This Article Abstract Full Text (PDF) All Versions of this Article: 46/1/168    most recent 01.HYP.0000168047.09637.d4v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Barrett, C. J. Articles by Malpas, S. C. Search for Related Content PubMed PubMed Citation Articles by Barrett, C. J. Articles by Malpas, S. C. Related Collections Hypertension - basic studies Autonomic, reflex, and neurohumoral control of circulation

(Hypertension. 2005;46:168.)
© 2005 American Heart Association, Inc.

Original Articles

Baroreceptor Denervation Prevents Sympathoinhibition During Angiotensin II–Induced Hypertension

Carolyn J. Barrett; Sarah-Jane Guild; Rohit Ramchandra; Simon C. Malpas

From the Circulatory Control Laboratory, Department of Physiology, University of Auckland, New Zealand.

Correspondence to Dr Carolyn Barrett, Department of Physiology, University of Auckland Medical School, Private Bag 92019, Auckland, New Zealand. E-mail c.barrett{at}auckland.ac.nz

	Abstract

Top Abstract Introduction Methods Results Discussion References

 
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.

Key Words: baroreceptors • denervation • rabbits • nervous system, sympathetic renal

	Introduction

Top Abstract Introduction Methods Results Discussion References

 
Arterial baroreflexes are well established to provide the basis for the short-term control of arterial pressure; however, it has generally been accepted that they do not regulate long-term pressure.¹ This concept is based on 3 main lines of evidence, the first being that arterial baroreceptors reset during sustained increases in arterial pressure.² Second, chronic sinoaortic denervation, while producing tremendous lability in arterial pressure, does not result in higher average 24-hour pressures.³ Finally, it is thought that the reflex gain of the baroreceptor control system is not sufficiently strong to explain the long-term constancy of arterial pressure.⁴ However, a number of recent experiments have renewed interest in the role of the baroreflex in long-term arterial pressure control and suggest that arterial baroreflexes may act chronically to suppress sympathetic nerve activity. Lohmeier et al⁵ studied responses to 5 days of angiotensin II infusion in dogs using a split-bladder preparation combined with denervation of 1 kidney. During angiotensin II infusion, sodium excretion from the innervated kidney significantly increased compared with the denervated kidney, indicating a decrease in renal sympathetic nerve activity (RSNA). The sustained increase in sodium excretion from the innervated kidney was proposed to be mediated by a sustained baroreflex-mediated suppression of RSNA because after cardiopulmonary and sinoaortic denervation, the sodium excretion from the innervated kidney decreased compared with the excretion from the denervated kidney during angiotensin II infusion.⁵ Thrasher⁶ developed a new surgical method to produce chronic unloading of arterial baroreceptors in dogs in which the aortic baroreceptor nerves were cut and the carotid sinus isolated from the systemic arterial pressure. Baroreceptor unloading was induced by ligation of the common carotid artery proximal to the innervated sinus. Arterial pressure was consequently increased an average of 22 mm Hg above control over 7 days, which they proposed was attributable to sustained increases in sympathetic activity. The possibility that the baroreflex may act chronically to suppress sympathetic nerve activity seems somewhat confounding given that increases in sympathetic activity have been indicated in the development of hypertension.^7,8

Recently, experiments in our own laboratory using direct recordings of RSNA indicated that RSNA was suppressed during a 7-day period of angiotensin II–induced hypertension.⁹ We used a novel telemetry-based implantable amplifier and continuously recorded RSNA before, during, and after 1 week of angiotensin II–based hypertension in rabbits living in their home cages. Angiotensin II infusion (50 ng · kg^–1 · min^–1) caused a sustained increase in arterial pressure and a decrease (45%) in RSNA. Analysis of the baroreflex response showed that although angiotensin II–induced hypertension led to resetting of the mean arterial pressure (MAP)–heart rate relationship, there was no evidence of resetting of the MAP–RSNA relationship. We proposed that the sustained decrease in RSNA during angiotensin II is baroreflex mediated. If this is the case, then we would expect that the decrease in RSNA in response to angiotensin II would not occur in sinoaortic-denervated (SAD) animals. The aim of this study was to determine whether the sympathoinhibitory effect of angiotensin II–induced hypertension is baroreflex dependent.

