased to 75 and 66% of control, respectively. Coinciding with the decrease in RSNA, central OFQ/N elicited a diuresis and antinatriuresis that occurred independent of changes in renal hemodynamics. In other studies, intracerebroventricular OFQ/N produced similar cardiovascular and renal excretory responses in bilaterally renal-denervated rats. Finally, in conscious sinoaortic deafferentiated rats, intracerebroventricular OFQ/N produced a rapid decrease in RSNA (55% of control, 10 min; 38% of control, 20 min) that paralleled the onset of the hypotension and bradycardia. These studies demonstrate that in conscious rats, intracerebroventricular OFQ/N produces a centrally mediated inhibition of RSNA which, due to activation of baroreflex mechanisms, is temporally dissociated from the hypotensive and bradycardia responses. As revealed in renal-denervated rats, the cardiovascular and renal excretory responses produced by central OFQ/N occur by a pathway that is independent of intact renal nerves or changes in renal hemodynamics.

We examined whether the altered orthostatic tolerance following 14 days of head-down tilt bed rest (HDBR) was related to inadequate sympathetic outflow or to excessive reductions in cardiac output during a 10- to 15-min head-up tilt (HUT) test. Heart rate, blood pressure (BP, Finapres), muscle sympathetic nerve activity (MSNA, microneurography), and stroke volume blood velocity (SVV, Doppler ultrasound) were assessed during supine 30 degrees (5 min) and 60 degrees (5-10 min) HUT positions in 15 individuals who successfully completed the pre-HDBR test without evidence of orthostatic intolerance. Subjects were classified as being orthostatically tolerant (OT, n = 9) or intolerant (OI, n = 6) following the post-HDBR test. MSNA, BP, and SVV during supine and HUT postures were not altered in the OT group. Hypotension during 60 degrees HUT in the post-bed rest test for the OI group (P < 0.05) was associated with a blunted increase in MSNA (P < 0.05). SVV was reduced following HDBR in the OI group (main effect of HDBR, P < 0.02). The data support the hypothesis that bed rest-induced orthostatic intolerance is related to an inadequate increase in sympathetic discharge that cannot compensate for a greater postural reduction in stroke volume.

Nociceptin, an endogenous agonist of the opioid receptor-like(1) receptor, is expressed in the hypothalamus, where it is implicated in autonomic nervous system control. However, the central actions of nociceptin on sympathetic nerve activity have not been studied. We investigated the effect of intracerebroventricularly administered nociceptin (2-10 nmol) on blood pressure, heart rate (HR), and renal sympathetic nerve activity (RSNA) in conscious rats and sinoaortic-denervated (SAD) rats. Intracerebroventricularly administered nociceptin resulted in a dose-dependent decrease in mean arterial pressure (MAP) and HR in intact rats. RSNA decreased 31.5 +/- 2.1 and 19.9 +/- 5.0% at a dose of 2 and 5 nmol, respectively. In SAD rats, MAP, HR, and RSNA decreased in a dose-dependent manner, and the maximum responses were larger than those in intact rats. The decrease in HR induced by nociceptin was blocked by propranolol but not by atropine, which indicates that nociceptin is acting by inhibiting cardiac sympathetic outflow. These nociceptin-induced depressor and bradycardic responses were not antagonized by pretreatment with naloxone and nocistatin. These findings suggest that central nociceptin may have a functional role in regulating cardiovascular and sympathetic nervous systems.

The developmental increase in L-type Ca current (I(Ca,L)) density in the rat ventricle is reproduced in vitro by culturing neonatal myocytes with sympathetic neurons. We tested whether this effect of sympathetic innervation results from a chronic or sustained action of neurally released neuropeptide Y (NPY). Ventricular myocytes from newborn rats were cultured in serum-free medium with or without sympathetic neurons, NPY, or NPY analogs. Ca currents were measured in single myocytes at room temperature using the perforated patch clamp. In all cell groups (control, innervated, or NPY treated), the current-voltage relation for I(Ca,L) was represented by a bell-shaped curve with maximal value near 0 mV. The current density at 0 mV normalized to that of corresponding mean control values was 1.63 +/- 0.12 and 1.52 +/- 0.16 for innervated and NPY-treated myocytes, respectively. Both groups differed significantly from control (P < 0.05). NPY analogs exhibited the following rank order of effectiveness: NPY >/= NPY-(13-36) >/= PYY >> [Leu31Pro34]NPY, suggesting that the NPY effect occurs via a Y2-receptor subtype. In confirmation, chronic treatment of innervated cultures with a Y2-selective NPY antagonist prevented the innervation-dependent increase in I(Ca,L). These results indicate that sympathetic innervation contributes to the developmental increase in I(Ca,L) via neurally released NPY acting at Y2 receptors on the ventricular myocytes.

