(Hypertension. 1996;27:36-42.)
© 1996 American Heart Association, Inc.
Articles |
Cardiovascular Effects of Nitric Oxide in the Brain Stem Nuclei of Rats
From the Department of Medical Education and Research, Veterans General Hospital–Kaohsiung (C.-J.T., L.-P.G.), and Departments of Pharmacology (C.-J.T., H.-Y.L., H.-C.L., M.-H.Y.) and Physiology and Biophysics (C.-S.T.), National Defense Medical Center, Taipei, Taiwan, Republic of China.
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Abstract |
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 Top Abstract IntroductionMethods Results Discussion References |
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Abstract Nitric oxide, synthesized from the semiessential amino acid L-arginine by nitric oxide synthase, is a remarkable regulatory molecule and plays an important role in physiological functions. However, the physiological role of nitric oxide in cardiovascular regulation by the central nervous system is not well understood. In this study we investigated the cardiovascular effects of nitric oxide in the lateral ventricle, nucleus tractus solitarii, area postrema, and rostral ventrolateral medulla in urethane-anesthetized male Sprague-Dawley rats. Microinjection of NG-monomethyl-L-arginine, a nitric oxide synthase inhibitor, into the cerebral ventricle of rats elicited a dose-dependent increase in blood pressure and heart rate. This suggests that nitric oxide may be involved in central cardiovascular regulation. Unilateral microinjection (60 nL) of L-arginine (1 to 100 nmol) into the nucleus tractus solitarii and rostral ventrolateral medulla produced prominent dose-related depressor and bradycardic effects and reduced renal sympathetic nerve activity. However, L-arginine had no significant cardiovascular effects in the area postrema. In addition, 4 to 6 hours after intravenous injection of bacterial endotoxin-lipopolysaccharide (10 mg/kg), there was a time-related potentiation of the L-arginine–induced depressor and bradycardic effects in the nucleus tractus solitarii. These results indicate that nitric oxide is involved in central cardiovascular regulation. The depressor effect of nitric oxide in the nucleus tractus solitarii and rostral ventrolateral medulla may be through inhibition of renal sympathetic nerve activity.
Key Words: nitric oxide • arginine • L-NMMA • lipopolysaccharide • central nervous system
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Introduction |
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TopAbstractIntroductionMethods Results Discussion References |
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Since the determination that endothelium-derived relaxing factor is NO,1 2 NO has been reported as both a second messenger and neurotransmitter and has been implicated in an extraordinarily diverse range of physiological functions.3 4 5 NO is synthesized from arginine in endothelial cells in response to various physiological stimuli.6 7
Numerous studies indicate that NO is the major physiological regulator of basal blood vessel tone.5 8 9 The systemic administration of NG-methyl arginine (L-NMA), a competitive inhibitor of NO synthesis from arginine, elicits a sustained increase in arterial BP in all species examined,5 10 11 indicating that basal NO release from peripheral resistance vessels is responsible for a continuous vasorelaxant action in vivo. Administration of NOS inhibitors in vivo has been shown to result in constriction and decreased conductance of various vascular beds in the rat.9
Clinical studies have reported that atherosclerosis, hypertension, and hypoxia are related to the NO system12 13 and that NOS inhibitors may play a role in some cardiovascular regulation. The participation of NO in the maintenance of vascular tone in various tissues has been shown to result from nonadrenergic, noncholinergic nerves14 15 via cholinergic stimulation16 and in response to shear stress.17 Immunohistochemical localization of NOS shows it to be exclusively localized to discrete neuronal populations throughout the brain.18 Furthermore, NO decreases central sympathetic outflow19 and mediates L-glutamate–elicited decreases in BP and HR through baroreceptor-like reflexes in the NTS.20 Tagawa et al21 also reported recently that NO increases the neuronal activity of adjacent neurons in the NTS through an increase in cGMP. However, the cardiovascular effects of NO in relevant important brain stem nuclei such as the NTS, RVLM, and AP remain unclear.