	Methods

Top Abstract Introduction Methods Results Discussion References

 
Animal Preparation
Experiments were conducted in 12 New Zealand White rabbits with initial weights of 2.4 to 3.5 kg and were approved by the University of Auckland animal ethics committee. Rabbits were housed individually in cages (height 45 cm, width 65 cm, and depth 65 cm) with a telemetry receiver (model RLA2000, Data Sciences International) positioned on the side of each cage. The rabbits were fed daily (100 g standard rabbit pellets, supplemented with hay, carrot, and apple) at 9:00 AM, and water was available ad libitum. The room was kept at a constant temperature (18°C) and light/dark cycle (lights on from 6:00 AM to 6:00 PM).

Rabbits were divided into 2 groups: sham and SAD. Results from the sham (baroreceptor intact) rabbits have been reported previously.⁹ Anesthesia was induced using an intravenous administration of propofol (Diprivan; 10 mg/kg). The rabbits were then intubated and the anesthesia maintained with halothane. All rabbits were instrumented with a radiotelemetry transmitter to record arterial pressure (model PA-D70; Data Sciences International). This was implanted via an abdominal incision, and the area around the iliac bifurcation was exposed. The cannula of the transmitter was inserted into a branch of the left iliac artery and advanced so that the tip of the catheter lay in the abdominal aorta 1 cm above the iliac bifurcation but well below the renal artery. The cannula was tied into position, the body of the transmitter was placed in the abdominal cavity, and the incision was closed. During the same procedure, rabbits also underwent sinoaortic denervation or a sham surgery during which the baroreceptor nerves were exposed but not cut. The aortic depressor nerves were located in the cervical region between the vagus and the sympathetic trunk using a dissecting microscope, separated free, and sectioned near their junction with the superior laryngeal nerve. The carotid sinus nerve was denervated by exposing the carotid sinus region and then cutting all visible nerves between the internal and external carotid arteries and stripping these vessels.

Validation of Arterial Baroreceptor Denervation
Before implantation of the nerve-recording amplifier, the efficacy of the sinoaortic denervation was confirmed. This involved placing the rabbits in a small box within their home cage to allow intravenous lines to be inserted into the medial ear vein and then examining the heart rate responses to a rapid infusion of phenylephrine (200 µL of 1 mg · mL^–1 iv over 30 s) and sodium nitroprusside (100 µL of 1 mg · mL^–1 iv over 30 s). Only animals with a heart rate change of 10 bpm in response to a 20-mm Hg increase or decrease in blood pressure were subsequently considered to be arterial baroreceptor denervated. In sham-operated rabbits, the change in heart rate was between 80 and 100 bpm for a similar change in arterial pressure

At least 2 weeks after the arterial baroreceptor denervation surgery, a telemetry-based implantable nerve amplifier (Model 2003/01; Telemetry Research Ltd) was inserted via a flank incision with the electrodes coiled around the left renal nerve and the electrode and nerve coated in a silicone elastomer (Kwik-sil; World Precision Instruments).⁹ To avoid movement artifacts affecting the RSNA signal, the implantable amplifier was placed as close to the nerve site as possible.

After each surgery, rabbits were treated prophylactically with an antibiotic (enrofloxacin, Baytril; 5 mg/kg sc daily for 5 days) and analgesic (ketoprofen, Ketofen; Rhone Merieux; 2 mg/kg SC daily for 3 days). As soon as the rabbits regained consciousness, they were returned to their home cages. A heating pad was placed in the cage for 24 hours after the surgery.

Data Collection
The rabbits were allowed to recover from surgery to implant the nerve electrodes for 1 week before data collection began. RSNA, blood pressure, and heart rate were then continuously recorded in rabbits before, during, and after a 1-week period of angiotensin II infusion. Thus, after 7 days of baseline data collection, a mini-osmotic pump was implanted (Model 2ML1; Alzet) to continuously infuse angiotensin II at a rate of 50 ng · kg^–1 · min^–1. This osmotic pump was inserted under the same anesthesia protocol as above, with the infusion catheter inserted into the right jugular vein. After 7 days of angiotensin II infusion, the rabbit was removed from its cage, and under brief propofol anesthesia, the mini-osmotic pump was removed.

