Biomedical subjects

Carolyn J Barrett

Publications and source records attributed to Carolyn J Barrett.

18 recordsLinked to original sources

PubMed2007

Role of renal sympathetic nerve activity in hypertension induced by chronic nitric oxide inhibition.

Nitric oxide levels are diminished in hypertensive patients, suggesting nitric oxide might have an important role to play in the development of hypertension. Chronic blockade of nitric oxide leads to hypertension that is sustained throughout the period of the blockade in baroreceptor-intact animals. It has been suggested that the sympathetic nervous system is involved in the chronic increase in blood pressure; however, the evidence is inconclusive. We measured renal sympathetic nerve activity and blood pressure via telemetry in rabbits over 7 days of nitric oxide blockade. Nitric oxide blockade via N(omega)-nitro-L-arginine methyl ester (L-NAME) in the drinking water (50 mg x kg(-1) x day(-1)) for 7 days caused a significant increase in arterial pressure (7 +/- 1 mmHg above control levels; P < 0.05). While the increase in blood pressure was associated with a decrease in heart rate (from 233 +/- 6 beats/min before the L-NAME to 202 +/- 6 beats/min on day 7), there was no change in renal sympathetic nerve activity (94 +/- 4 %baseline levels on day 2 and 96 +/- 5 %baseline levels on day 7 of L-NAME; baseline nerve activity levels were normalized to the maximum 2 s of nerve activity evoked by nasopharyngeal stimulation). The lack of change in renal sympathetic nerve activity during the L-NAME-induced hypertension indicates that the renal nerves do not mediate the increase in blood pressure in conscious rabbits.

Animals↗

PubMed2007

Novel technology for the provision of power to implantable physiological devices.

We report the development of a novel technology that enables the wireless transmission of sufficient amounts of power to implantable physiological devices. The system involves a primary unit generating the magnetic field and a secondary pickup unit deriving power from the magnetic field and a power conditioner. The inductively coupled system was able to supply a minimum of 20 mW at all locations and pickup orientations across a rat cage, although much higher power of up to 10 W could be achieved. We hypothesized that it would be possible to use this technology to record a high-fidelity ECG signal in a conscious rat. A device was constructed in which power was utilized to recharge a battery contained within a telemetry device recording ECG signal sampled at 2,000 Hz in conscious rats (200-350 g) living in their home cage. Attributes of the ECG signal (QT, QRS, and PR interval) could be obtained with a high degree of accuracy (<1 ms). ECG and heart rate changes in response to treatment with the beta blocker propranolol and the proarrhythmic alkaloid aconitine were measured. Transmitters were implanted for up to 4 mo, and the characteristic circadian variation in heart rate was recorded. Such technology allows potentially lifetime monitoring without the need for implant refurbishment. The ability to provide suitable power levels to implanted devices without concern to the orientation of the device and without causing heating provides the basis for the development of new devices to record or influence physiological signals in animals or humans over significantly longer time periods than can currently be accommodated.

Animals↗

PubMed2006

The influence of heart rate on baroreceptor fibre activity in the carotid sinus and aortic depressor nerves of the rabbit.

The arterial baroreceptors and their afferent fibres provide the sensory arm of the reflex that regulates systemic arterial pressure. We have examined whether the relationship between mean baroreceptor discharge and mean arterial pressure is altered when heart rate changes. Experiments were performed on pentobarbitone-anaesthetized rabbits. We recorded the activity of single and multifibre preparations of the carotid sinus (CSN) and aortic depressor nerves (ADN). Data were collected under control conditions and while heart rate was increased by approximately 30-35% by right atrial pacing. Baroreceptor regions were exposed to ramps of pressure (from approximately 25 to 140 mmHg, at approximately 0.5-1 mmHg s(-1)), generated by inflation and deflation of cuffs placed around the inferior vena cava and descending thoracic aorta. Response curves relating baroreceptor discharge to mean pressure were constructed and fitted with third-order polynomial expressions. To provide a measure of an effect of an increase in heart rate on the response curve in the region of the normal operating pressure, we calculated the position of the test response curve relative to the position of the control curve at 90 mmHg (deltaBP(90)). For the ADN, the activity of single fibres (presumptive myelinated fibres) was unaffected by increasing heart rate (deltaBP(90) = +0.1 +/- 1.0 mmHg), while single fibres in the CSN showed a small increase in activity (deltaBP(90) = -1.5 +/- 0.3 mmHg). In multifibre preparations there was a small increase in activity that may be attributable to additional activity in unmyelinated fibres (ADN, deltaBP(90) = -3.4 +/- 1.2 mmHg; CSN, deltaBP(90) = -5.2 +/- 0.9 mmHg). We conclude that the mean discharge of arterial baroreceptors remains a reliable index of mean arterial pressure in the presence of substantial changes in heart rate.