In the present study we characterized the central hemodynamic response of L-Arg and NOS inhibitor administration into the NTS, AP, and RVLM of normotensive rats. In addition, we investigated the relevance of sympathetic mechanisms for the cardiovascular effects of NO in the brain stem nuclei.
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Methods |
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TopAbstractIntroductionMethods Results Discussion References |
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Male Sprague-Dawley rats (250 to 300 g) were obtained and housed in the animal room of the National Defense Medical Center (Taipei, Taiwan, ROC). The rats were kept in individual cages in a room where lighting was controlled (12 hours on, 12 hours off) and temperature was kept between 23° and 24°C. The rats were given Purina Laboratory Chow and tap water ad libitum.
Rats were anesthetized with urethane (1.0 g/kg IP, supplemented with 300 mg/kg IV if necessary). A polyethylene cannula was placed in the femoral vein for drug administration. BP was measured directly through a cannula placed in the femoral artery and connected to a pressure transducer (Gould P23 ID) and polygraph (Gould RS3800). HR was monitored continuously by a tachograph preamplifier (Gould 13-4615-65). Tracheostomy was performed to maintain airway patency during the experiment.
For intracerebroventricular administration of drugs, a 22-gauge stainless steel guide cannula was implanted stereotaxically into the lateral cerebral ventricle according to the stereotaxic atlas of Paxinos and Watson.22 Through this cannula a 28-gauge stainless steel injection cannula was inserted into the lateral ventricles (medial-lateral: 1.5 mm; rostral-caudal: -0.8 mm; dorsal-ventral: -3.7 mm; with bregma as reference). Drugs were dissolved in sterile saline to the final concentrations in a volume of 5 µL, and the same volume was injected. The position of the injection cannula was verified at the end of the experiments by injection of 5 µL 2-bromphenol blue solution and examination of ventricular stain postmortem.
For brain stem nuclei microinjection the rats were placed in a stereotaxic instrument (Kopf), with the head flexed downward at a 45° angle. The dorsal surface of the medulla was exposed by limited craniotomy, and the rats were rested for at least 1 hour before experiments. Single-barrel glass cannulas were prepared (0.031-inch OD, 0.006-inch ID; Richland Glass Co) that had external tip diameters of 40 µm. The cannula was connected to a Hamilton microsyringe by polyvinyl tubing. The cannulas were filled with L-glutamate (78 pmol/60 nL, to functionally identify the NTS and RVLM; see below), adenosine (2.3 nmol/60 nL, for identification of the AP), or different doses of L-Arg and NOS inhibitors. The cannula was lowered into the NTS with the anteroposterior coordinates 0.0 mm; mediolateral, 0.5 mm; and vertical, 0.4 mm; into the AP with anteroposterior coordinates +0.5 mm; mediolateral, 0.0 mm; and vertical; 0.2 mm; or into the RVLM with anteroposterior coordinates, 2.5 mm; mediolateral, 2.0 mm; and vertical, 2.6 mm, with the obex as reference.23 24 25
During the experiment the NTS injection sites were confirmed by responsiveness to L-glutamate administration. A specific decrease in BP and HR (at least -35 mm Hg and -50 bpm, respectively) has been demonstrated after microinjection of 2.3 nmol L-glutamate in the NTS.26 The response is restricted to the intermediate one third of the NTS, and the administration of the same dose of L-glutamate in adjacent areas to the NTS fails to elicit the response. In agreement with our previous study23 and other reports,26 we did not observe significant effects on mean BP or HR after the administration of 60 nL sterile saline in the NTS, AP, or RVLM; therefore, we used saline for the control experiments in this study.