The recording of arterial pressure and RSNA via telemetry allowed monitoring to take place remotely with rabbits housed in their home cages. RSNA signals were amplified between 10 and 20 000x and bandpass filtered between 50 and 5000 Hz; this signal was used for audibly checking the quality of the recording. The amplified signal was also full-wave rectified and integrated with a time constant of 20 ms. Subsequent analysis was performed on this integrated signal. All data were sampled at 500 Hz using an analog-to-digital data acquisition card (AT-MIO64E-3; National Instruments). All subsequent data collection and analyses were performed using a data acquisition program (Universal acquisition and analysis version 11; Telemetry Research; UniServices Limited) as described previously.⁹

Statistical Analysis
For calculation of the overall mean levels of blood pressure and RSNA, the data were averaged over 2-s periods and saved to disk. All RSNA values were normalized to the mean value of nerve activity recorded on the day before beginning the angiotensin II infusion. All data were analyzed using an ANOVA, with Bonferroni post hoc pairwise comparisons where appropriate. Tests were considered significant if P<0.05. Data are shown as the mean±SEM.

	Results

Top Abstract Introduction Methods Results Discussion References

 
Before angiotensin II infusion, MAP was not significantly different in the sham and SAD rabbits. MAP for the 24-hour period on the day before the angiotensin II infusion began was 82±3 mm Hg in sham rabbits versus 83±3 mm Hg in SAD rabbits. The baroreceptor denervation surgery was shown to be effective with phenylephrine and nitroprusside infusions having little effect on heart rate or RSNA in the SAD rabbits. The SD of the 2-s averages of arterial pressure was significantly greater in the SAD rabbits than the sham rabbits (11±1 mm Hg versus 7±1 mm Hg; P<0.05).

Angiotensin II infusion caused a sustained increase in arterial pressure in the sham and SAD rabbits, with no significant differences in the arterial pressure response between the 2 groups of animals (Figure 1). On day 2 of the infusion, the arterial pressure was 111±4 mm Hg in the SAD rabbits and 102±4 mm Hg in the sham rabbits. Pressure remained elevated for the 7 days of infusion, with the MAP being 100±4 mm Hg in the SAD rabbits and 101±6 mm Hg in the sham rabbits (NS) on the last day of the infusion (Figure 2). Interestingly, in the SAD rabbits, the variability of the pressure increased significantly during the angiotensin II infusion (Figure 3), with the SD of the 2-s averages of arterial pressure being 18±2 mm Hg on day 2 of the infusion (P<0.05 versus before angiotensin II infusion). This increase in arterial pressure variability during angiotensin II was not observed in intact rabbits (the SD of the 2-s averages on day 2 of the angiotensin II infusion in the sham rabbits was 8±1 mm Hg).

View larger version (34K): [in this window] [in a new window]   Figure 1. Mean responses from 6 sham (light line) and 6 SAD rabbits (dark line) to a continuous infusion of angiotensin II for 7 days. Data are presented from the mean value for each 20-minute recording period. Error bars represent the SEM for each day of recording. The angiotensin II infusion began at time 0 and ceased after 7 days, as indicated by the vertical dotted lines. Note: Sham data have been reported previously.9

View larger version (20K): [in this window] [in a new window]   Figure 2. Bar graphs illustrating the mean responses in the 6 sham (open bars) and 6 SAD rabbits (filled bars) on the day before, day 2, day 6, and 3 days after the angiotensin II infusion. MAP was significantly elevated during the angiotensin II infusion in both groups of animals, whereas RSNA was inhibited in only the sham rabbits. *P<0.05 vs before angiotensin II; P<0.05 vs Sham. Note: Sham data have been reported previously.9

View larger version (15K): [in this window] [in a new window]   Figure 3. Arterial pressure from 1 sham and 1 SAD rabbit before and during angiotensin II infusion. Data are shown for a 3-hour period under each condition. The large fluctuation in arterial pressure during angiotensin II infusion was observed in all SAD rabbits.