Animals↗

PubMed2006

Baroreflex mechanisms regulating mean level of SNA differ from those regulating the timing and entrainment of the sympathetic discharges in rabbits.

The arterial baroreflex pathway provides the fundamental basis for the short-term control of blood pressure via the rapid regulation of the mean level of sympathetic nerve activity (SNA) in response to changes in blood pressure. A central tenet in the generation and regulation of bursts of SNA is that input from the arterial baroreceptors also regulates the timing of the bursts of sympathetic activity. With the use of an implantable telemetry-based amplifier, renal SNA was recorded in intact and arterial baroreceptor-denervated (SAD) conscious rabbits. Data were collected continuously while animals were in their home cage. Mean levels of SNA were not different between SAD and baroreceptor-intact animals. Whereas SNA was unresponsive to changes in blood pressure in SAD rabbits, the timing of the bursts of SNA relative to the arterial pulse wave was maintained (time between the diastolic pressure and the next maximum SNA voltage averaged 107+/-12 ms SAD vs. 105+/-7 ms intact). Transfer function analysis between blood pressure and SNA indicates the average gain at the heart rate frequency was not altered by SAD, indicating strong coupling between the cardiac cycle and SNA bursts in SAD animals. Further experiments in anesthetized rabbits showed that this entrainment is lost immediately after performing baroreceptor denervation surgery and remained absent while the animal was under anesthesia but returned within 20 min of turning off the anesthesia. We propose that this finding indicates the regulation of the mean level of SNA requires the majority of input from baroreceptors to be functional; however, the regulation of the timing of the bursts in the conscious animal requires only minimal input, such as a sensitive trigger mechanism. This observation has important implications for understanding the origin and regulation of SNA.

Animals↗

PubMed2006

Renal sympathetic nerve activity in the development of hypertension.

With increasing evidence that the sympathetic nervous system plays a critical role in the development of hypertension, focus is turning to how these signals translate to a chronic increase in arterial pressure. The kidney's role in the control of salt and water homeostasis makes it an obvious target for such investigations. However, to date many studies have been restricted to experiments that last only a few hours, or at most, a few days, whereas others may use indirect methods of assessing sympathetic activity rather than direct recordings. We review current approaches used to determine the effects of renal sympathetic nerve activity (SNA) on arterial pressure and suggest possible avenues of future investigation. We propose that although afferent inputs, such those as from chemoreceptors and baroreceptors, are important for the short-term control of blood pressure via regulation of SNA to multiple organs, it is highly likely that alternative signals are important for setting the long-term level of renal SNA. Emerging evidence indicates that circulating angiotensin II is a hormone that may act on the central nervous system to regulate renal SNA, renal function, and, therefore, blood pressure. Future studies on the genesis of hypertension should focus more on determining the mediators of long-term levels of renal SNA.

Angiotensin II↗

PubMed2005

Evidence of differential control of renal and lumbar sympathetic nerve activity in conscious rabbits.

We have explored the possibility that renal sympathetic nerve activity (RSNA) and vasomotor sympathetic nerve activity are differentially regulated. We measured sympathetic nerve activity (SNA) to the kidney and the hind limb vasculature in seven conscious rabbits 6-8 days after the implantation of recording electrodes. Acute infusion of N(G)-nitro-L-arginine methyl ester (L-NAME) (6 mg.kg(-1).min(-1) for 5 min) led to an increase in blood pressure (from 66 +/- 1 to 82 +/- 3 mmHg) and a decrease in heart rate (from 214 +/- 15 to 160 +/- 13 bpm). L-NAME administration caused a significantly greater decrease in RSNA than lumbar sympathetic nerve activity (LSNA) (to 68 +/- 14% vs. 84 +/- 4% of control values, respectively). Volume expansion (1.5 ml.kg(-1).min(-1)) resulted in a significant decrease in RSNA to 66 +/- 7% of control levels but no change in LSNA (127 +/- 20%). There was no difference in the gain of the baroreflex curves between the LSNA and RSNA [maximum gain of -7.6 +/- 0.4 normalized units (nu)/mmHg for LSNA vs. -7.9 +/- 0.75 nu/mmHg for RSNA]. A hypoxic stimulus (10% O2 and 3% CO2) led to identical increases in both RSNA and LSNA (195 +/- 40% and 158 +/- 21% of control values, respectively). Our results indicate tailored differential control of RSNA and LSNA in response to acute stimuli.