To elucidate the effects of L-Arg and NOS inhibitors in sympathetic outflow, rats were instrumented for recording of RSNA. In brief, a left-sided laparotomy was performed to expose the left renal nerve at the junction of the renal artery and aorta. The nerve was carefully dissected and placed in situ on bipolar hook electrodes (0.003-inch polytetrafluoroethylene-insulated stainless steel, Medwire Corp). The site was covered with low-viscosity polyvinylsiloxane dental impression material to electrically isolate the nerve-electrode junction. Multiunit recordings were amplified approximately 100 000 times in two stages by an isolated preamplifier (Gould 11-5407-58) and universal amplifier (Gould 13-4615-58). Nerve activity was full-wave rectified, integrated, and expressed in arbitrary units proportional to volts-second by an integrator amplifier (Gould 13-4615-70). Total RSNA (equal to the sum of efferent and afferent activities plus electrical noise) was recorded, and the signal remaining after intravenous administration of hexamethonium (20 mg/kg) was assumed to represent electrical noise and afferent activity. The magnitude of this signal was considered to be an estimate of zero efferent nerve activity, and estimates of efferent nerve activity were obtained by subtracting zero activity from the total recorded activity.
After completion of the experiment ink was injected through the
cannula, and the rats were perfused with saline, followed by a solution
of 4% formaldehyde and finally a 30% sucrose solution. Sections of 40
µm of the brain stem were stained with cresyl violet, and proper
placement of the pipette tip in the AP, NTS, and RVLM was verified by
examination of the sections under the microscope. A diagrammatic
representation of some individual injection sites in the
Sprague-Dawley rat are shown in Fig 1
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Drugs for microinjection were dissolved so that the desired amount of drug was contained in 60 nL. The following drugs were used: urethane (Aldrich Chemical Co), L-glutamic acid, adenosine, L-Arg, hexamethonium HCl, and L-NMMA (Sigma Chemical Co).
For statistical analysis paired Student's t test (before and after NTS, AP, or RVLM microinjection) and unpaired t test (for control and study group comparisons) or ANOVA followed by Dunnett's test for significant differences was used. Differences with a probability value less than .05 were taken as significant. All data are presented as mean±SEM.
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Results |
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TopAbstractIntroductionMethods Results Discussion References |
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Cardiovascular Effects of L-Arg or L-NMMA in the Lateral Ventricle
In agreement with other researchers19 microinjection of different doses of the NOS inhibitor L-NMMA into the lateral ventricle produced dose-dependent pressor and tachycardic effects (Fig 2
). Microinjection of 10 nmol L-NMMA
significantly attenuated the cardiovascular effects of
L-Arg. Similar effects were observed in conscious rats.
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indicates changes of MAP;
, changes of HR. Each point represents the average of
eight rats. *P<.05 (paired t test) compared with
control value.
Cardiovascular Effects of L-Arg and L-NMMA in
the NTS
Unilateral microinjection of ascending doses of L-Arg (10, 33,
and
100 nmol) into the NTS produced dose-dependent depressor and
bradycardic effects (Fig 3). The depressor effect
reached a maximum at 33 nmol. As the L-Arg doses increased to more than
100 nmol, there was a tendency for HR and respiration to be inhibited
and cause sudden death. As shown in Fig 4 microinjection
of 100 nmol L-Arg into the NTS produced depressor and bradycardic
effects, with concomitant decreases in RSNA. The bottom trace shows
clearer inhibition of the integrated RSNA, which was found with all
doses tested.
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On the contrary, unilateral microinjection of ascending
doses of L-NMMA
into the NTS produced dose-dependent pressor and bradycardic
effects (Fig 5). During the period of pressor effect,
RSNA increased significantly (Fig 6).
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To support the
specificity of the cardiovascular
effects of L-Arg, we used a selective NOS inhibitor. As
demonstrated in Figs 7 and 8 unilateral
microinjection of 10 nmol L-Arg into the NTS produced depressor and
bradycardic effects. Earlier microinjection of L-NMMA (10 nmol)
partially attenuated the cardiovascular effects of
L-Arg, and 33 nmol L-NMMA almost completely inhibited the
cardiovascular effects of L-Arg. The depressor and
bradycardic effects reappeared 60 minutes after microinjection of
L-NMMA.