RSNA did not change in the SAD rabbits with the angiotensin II infusion. This is in contrast to the sham rabbits, in which there was a significant sustained decrease in RSNA. On day 2 of the angiotensin II infusion, RSNA was 98±8% of baseline in the SAD rabbits (NS versus baseline), whereas in the sham rabbits, on day 2, RSNA was 53±7% of baseline (P<0.01 versus baseline and P<0.01 versus SAD). On day 6 of angiotensin II infusion, the RSNA was 103±7% in the SAD and 65±7% of baseline in the sham rabbits. On removal of the angiotensin II pump, all variables recovered to baseline (Figure 2). No significant changes in heart rate were observed (232±6 bpm in the SAD rabbits versus 239±10 bpm in the sham at baseline; NS).

	Discussion

Top Abstract Introduction Methods Results Discussion References

 
We have shown previously that angiotensin II–induced hypertension results in a sustained reduction in RSNA in baroreceptor-intact rabbits.⁹ In the present study, no change in RSNA was observed in SAD rabbits throughout a 7-day period of angiotensin II–induced hypertension. These results suggest that the sympathoinhibitory action of angiotensin II on RSNA in baroreceptor-intact animals is dependent on an intact arterial baroreceptor reflex.

The factors that chronically influence sympathetic activity remain unclear, in part because of the technical limitations that have prevented sympathetic activity to be assessed chronically. Our laboratory has addressed this issue by developing a technique for chronically recording sympathetic activity via telemetry.⁹ The present study is the first to show directly that RSNA is inhibited in response to angiotensin II–induced hypertension in intact but not barodenervated animals. The possibility that the arterial baroreflexes may not be resetting but playing a role in long-term pressure control by having a sustained influence on RSNA is controversial. The general consensus is that baroreflexes reset in response to maintained changes in arterial pressure and thus cannot be important in setting the long-term level of pressure. However, a growing number of reports suggest that baroreflex control of RSNA may not reset as rapidly as suggested previously.^5,6,10,11 We have clearly shown that arterial baroreflex control of RSNA does not reset within a 7-day period of angiotensin II infusion, suggesting that the arterial baroreflex is not just a reflex concerned with the second-to-second control of arterial pressure but may be able to influence arterial pressure over much longer time periods. Whether the baroreflex would reset if the increase in pressure was maintained for a longer period is not clear. In a 2-kidney, 1-clip model of hypertension in rabbits, RSNA (compared between animals) appeared to be reset by a similar degree as the increase in pressure after 3 weeks, although the range of reflex was attenuated, whereas 6 weeks after the clipping, the range was similar to that observed before the clipping.¹² It is possible that we would have seen resetting in our angiotensin II–induced hypertension model had the hypertension been maintained for >7 days.

It is well recognized that hypertension is associated with elevated sympathetic nerve activity, in particular to the heart and kidneys.^13,14 The mechanisms that lead to increases in sympathetic activity are not entirely clear, although baroreflex dysfunction,^2,15,16 central actions of angiotensin II,^17–19 and leptin in the case of obesity-associated hypertension²⁰ are just some of the contenders. Our results show that at a pressor dose, angiotensin II is actually sympathoinhibitory, suggesting that the arterial baroreflexes are attempting to counter the angiotensin II–induced increase in arterial pressure. Does this mean that arterial pressure would be even higher in the face of impaired baroreflex function? The present results suggest not; despite the difference in nerve activity between the baroreceptor-intact and -denervated animals, the arterial pressure response to angiotensin II was not significantly different. The lack of a difference in pressure between the 2 groups of rabbits suggests that the level of RSNA is not a critical factor in setting the mean level of arterial pressure in this setting. The control of arterial pressure is dependent on a number of neural, hormonal, and local factors, and in terms of long-term pressure regulation, there clearly are mechanisms that are capable of overriding the effects of a decrease in RSNA. Such mechanisms include the direct effect of angiotensin II on the vasculature and pressure-natriuresis.