Animals↗

PubMed2005

Baroreceptor denervation prevents sympathoinhibition during angiotensin II-induced hypertension.

Arterial baroreflexes are well established to provide the basis for short-term control of arterial pressure; however, their role in long-term pressure control is more controversial. We proposed that if the sustained decrease in renal sympathetic nerve activity (RSNA) we observed previously in response to angiotensin II-induced hypertension is baroreflex mediated, then the decrease in RSNA in response to angiotensin II would not occur in sinoaortic-denervated (SAD) animals. Arterial pressure and RSNA were recorded continuously via telemetry in sham and SAD rabbits living in their home cages before, during, and after a 7-day infusion of angiotensin II (50 ng . kg(-1) . min(-1)). The arterial pressure responses in the 2 groups of rabbits were not significantly different (82+/-3 mm Hg sham versus 83+/-3 mm Hg SAD before angiotensin II infusion, and 101+/-6 mm Hg sham versus 100+/-4 mm Hg SAD day 6 of angiotensin II). In sham rabbits, there was a significant sustained decrease in RSNA (53+/-7% of baseline on day 2 and 65+/-7% on day 6 of the angiotensin II). On ceasing the angiotensin II, all variables recovered to baseline. In contrast, RSNA did not change in SAD rabbits with the angiotensin II infusion (RSNA was 98+/-8% of baseline on day 2 and 98+/-8% on day 6 of the angiotensin II infusion). These results support our hypothesis that the reduction in RSNA in response to a pressor dose of angiotensin II is dependent on an intact arterial baroreflex pathway.

Angiotensin II↗

PubMed2005

Problems, possibilities, and pitfalls in studying the arterial baroreflexes' influence over long-term control of blood pressure.

While there is no disputing the critical role of baroreflexes in buffering rapid changes in arterial pressure, their role in long-term pressure control has become an area of controversy. Recent experiments using novel techniques have challenged the traditional view that arterial baroreflexes are not involved in setting chronic arterial pressure levels. Resetting of the arterial baroreflex, often used as an argument against the arterial baroreflex playing a role in long-term pressure control is rarely complete. The arterial baroreflex is just one of the many neural, hormonal, and intrinsic mechanisms involved in arterial pressure control and while the removal of the arterial baroreflex alone has little effect on mean arterial pressure it is too simplistic to suggest that the baroreflex has no role in long-term pressure control. Renal sympathetic nerve activity appears to be particularly resistant to resetting in response to ANG II-induced hypertension. Given the important role of the kidneys in long-term pressure control, we suggest there is a clear need to develop experimental techniques whereby sympathetic nerve activity to the kidneys and other organs can be monitored over periods of weeks to months.

Angiotensin II↗

PubMed2003

Chronic blockade of nitric oxide does not produce hypertension in baroreceptor denervated rabbits.

Although the vascular action of endothelium-derived nitric oxide in modulating arterial pressure is well established, nitric oxide can also act as a neurotransmitter in the central nervous system. In addition, there is evidence for an interaction between nitric oxide and baroreceptor afferent processing; thus, nitric oxide may regulate blood pressure through central modulation of arterial baroreflexes. To test this possible interaction of nitric oxide and baroreflexes in the long-term regulation of blood pressure, we measured arterial pressure and heart rate responses to nitric oxide blockade by using L-NAME (50 mg/kg per day in drinking water) over 7 days in baroreceptor intact and sinoaortic denervated conscious rabbits. In the baroreceptor intact animals, blockade of nitric oxide leads to a significant increase in mean arterial pressure (from 75+/-2 to 84+/-3 mm Hg) and decrease in heart rate (from 233+/-8 to 195+/-8 bpm) that was sustained over the 7 days of nitric oxide blockade. In the sinoaortic denervated animals, blockade of nitric oxide initially led to a similar increase in arterial pressure (82+/-3 mm Hg on the second day), but in all sinoaortic denervated animals this increase was not sustained and recovered back to pre-L-NAME levels. This finding indicates that baroreflexes play an important role in the long-term control of blood pressure, and, second, that one mediator of this control is nitric oxide.