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Cardiovascular Effects of L-Arg and L-NMMA in
the AP
The AP is a tissue very close to the NTS. However,
microinjection
of different doses of L-Arg (10, 33, and 100 nmol) or L-NMMA (33 and
100 nmol) into the AP did not produce any significant change in
cardiovascular effects (data not shown).
Cardiovascular Effects of L-Arg and L-NMMA in
the RVLM
Similar to the cardiovascular effects of L-Arg and
L-NMMA in the NTS, microinjection of L-Arg into the RVLM produced
dose-dependent depressor and bradycardic effects and inhibition of
RSNA (Figs 9 and 10). L-NMMA
administration into the RVLM produced pressor and tachycardic effects
and increases of RSNA (Fig 11). Prior administration of
33 nmol L-NMMA significantly attenuated the
cardiovascular effects of L-Arg (Fig 12).
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Induction of NOS in the NTS
We used bacterial
endotoxin-lipopolysaccharide in
this study to induce the formation of inducible NOS. The depressor and
bradycardic effects of L-Arg in the NTS were significantly potentiated
4 or 5 hours after intravenous administration of 10 mg/kg
lipopolysaccharide (Fig 13). These data
indicate that there is more inducible NOS being activated by
lipopolysaccharide.
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Discussion |
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TopAbstractIntroductionMethods Results Discussion References |
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The NO system seems to play an important role in the regulation of cardiovascular responses. In the present study we observed that intracerebroventricular injection of L-NMMA produced dose-dependent pressor and tachycardic effects similar to the findings of Togashi et al.19 We also observed that prior microinjection of L-Arg can reverse the pressor effect of L-NMMA, further indicating that the central effect of L-NMMA was through a reversible mechanism of L-Arg. However, based on this data we still did not know the precise site of the cardiovascular action of the NO system. Immunohistochemical study already has confirmed that NOS is distributed in cortex, cerebellum, brain stem, and other brain areas.27 Administration of L-NMMA into the cisternal magna produced a pressor effect,28 which made us interested in investigating the role of NO in cardiovascular regulation in brain stem nuclei.
Microinjection of L-Arg into the NTS elicited dose-dependent depressor and bradycardic effects and inhibited RSNA. This suggests that L-Arg was transferred into NO by NOS present in the NTS. The newly formed NO diffused into presynaptic terminals or neighboring astrocytes to activate guanylate cyclase, causing the accumulation of cGMP. In the nervous system cGMP can act directly on ionic channels; for example, sodium and calcium ions increase the firing rate of the ionic channels; cGMP also can act on specific protein kinase29 and phosphodiesterase30 to facilitate the formation of cGMP. The increased calcium influx activates the neurons and receptors of excitatory amino acid, which causes the decrease in BP, HR, and RSNA. Our results are similar to the report of Lewis et al31 that microinjection of the endothelium-derived relaxing factor analogue S-nitrosocysteine into the NTS produced dose-dependent depressor and bradycardic effects.
Unilateral microinjection of the NOS inhibitor L-NMMA into the NTS produced dose-dependent bradycardic effects. However, this bradycardic effect was inhibited after intravenous injection of atropine, indicating that the bradycardic effect after L-NMMA was due to the baroreflex. Effects of a low dose (10 nmol) and high doses (33 and 100 nmol) on BP differed. Microinjection of 10 nmol L-NMMA produced a decrease in BP, and high doses produced a pressor effect. We hypothesize that during low-dose L-NMMA, the activity of constitutive NOS was abolished, whereas the inducible NOS activity was still present in the NTS. Therefore, L-Arg can be transferred into NO by inducible NOS and then cause a depressor effect as described in the previous mechanism. To test this hypothesis we used intravenous injection of lipopolysaccharide to activate the inducible NOS. We found that 4 to 6 hours after induction, there seemed to be an elevation of inducible NOS activity in the central nervous system and attenuation of the reverse effect of L-NMMA on the bradycardic effect of L-Arg. A high dose of L-NMMA inhibited almost all of the constitutive and inducible NOS in the NTS that cause a pressor effect.