The increased variability in arterial pressure observed in the baroreceptor-denervated rabbits during the angiotensin II–induced hypertension is an illustration of the importance of the arterial baroreflex in buffering rapid changes in arterial pressure. The increase in variability was only observed in the SAD rabbits, thus exemplifying that there is redundancy in the arterial pressure control system; when >1 pressure control system is compromised, the role of the baroreflexes becomes especially evident (ie, the importance of the baroreflex in buffing the rapid changes in pressure is most evident in the presence of baroreceptor denervation and high angiotensin II levels). A similar phenomenon is seen with salt loading; a combination of salt loading and baroreceptor denervation is known to cause hypertension in rats, whereas either treatment alone has no effect on the mean pressure level.^21,22 During angiotensin II infusion, the pressure in the SAD rabbits was clearly not normal, with the large fluctuations resulting in extreme high and low pressures. The increased pressure variability in barodenervated animals is known to be associated with significant end-organ damage in the heart^23,24 and kidneys,^25,26 illustrating the importance of the baroreflexes in maintaining a suitable perfusion pressure.

The model of hypertension used in these experiments is based on a pressor dose of angiotensin II (50 ng · kg^–1min^–1), with arterial pressure rising rapidly, but within a physiological range (20 mm Hg). We cannot completely discount the possibility that the sympathoinhibition we observed in the baroreceptor-intact animals may be specific to either angiotensin II itself or the dose used. Short-term neural recordings and indirect measures of sympathetic activity, such as ganglionic blockade, have tended to suggest that angiotensin II is sympathoexcitatory.^19,27 Studies looking at Fos expression during angiotensin II infusion have also produced contradictory results, with reports of increased Fos expression in the rostral ventral lateral medulla in the rat²⁸ but no change in the dog.²⁹ It is unclear whether these differences are attributable to differences in length or dose of angiotensin II infusion or a species difference; however, there does seem to be a need to explore the effect of angiotensin II at different doses.

Perspectives
Renal function is well recognized to be central to long-term control of arterial pressure. There is strong evidence to suggest that RSNA is activated in the developmental phase of hypertension and thus may play a causal role in the pathogenesis of hypertension.^30,31 Our results suggest that in the presence of an intact arterial baroreceptor reflex, we would expect to see a sustained sympathoinhibition in response to an increase in arterial pressure. Depressed baroreflex function is not an uncommon finding in hypertension^2,15,16 and would certainly help explain the sympathoexcitation seen in hypertension. Such baroreflex dysfunction would put such persons not only at risk of developing hypertension but also an increase in arterial pressure variability, which, in itself, is likely to have cardiovascular consequences, and thus the role of the baroreflexes in long-term control of arterial pressure cannot be ignored.

	Acknowledgments

 
This work was supported by grants from the Auckland Medical Research Foundation, Health Research Council of New Zealand, Lottery Grants, and Maurice and Phyllis Paykel Trust.

Received January 18, 2005; first decision February 8, 2005; accepted April 16, 2005.

	References

Top Abstract Introduction Methods Results Discussion References

 
1. Guyton AC, Hall JE. Textbook of Medical Physiology. 9th ed. Philadelphia, Pa: W.B. Saunders Company; 1996.

2. McCubbin JW, Green JH, Page IH. Baroreceptor function in chronic renal hypertension. Clin Res. 1956; 4: 205–210.[Medline] [Order article via Infotrieve]

3. Cowley AW Jr, Liard JF, Guyton AC. Role of baroreceptor reflex in daily control of arterial blood pressure and other variables in dogs. Circ Res. 1973; 32: 564–576.[Abstract/Free Full Text]

4. Cowley AW Jr. Long-term control of arterial blood pressure. Physiol Rev. 1992; 72: 231–300.[Abstract/Free Full Text]

5. Lohmeier TE, Lohmeier JR, Haque A, Hildebrandt DA. Baroreflexes prevent neurally induced sodium retention in angiotensin hypertension. Am J Physiol Regul Integr Comp Physiol. 2000; 279: R1437–R1448.[Abstract/Free Full Text]

6. Thrasher TN. Unloading arterial baroreceptors causes neurogenic hypertension. Am J Physiol Regul Integr Comp Physiol. 2002; 282: R1044–1053.[Abstract/Free Full Text]

7. Greenwood JP, Stoker JB, Mary DA. Single-unit sympathetic discharge: quantitative assessment in human hypertensive disease. Circulation. 1999; 100: 1305–1310.[Abstract/Free Full Text]

8. Esler M, Jennings G, Lambert G, Meredith I, Horne M, Eisenhofer G. Overflow of catecholamine neurotransmitters to the circulation: source, fate, and functions. Physiol Rev. 1990; 70: 963–985.[Free Full Text]