An intravenous injection of 2 microg of [Asp1,Val5]-ANG II attenuated fluid secretion by the nasal salt glands of Pekin ducks. Ganglionic blockade with mecamylamine stopped salt gland secretion. Flow was reestablished by intravenous methacholine bromide during ganglionic blockade. A second injection of 2 microg of [Asp1, Val5]-ANG II failed to attenuate secretion during ganglionic blockade, showing that the peptide acts via the central nervous system and postganglionic parasympathetic nerves that supply the salt glands. Sympathetic nerves are located in the walls of blood vessels within the salt glands, and adrenergic fibers with "varicosities" supply extensively the secretory tubules. [Asp1, Val5]-ANG II decreased salt gland secretion both before and after alpha1-adrenergic blockade with prazosin, showing that the lowered activity was not caused by the release of norepinephrine from nerve endings and/or duck adrenal chromaffin cells. beta-Adrenergic blockade with propranolol also failed to prevent the attenuation of secretion in response to an intravenous injection of 2 microg of [Asp1,Val5]-ANG II, which showed that epinephrine did not mediate the response to the peptide.

The object of this study is to quantify the very low frequency (i.e., <0.1 Hz) interactions between renal sympathetic nerve activity (SNA) and arterial blood pressure (ABP). Six rats were instrumented for chronic recordings of SNA and ABP. Data were collected 24 h after surgery at 10 kHz for 2-5 h and subsequently compressed to a 1-kHz signal. The power spectra and ordinary coherence were calculated from data epochs up to 1 h in length. The very low frequency spectra for both variables were fitted to a constant times f (-beta). The peak magnitude squared of the coherence near 0.4 Hz was 0.82 +/- 0.08, but the apparent linear coherence fell off quickly at lower frequencies so that it was close to zero for frequencies <0.1 Hz. Moreover, at these low frequencies beta, as computed by a coarse grain spectral analysis, was significantly (P < 0.01) different for SNA (0.66 +/- 0.12) and ABP (1.12 +/- 0.14). Assuming that SNA and ABP are stationary time series, the results of our classical spectral analysis would indicate that SNA and ABP are not linearly correlated at frequencies with a period more than approximately 10 s. Accordingly, we tested for stationarity by computing the spectral coherence and found that SNA and ABP are not stationary "1/f noise" within the frequency range from 0.02 to 2.0 Hz. Rather the SNA exerts control over the cardiovascular system through intermittent bursts of activity. Such intermittent behavior can be modeled by nonlinear dynamics.

To evaluate whether sympathetic activity induces nitric oxide (NO) production, we perfused the rat arterial mesenteric bed and measured luminally accessible norepinephrine (NE), NO, and cGMP before, during, and after stimulation of perivascular nerves. Electrical stimulation (1 min, 30 Hz) raised perfusion pressure by 97 +/- 7 mmHg, accompanied by peaks of 23 +/- 3 pmol NE, 445 +/- 48 pmol NO, and 1 pmol cGMP. Likewise, perfusion with 10 microM NE induced vasoconstriction coupled to increased NO and cGMP release. Electrically elicited NO release depended on stimulus frequency and duration. Endothelium denudation with saponin abolished the NO peak without changing NE release. Inhibition of NO synthase with 100 microM N(omega)-nitro-L-arginine reduced basal NO and cGMP release and blocked the electrically stimulated and exogenous NE-stimulated NO peak while enhancing vasoconstriction. Blocking either sympathetic exocytosis with 1 microM guanethidine or alpha1-adrenoceptors with 30 nM prazosin abolished the electrically evoked vasoconstriction and NO release. alpha2-Adrenoceptor blockade with 1 microM yohimbine reduced both vasoconstriction and NO peak while increasing NE release. In summary, sympathetically released NE induces vasoconstriction, which triggers a secondary release of endothelial NO coupled to cGMP production.

In a previous study, we reported that vestibular nerve stimulation in the cat elicits a specific pattern of sympathetic nerve activation, such that responses are particularly large in the renal nerve. This patterning of vestibulosympathetic reflexes was the same in anesthetized and decerebrate preparations. In the present study, we report that inputs from skin and muscle also elicit a specific patterning of sympathetic outflow, which is distinct from that produced by vestibular stimulation. Renal, superior mesenteric, and lumbar colonic nerves respond most strongly to forelimb and hindlimb nerve stimulation (approximately 60% of maximal nerve activation), whereas external carotid and hypogastric nerves were least sensitive to these inputs (approximately 20% of maximal nerve activation). In contrast to vestibulosympathetic reflexes, the expression of responses to skin and muscle afferent activation differs in decerebrate and anesthetized animals. In baroreceptor-intact animals, somatosympathetic responses were strongly attenuated (to <20% of control in every nerve) by increasing blood pressure levels to >150 mmHg. These findings demonstrate that different types of somatic inputs elicit specific patterns of sympathetic nerve activation, presumably generated through distinct neural circuits.