Our study in the AP demonstrated completely different responses. BP and HR did not change significantly after microinjection of L-Arg or L-NMMA into the AP. These results are similar to a study in rabbit which indicated that L-Arg injection into the AP did not produce any change in BP and HR.32 We suggest that the role of the AP in the central L-Arg–NO pathway is not as important as that of the NTS.
We also observed dose-dependent depressor and bradycardic effects and inhibition of RSNA after microinjection of L-Arg into the RVLM. Microinjection of L-NMMA produced slight pressor and tachycardic effects and increased RSNA. These results are similar to the report of Shapoval et al33 in cats. The mechanism of action of these agents also related to guanylate cyclase and cGMP, since methylene blue can inhibit the effects of endothelium-derived relaxing factor–related agents in this area.34 These data further suggest that NO may play a role as a second messenger or neurotransmitter in the important central cardiovascular control nuclei.
In conclusion, our data suggest that NO is involved in central cardiovascular regulation. The depressor effect of L-Arg in the NTS and RVLM and pressor effect of L-NMMA in the NTS and RVLM might be through the inhibition or potentiation of RSNA.
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Selected Abbreviations and Acronyms |
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Acknowledgments |
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This work was supported by NSC 84-2331-B016-047 to Dr Ching-Jiunn Tseng.
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Footnotes |
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Reprint requests to Ching-Jiunn Tseng, MD, PhD, Department of Medical Education and Research, Veterans General Hospital–Kaohsiung, 386 Ta-Chung 1st Rd, Kaohsiung, Taiwan, Republic of China.
Portions of this work were presented at the 24th Annual Meeting of Neuroscience, Miami, Fla, November 13-18, 1994.
Received July 11, 1995; first decision September 11, 1995; accepted September 11, 1995.
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 Y. Kimura, Y. Hirooka, Y. Sagara, K. Ito, T. Kishi, H. Shimokawa, A. Takeshita, and K. Sunagawa Overexpression of Inducible Nitric Oxide Synthase in Rostral Ventrolateral Medulla Causes Hypertension and Sympathoexcitation via an Increase in Oxidative Stress Circ. Res., February 4, 2005; 96(2): 252 - 260. [Abstract] [Full Text] [PDF]
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T. J. Scislo, N. Tan, and D. S. O'Leary Differential role of nitric oxide in regional sympathetic responses to stimulation of NTS A2a adenosine receptors Am J Physiol Heart Circ Physiol, February 1, 2005; 288(2): H638 - H649. [Abstract] [Full Text] [PDF]
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 Y. Hamada, Y. Kameyama, H. Narita, K. T. Benson, and H. Goto Protamine After Heparin Produces Hypotension Resulting from Decreased Sympathetic Outflow Secondary to Increased Nitric Oxide in the Central Nervous System Anesth. Analg., January 1, 2005; 100(1): 33 - 37. [Abstract] [Full Text] [PDF]
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H.-N. Huang, P.-J. Lu, W.-C. Lo, C.-H. Lin, M. Hsiao, and C.-J. Tseng In Situ Akt Phosphorylation in the Nucleus Tractus Solitarii Is Involved in Central Control of Blood Pressure and Heart Rate Circulation, October 19, 2004; 110(16): 2476 - 2483. [Abstract] [Full Text] [PDF]
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V. M. Campese, S. Ye, H. Zhong, V. Yanamadala, Z. Ye, and J. Chiu Reactive oxygen species stimulate central and peripheral sympathetic nervous system activity Am J Physiol Heart Circ Physiol, August 1, 2004; 287(2): H695 - H703. [Abstract] [Full Text] [PDF]