9. Barrett CJ, Ramchandra R, Guild SJ, Lala A, Budgett DM, Malpas SC. What sets the long-term level of renal sympathetic nerve activity: a role for angiotensin II and baroreflexes? Circ Res. 2003; 92: 1330–1336.[Abstract/Free Full Text]

10. Carroll RG, Lohmeier TE, Brown AJ. Chronic angiotensin II infusion decreases renal norepinephrine overflow in conscious dogs. Hypertension. 1984; 6: 675–681.[Abstract/Free Full Text]

11. Lohmeier TE, Hildebrandt DA, Hood WA. Renal nerves promote sodium excretion during long-term increases in salt intake. Hypertension. 1999; 33: 487–492.[Abstract/Free Full Text]

12. Head GA, Burke SL. Renal and cardiac sympathetic baroreflexes in hypertensive rabbits. Clin Exp Pharmacol Physiol. 2001; 28: 972–975.[CrossRef][Medline] [Order article via Infotrieve]

13. Esler M, Jennings G, Lambert G. Noradrenaline release and the pathophysiology of primary human hypertension. Am J Hypertens. 1989; 2: 140S–146S.[Medline] [Order article via Infotrieve]

14. Esler M, Lambert G, Jennings G. Increased regional sympathetic nervous activity in human hypertension: causes and consequences. J Hypertens Suppl. 1990; 8: S53–57.[CrossRef][Medline] [Order article via Infotrieve]

15. Head GA. Cardiac baroreflexes and hypertension. Clin Exp Pharmacol Physiol. 1994; 21: 791–802.[Medline] [Order article via Infotrieve]

16. Mancia G, Di Rienzo M, Parati G, Grassi G. Sympathetic activity, blood pressure variability and end organ damage in hypertension. J Hum Hypertens. 1997; 11 (suppl 1): S3–S8.[Medline] [Order article via Infotrieve]

17. Cox BF, Bishop VS. Neural and humoral mechanisms of angiotensin-dependent hypertension. Am J Physiol Heart Circ Physiol. 1991; 261: H1284–291.[Abstract/Free Full Text]

18. Fink GD. Long-term sympatho-excitatory effect of angiotensin II: a mechanism of spontaneous and renovascular hypertension. Clin Exp Pharmacol Physiol. 1997; 24: 91–95.[Medline] [Order article via Infotrieve]

19. Li Q, Dale WE, Hasser EM, Blaine EH. Acute and chronic angiotensin hypertension: neural and nonneural components, time course, and dose dependency. Am J Physiol Regul Integr Comp Physiol. 1996; 271: R200–R207.[Abstract/Free Full Text]

20. Hall JE, Hildebrandt DA, Kuo J. Obesity hypertension: role of leptin and sympathetic nervous system. Am J Hypertens. 2001; 14: 103S–115S.[CrossRef][Medline] [Order article via Infotrieve]

21. Osborn JW, Hornfeldt BJ. Arterial baroreceptor denervation impairs long-term regulation of arterial pressure during dietary salt loading. Am J Physiol Heart Circ Physiol. 1998; 275: H1558–H1566.[Abstract/Free Full Text]

22. Howe PR, Rogers PF, Minson JB. Influence of dietary sodium on blood pressure in baroreceptor-denervated rats. J Hypertens. 1985; 3: 457–460.[Medline] [Order article via Infotrieve]

23. Tao X, Zhang SH, Chu ZX, Su DF. Apoptosis is involved in the cardiac damage induced by sinoaortic denervation in rats. Clin Exp Pharmacol Physiol. 2003; 30: 362–368.[CrossRef][Medline] [Order article via Infotrieve]

24. Van Vliet BN, Hu L, Scott T, Chafe L, Montani JP. Cardiac hypertrophy and telemetered blood pressure 6 wk after baroreceptor denervation in normotensive rats. Am J Physiol Regul Integr Comp Physiol. 1996; 271: R1759–R1769.[Abstract/Free Full Text]

25. Shan ZZ, Dai SM, Su DF. Relationship between baroreceptor reflex function and end-organ damage in spontaneously hypertensive rats. Am J Physiol Heart Circ Physiol. 1999; 277: H1200–H1206.[Abstract/Free Full Text]

