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This article cites 38 articles, 21 of which you can access free at:
http://jap.physiology.org/cgi/content/full/97/5/1746#BIBL
This article has been cited by 12 other HighWire hosted articles, the first 5 are:
Enhanced angiotensin-mediated excitation of renal sympathetic nerve activity within the
paraventricular nucleus of anesthetized rats with heart failure
H. Zheng, Y.-F. Li, W. Wang and K. P. Patel
Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2009; 297 (5): R1364-R1374.
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Journal of Applied Physiology publishes original papers that deal with diverse areas of research in applied physiology, especially
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Physiological Society, 9650 Rockville Pike, Bethesda MD 20814-3991. Copyright © 2004 by the American Physiological Society.
ISSN: 8750-7587, ESSN: 1522-1601. Visit our website at http://www.the-aps.org/.
J Appl Physiol 97: 1746 –1754, 2004;
doi:10.1152/japplphysiol.00573.2004.
Zhu, Guo-Qing, Lie Gao, Kuashik P. Patel, Irving H. Zucker, denervated dogs with CHF (6, 18). Therefore, a blunted sym-
and Wei Wang. ANG II in the paraventricular nucleus potentiates the pathoinhibitory reflex does not completely explain the chronic
cardiac sympathetic afferent reflex in rats with heart failure. J Appl elevation in sympathetic outflow in the CHF state. It has been
Physiol 97: 1746 –1754, 2004; doi:10.1152/japplphysiol.00573. shown that the cardiac sympathetic afferent reflex (CSAR) is
2004.—Chronic heart failure (CHF) is characterized by sympathoex- sympathoexcitatory and contributes to the sympathoexcitation
citation, and the cardiac sympathetic afferent reflex (CSAR) is a
in dogs with CHF (24, 32). The pathways of this reflex may be
sympathoexcitatory reflex. Our previous studies have shown that the
CSAR was enhanced in CHF. In addition, central angiotensin II (ANG similar to those involved in signaling cardiac pain during acute
II) is an important modulator of this reflex. This study was performed ischemia (11, 23). This positive-feedback mechanism may be
to determine whether the CSAR evoked by stimulation of cardiac deleterious in the CHF state over the long term. Previous
1746 8750-7587/04 $5.00 Copyright © 2004 the American Physiological Society http://www. jap.org
CARDIAC SYMPATHETIC AFFERENT REFLEX IN RATS 1747
METHODS system with other parameters. A voltage integrator (model 1801,
Buxco Electronics, Sharon, CT) was used for quantifying the raw
Male Sprague-Dawley rats weighing between 350 and 420 g were renal sympathetic nerve activity (RSNA). Background noise was
used in the experiments. All experiments were approved by the determined when nerve activity was completely inhibited by increas-
Institutional Animal Care and Use Committee of the University of ing arterial pressure (phenylephrine 20 g/kg iv) before sinoarotic
Nebraska and were carried out under the guidelines of the American denervation or after section of the central end of the renal nerve at the
Physiological Society and the National Institutes of Health Guide for end of the experiment. This value was subtracted from all the
the Care and Use of Laboratory Animals. integrated values of RSNA. The raw nerve activity, integrated nerve
activity, arterial pressure, and HR were recorded on a PowerLab data
Model of CHF acquisition system (model 16S, ADInstruments, Mountain View, CA)
and stored on disk until analyzed.
CHF was produced by coronary artery ligation as previously The chest was opened through the left second intercostal space. The
described (26, 35). All rats were anesthetized with pentobarbital left ventral ansa, which contains cardiac sympathetic afferent nerves
sodium (50 mg/kg ip) and instrumented with sterile techniques. The was identified, tied, and ligated. A pair of stainless steel stimulating
trachea was cannulated to facilitate mechanical ventilation. A left electrodes was placed on the central end of this nerve. The stimulus
thoracotomy was performed through the fifth intercostal space. After was delivered with a stimulator (model S88, Grass, West Warwick,
retraction of the lung, the pericardium was opened to expose the heart. RI) and a stimulus isolation unit. The frequencies of stimulation
The left coronary artery was ligated by using 6-0 suture near its varied at 5, 10, 20, and 30 Hz at a constant voltage of 10 V. The pulse
branch point from the aorta, between the pulmonary artery outflow width was kept at 1 ms, and each stimulus train lasted 30 s. Stimuli
tract and left atrium. After these maneuvers, the heart was placed in its were delivered in random sequences in each experimental protocol.
original position and the thorax was closed. The air within the thorax The time period between each stimulus was 1–2 min.
was evacuated, allowing the rats to resume spontaneous respiration
RESULTS
n 20 30
Response to ANG II in the PVN After Pretreatment
BW, g 412.4⫾5.2 407.6⫾4.3 With Losartan
HW, g 1.32⫾0.03 1.65⫾0.03*
HW/BW, g/kg 3.21⫾0.06 4.06⫾0.08* To determine the contribution of AT1 receptors to the
IS, %LV area 0 33.7⫾1.9* enhanced response to stimulation in CHF rats, losartan was
SAP, mmHg 115.2⫾4.0 95.9⫾2.4* unilaterally microinjected into the PVN before measurment of
DAP, mmHg 66.9⫾3.5 70.5⫾2.7 the effect of administration of ANG II into the PVN. As shown
PP, mmHg 48.3⫾3.2 25.4⫾1.9*
MAP, mmHg 85.0⫾3.4 82.0⫾2.5
in Fig. 5, losartan abolished the effect of ANG II. There were
HR, beats/min 334.6⫾18.2 388.9⫾9.4* no significant differences between the saline group and losartan
LVSP, mmHg 126.2⫾5.3 99.5⫾4.1* plus ANG II group.
LVEDP, mmHg 1.6⫾0.7 15.5⫾1.1*
dP/dtmax, mmHg/s 3,497⫾94 1,894⫾97* Unilateral Microinjection of ANG II into the PVN in Sham
Values are as means ⫾ SE; n, no. of animals. BW, body weight; HW, heart
and CHF Rats
weight; IS, Infarct size; LV, left ventricle; SAP, systolic arterial pressure;
DAP, diastolic arterial pressure; PP, pulse pressure; MAP, mean arterial
Three doses of ANG II (0.03, 0.3, and 3 nmol) or saline were
pressure; LVSP, LV peak systolic pressure; LVEDP, LV end-diastolic pres- microinjected into the PVN in rats with CHF. Figure 6 shows
38. Zhu GQ, Patel KP, Zucker IH, and Wang W. Microinjection of ANG 40. Zucker IH and Wang W. Reflex control of renal sympathetic nervous
II into paraventricular nucleus enhances cardiac sympathetic afferent activity in heart failure. Herz 16: 82–91, 1991.
reflex in rats. Am J Physiol Heart Circ Physiol 282: H2039 –H2045, 2002. 41. Zucker IH, Wang W, Pliquett RU, Liu JL, and Patel KP. The
39. Zhu GQ, Zucker IH, and Wang W. Central AT1 receptors are involved regulation of sympathetic outflow in heart failure. The roles of angiotensin
in the enhanced cardiac sympathetic afferent reflex in rats with chronic II, nitric oxide, and exercise training. Ann NY Acad Sci 940: 431– 443,
heart failure. Basic Res Cardiol 97: 320 –326, 2002. 2001.