Animals↗

PubMed2003

What sets the long-term level of renal sympathetic nerve activity: a role for angiotensin II and baroreflexes?

Increasing evidence suggests elevated sympathetic outflow may be important in the genesis of hypertension. It is thought that peripheral angiotensin II, in addition to its pressor actions, may act centrally to increase sympathetic nerve activity (SNA). Without direct long-term recordings of SNA, testing the involvement of neural mechanisms in angiotensin II-induced increases in arterial pressure is difficult. Using a novel telemetry-based implantable amplifier, we made continuous recordings of renal SNA (RSNA) before, during, and after 1 week of angiotensin II-based hypertension in rabbits living in their home cages. Angiotensin II infusion (50 ng x kg(-1) x min(-1)) caused a sustained increase in arterial pressure (18+/-3 mm Hg). There was a sustained decrease in RSNA from 18+/-2 normalized units (n.u.) before angiotensin II to 8+/-2 n.u. on day 2 and 9+/-2 n.u. on day 7 of the angiotensin II infusion (P<0.01) before recovering to 17+/-2 n.u. after ceasing angiotensin II. Analysis of the baroreflex response showed that although angiotensin II-induced hypertension led to resetting of the relationship between mean arterial pressure (MAP) and heart rate, there was no evidence of resetting of the MAP-RSNA relationship. We propose that the lack of resetting of the MAP-RSNA curve, with the resting point lying near the lower plateau, suggests the sustained decrease in RSNA during angiotensin II is baroreflex mediated. These results suggest that baroreflex control of RSNA and thus renal function is likely to play a significant role in the control of arterial pressure not only in the short term but also in the long term.

Angiotensin II↗

PubMed2003

Role of angiotensin II in the neural control of renal function.

The aim of the present study was to distinguish between the direct effects of the renal nerves on renal function and indirect effects via neurally mediated increased systemic angiotensin II. We applied low-level electrical stimulation (1 Hz) to the left renal nerves in pentobarbitone-anesthetized rabbits for 180 minutes and measured renal blood flow, sodium excretion, and urine flow rate from both the stimulated and the nonstimulated contralateral kidney in the presence and the absence of ACE inhibition (enalaprilat). Stimulation resulted in an angiotensin II-mediated rise in arterial pressure and decreases in renal blood flow, urine flow rate, and sodium excretion on the stimulated side. On the nonstimulated denervated side, we found no change in renal blood flow, but found a decrease in urine flow rate. With ACE inhibition, renal stimulation no longer caused an increase in arterial pressure, the antidiuretic responses of the stimulated kidney were attenuated, and, importantly, the decrease in urine flow rate on the nonstimulated kidney was completely abolished. We therefore propose that although a direct effect of the renal nerves on sodium excretion is clearly present, the antidiuresis and antinatriuresis observed during renal activation is further supported by a neurally mediated increase in systemic angiotensin II.

Angiotensin II↗

PubMed2003

Interactions between neural and hormonal mediators of renal vascular tone in anaesthetized rabbits.

We investigated how sympathetic nerve activity and vasoactive hormones interact in controlling renal haemodynamics in pentobarbitone-anaesthetized rabbits. Renal blood flow was progressively reduced by electrical stimulation (0.5-3 Hz) of the renal nerves, during renal arterial infusion of saline, vasoconstrictors (angiotensin II and [Phe2,Ile3,Orn8]-vasopressin), or vasodilators (acetylcholine, adrenomedullin and the nitric oxide donor methylamine hexamethylene NONOate (MAHMA NONOate). A frequency-rich stimulus was also applied to test whether the vasoactive agents affect the dynamic control of renal blood flow by sympathetic nerve activity. The vasodilators tended to increase renal blood flow, but only the effect of MAHMA NONOate was statistically significant. [Phe2,Ile3,Orn8]-vasopressin reduced medullary perfusion (by 61 +/- 12 %) but not renal blood flow or cortical perfusion. Angiotensin II reduced renal blood flow (33 +/- 3 %) and cortical perfusion (14 +/- 5 %) but not medullary perfusion. Steady-state responses of renal blood flow and cortical perfusion during renal nerve stimulation were attenuated during infusion of acetylcholine and [Phe2,Ile3,Orn8]-vasopressin, while angiotensin II attenuated responses of medullary perfusion, and MAHMA NONOate and adrenomedullin had no significant effects. The dynamic response to sympathetic nerve activity (renal blood flow responded as a low pass filter with a pure time delay of ~664 ms) was not altered by the vasoactive agents. We conclude that some vasoactive agents can modulate steady-state renal haemodynamic responses to sympathetic nerve activity in a regionally specific manner, independent of their effects on baseline renovascular tone. However, they have little impact on the dynamic response of renal blood flow to sympathetic nerve activity.