26. Shan ZZ, Dai SM, Su DF. Arterial baroreflex deficit induced organ damage in sinoaortic denervated rats. J Cardiovasc Pharmacol. 2001; 38: 427–437.[CrossRef][Medline] [Order article via Infotrieve]

27. Luft FC, Wilcox CS, Unger T, Kuhn R, Demmert G, Rohmeiss P, Ganten D, Sterzel RB. Angiotensin-induced hypertension in the rat. Sympathetic nerve activity and prostaglandins. Hypertension. 1989; 14: 396–403.[Abstract/Free Full Text]

28. Li Q, Sullivan MJ, Dale WE, Hasser EM, Blaine EH, Cunningham JT. Fos-like immunoreactivity in the medulla after acute and chronic angiotensin II infusion. J Pharmacol Exp Ther. 1998; 284: 1165–1173.[Abstract/Free Full Text]

29. Lohmeier TE, Lohmeier JR, Warren S, May PJ, Cunningham JT. Sustained activation of the central baroreceptor pathway in angiotensin hypertension. Hypertension. 2002; 39: 550–556.[Abstract/Free Full Text]

30. Anderson EA, Sinkey CA, Lawton WJ, Mark AL. Elevated sympathetic nerve activity in borderline hypertensive humans. Evidence from direct intraneural recordings. Hypertension. 1989; 14: 177–183.[Abstract/Free Full Text]

31. Floras JS, Hara K. Sympathoneural and hemodynamic characteristics of young subjects with mild essential hypertension. J Hypertens. 1993; 11: 647–655.[CrossRef][Medline] [Order article via Infotrieve]

This article has been cited by other articles:

				H. C. Hercule, J. Tank, R. Plehm, M. Wellner, A. C. da Costa Goncalves, M. Gollasch, A. Diedrich, J. Jordan, F. C. Luft, and V. Gross Cardiovascular Control: Regulator of G protein signalling 2 ameliorates angiotensin II-induced hypertension in mice Exp Physiol, November 1, 2007; 92(6): 1014 - 1022. [Abstract] [Full Text] [PDF]

				F. D. McBryde, S.-J. Guild, C. J. Barrett, J. W. Osborn, and S. C. Malpas Cardiovascular Control: Angiotensin II-based hypertension and the sympathetic nervous system: the role of dose and increased dietary salt in rabbits Exp Physiol, September 1, 2007; 92(5): 831 - 840. [Abstract] [Full Text] [PDF]

				A. J. King, J. W. Osborn, and G. D. Fink Splanchnic Circulation Is a Critical Neural Target in Angiotensin II Salt Hypertension in Rats Hypertension, September 1, 2007; 50(3): 547 - 556. [Abstract] [Full Text] [PDF]

				R. Ramchandra, C. J. Barrett, S.-J. Guild, F. McBryde, and S. C. Malpas Role of renal sympathetic nerve activity in hypertension induced by chronic nitric oxide inhibition Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2007; 292(4): R1479 - R1485. [Abstract] [Full Text] [PDF]

				J. T. Cunningham, M. Herrera-Rosales, M. A. Martinez, and S. Mifflin Identification of Active Central Nervous System Sites in Renal Wrap Hypertensive Rats Hypertension, March 1, 2007; 49(3): 653 - 658. [Abstract] [Full Text] [PDF]

				V. L. Brooks, K. L. Freeman, and Y. Qi Time course of synergistic interaction between DOCA and salt on blood pressure: roles of vasopressin and hepatic osmoreceptors Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2006; 291(6): R1825 - R1834. [Abstract] [Full Text] [PDF]

				P. B. Persson Baroreflexes in Hypertension: A Mystery Revisited Hypertension, November 1, 2005; 46(5): 1095 - 1096. [Full Text] [PDF]

This Article Abstract Full Text (PDF) All Versions of this Article: 46/1/168    most recent 01.HYP.0000168047.09637.d4v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Barrett, C. J. Articles by Malpas, S. C. Search for Related Content PubMed PubMed Citation Articles by Barrett, C. J. Articles by Malpas, S. C. Related Collections Hypertension - basic studies Autonomic, reflex, and neurohumoral control of circulation