Acetylcholine↗

PubMed2002

Neural control of the renal vasculature in angiotensin II-induced hypertension.

1. Chronic administration of angiotensin (Ang) II causes an increase in blood pressure via a multitude of actions, including direct vasoconstriction, hypertrophy and increased sympathetic nerve activity. In the present study, we assessed whether the hypertension resulting from chronic Ang II alters the ability of the renal vasculature to respond to sympathetic activity. 2. Angiotensin II was administered for 7 weeks via an osmotic minipump at a dose of 50 ng/kg per min, i.v., to a group of six rabbits. Blood pressure, measured at 0, 1, 2 and 6 weeks after insertion of the pump, increased from 76 +/- 2 to 104 +/- 6 mmHg at the end of 6 weeks, without any significant change in heart rate. The blood pressure in the control group remained constant at 76 +/- 2 mmHg. 3. After 7 weeks, rabbits were anaesthetized and the renal nerves were stimulated at 0.5, 1, 1.5, 2, 3, 5 or 8 Hz for 3 min at their supramaximal voltage (5.5 +/- 1.0 V in the normotensive group and 6.5 +/- 1.5 V in the hypertensive group) while the renal blood flow (RBF) response was recorded. Under anaesthesia, there was no difference in mean arterial pressure between the normotensive and hypertensive animals (77 +/- 2 and 80 +/- 7 mmHg, respectively). The resting RBF under these conditions was not significantly different in the hypertensive group (30 +/- 4 vs 26 +/- 5 mL/min in the normotensive vs hypertensive group, respectively). 4. Stimulation at increasing frequencies was associated with increasing reductions in RBF (e.g. 36 +/- 8% at 2 Hz in normotensive rabbits and 48 +/- 7% at 2 Hz in hypertensive rabbits). However, there were no significant differences between RBF responses in normotensive and hypertensive rabbits. 5. We conclude that hypertension associated with chronic Ang II administration does not alter the response in RBF to electrical stimulation of the nerves.

Angiotensin II↗

PubMed2002

A real-time algorithm for the quantification of blood pressure waveforms.

A real-time algorithm for quantification of biological oscillatory signals, such as arterial blood pressure (BP) is proposed which does not require user intervention and works on waveforms complicated by rapid changes in the mean level, frequency, or by the presence of arrhythmia. The algorithm is based on the continous independent assessment of the refractory period (RP). In the first stage, a sample of the signal is band-pass filtered. During the next stage: 1) the local maxima in the filtered signal are identified and their pulse amplitudes (PA) measured on the side opposite to the possible notch position and 2) those maxima whose PA exceeds some threshold are selected and an array of RP values is formed as a fraction of the moving estimate of the interval between successive selected peaks. Finally, the original signal is analyzed by means of two moving averages (MAs) with short and long averaging time intervals. The true peaks are determined as the maxima between intersections of MAs if the peak-to-peak or the intersection-to-intersection intervals since the previous peak and the previous intersection exceed the RP. The algorithm proved to be superior against three commercially available heartbeat detectors yielding an error rate of 0.09%.

Algorithms↗

PubMed2002

Is the chronically denervated kidney supersensitive to catecholamines?

One method for discerning the role of the renal sympathetic nerves in the regulation of renal function has been to chronically denervate one kidney. One concern with this approach is that increased renal responsiveness to plasma levels of norepinephrine may develop over time. This may reduce the apparent magnitude of the effect of the renal nerves or indeed completely mask their effect. In the present experiment, we used the rabbit unilateral denervated kidney model to examine the acute renal blood flow responses to phenylephrine to determine if there were differences between the responses in chronically denervated kidneys compared with either intact or acutely denervated kidneys. In addition, we examined the responses in rabbits that had been made hypertensive using a continuous infusion of ANG II for 7 wk. We found that chronic denervation did not result in increased renal responsiveness to phenylephrine compared with either the intact or acutely denervated kidney, suggesting that differences in renal function between renal nerve-intact and -denervated kidneys observed in previous studies are unlikely to be confounded by supersensitivity. These results suggest that the unilateral denervated kidney model is a valid model to study the role of the renal nerves in the regulation of renal function.

Angiotensin II↗

PubMed2002

Dynamic baroreflex control of blood pressure: influence of the heart vs. peripheral resistance.

The aim in the present experiments was to assess the dynamic baroreflex control of blood pressure, to develop an accurate mathematical model that represented this relationship, and to assess the role of dynamic changes in heart rate and stroke volume in giving rise to components of this response. Patterned electrical stimulation [pseudo-random binary sequence (PRBS)] was applied to the aortic depressor nerve (ADN) to produce changes in blood pressure under open-loop conditions in anesthetized rabbits. The stimulus provided constant power over the frequency range 0-0.5 Hz and revealed that the composite systems represented by the central nervous system, sympathetic activity, and vascular resistance responded as a second-order low-pass filter (corner frequency approximately 0.047 Hz) with a time delay (1.01 s). The gain between ADN and mean arterial pressure was reasonably constant before the corner frequency and then decreased with increasing frequency of stimulus. Although the heart rate was altered in response to the PRBS stimuli, we found that removal of the heart's ability to contribute to blood pressure variability by vagotomy and beta(1)-receptor blockade did not significantly alter the frequency response. We conclude that the contribution of the heart to the dynamic regulation of blood pressure is negligible in the rabbit. The consequences of this finding are examined with respect to low-frequency oscillations in blood pressure.

Animals↗

PubMedDate not supplied

Long-term recording of sympathetic nerve activity: the new frontier in understanding the development of hypertension?

1. With increasing evidence that the sympathetic nervous system plays a critical role in the development of hypertension, focus is turning to how these signals translate to a chronic increase in arterial pressure. 2. The kidney's role in the control of salt and water homeostasis makes it an obvious target for such investigations. However, to date, many studies have been restricted to experiments lasting only a few hours or, at most, a few days, whereas others may use indirect methods of assessing sympathetic activity rather than direct recordings. 3. We review current approaches used to determine the effects of renal sympathetic nerve activity (SNA) on arterial pressure and suggest possible avenues of future investigation. We propose that although afferent inputs, such as from chemoreceptors and baroreceptors, are important for the short-term control of blood pressure via regulation of SNA to multiple organs, it is highly likely that alternative signals are important for setting the long-term level of renal SNA. 4. Emerging evidence indicates circulating angiotensin II is hormone that may act on the central nervous system to regulate renal SNA, renal function and, thus, blood pressure. 5. We propose that an integral part of future studies seeking an understanding of the genesis of hypertension should include chronic direct recordings of renal SNA.

Adrenergic Fibers↗

PubMedDate not supplied

Nitric oxide and sympathetic nerve activity in the control of blood pressure.

1. Endothelial dysfunction marked by impairment in the release of nitric oxide (NO) is seen very early in the development of hypertension and is considered important in mediating the impaired vascular tone evident in essential hypertensive patients. 2. Recently, a hypothesis has emerged that NO acting as a neurotransmitter in the brain can modulate levels of sympathetic nerve activity and thereby blood pressure. The NO inhibition model of hypertension has been used to explore the possibility that a decrease in levels of NO can cause an increase in levels of sympathetic nerve activity that can mediate the hypertension. 3. In the present review, we examine the literature regarding the role of NO in setting the mean level of sympathetic nerve activity and blood pressure. Although the acute effects of NO inhibition are well understood, the chronic interaction between the sympathetic nervous system and NO has only been investigated using indirect measures of sympathetic nerve activity, such as ganglionic blockade. This has led to inconsistent results regarding the role of NO in modulating sympathetic nerve activity chronically. 4. Some of the conflicting results may be explained by differences in the 'background' levels of angiotensin (Ang) II. Evidence suggests that NO may interact with AngII and baroreceptor afferent inputs in the central nervous system to set the mean level of sympathetic nerve activity. 5. We suggest chronic NO inhibition can increase sympathetic nerve activity if baroreceptor input is intact and AngII levels are elevated. Although studies exploring the actions of NO or AngII in isolation are useful for gathering initial information, future studies should focus on their interactions and their role in setting the long-term levels of sympathetic activity and blood pressure.

Adrenergic Fibers↗