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D. A. Chianca Jr., L.-H. Lin, D. N. Dragon, and W. T. Talman NMDA receptors in nucleus tractus solitarii are linked to soluble guanylate cyclase Am J Physiol Heart Circ Physiol, April 1, 2004; 286(4): H1521 - H1527. [Abstract] [Full Text] [PDF]
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D. F. McKeogh, T. L. O'Donaughy, and V. L. Brooks NO and endogenous angiotensin II interact in the generation of renal sympathetic nerve activity in conscious rats Am J Physiol Heart Circ Physiol, April 1, 2004; 286(4): H1258 - H1265. [Abstract] [Full Text] [PDF]
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C.-H. Lin, W.-C. Lo, M. Hsiao, C.-S. Tung, and C.-J. Tseng Interactions of Carbon Monoxide and Metabotropic Glutamate Receptor Groups in the Nucleus Tractus Solitarii of Rats J. Pharmacol. Exp. Ther., March 1, 2004; 308(3): 1213 - 1218. [Abstract] [Full Text] [PDF]
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 S. H. H. Chan, K.-F. Chang, C.-C. Ou, and J. Y. H. Chan Nitric Oxide Regulates c-fos Expression in Nucleus Tractus Solitarii Induced by Baroreceptor Activation via cGMP-Dependent Protein Kinase and cAMP Response Element-Binding Protein Phosphorylation Mol. Pharmacol., February 1, 2004; 65(2): 319 - 325. [Abstract] [Full Text] [PDF]
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J. Cui, R. Zhang, T. E. Wilson, S. Witkowski, C. G. Crandall, and B. D. Levine Nitric oxide synthase inhibition does not affect regulation of muscle sympathetic nerve activity during head-up tilt Am J Physiol Heart Circ Physiol, November 1, 2003; 285(5): H2105 - H2110. [Abstract] [Full Text] [PDF]
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Y. Wang, K. P. Patel, K. G. Cornish, K. M. Channon, and I. H. Zucker nNOS gene transfer to RVLM improves baroreflex function in rats with chronic heart failure Am J Physiol Heart Circ Physiol, October 1, 2003; 285(4): H1660 - H1667. [Abstract] [Full Text] [PDF]
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C.-H. Lin, W.-C. Lo, M. Hsiao, and C.-J. Tseng Interaction of Carbon Monoxide and Adenosine in the Nucleus Tractus Solitarii of Rats Hypertension, September 1, 2003; 42(3): 380 - 385. [Abstract] [Full Text] [PDF]
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 N. Toda and T. Okamura The Pharmacology of Nitric Oxide in the Peripheral Nervous System of Blood Vessels Pharmacol. Rev., June 1, 2003; 55(2): 271 - 324. [Abstract] [Full Text] [PDF]
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T. Kishi, Y. Hirooka, Y. Kimura, K. Sakai, K. Ito, H. Shimokawa, and A. Takeshita Overexpression of eNOS in RVLM Improves Impaired Baroreflex Control of Heart Rate in SHRSP Hypertension, February 1, 2003; 41(2): 255 - 260. [Abstract] [Full Text] [PDF]
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A. C. R. Dias, E. Colombari, and S. W. Mifflin Effect of nitric oxide on excitatory amino acid-evoked discharge of neurons in NTS Am J Physiol Heart Circ Physiol, January 1, 2003; 284(1): H234 - H240. [Abstract] [Full Text] [PDF]
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E. A. Bocchi, G. Guimaraes, A. Mocelin, F. Bacal, G. Bellotti, and J. F. Ramires Sildenafil Effects on Exercise, Neurohormonal Activation, and Erectile Dysfunction in Congestive Heart Failure: A Double-Blind, Placebo-Controlled, Randomized Study Followed by a Prospective Treatment for Erectile Dysfunction Circulation, August 27, 2002; 106(9): 1097 - 1103. [Abstract] [Full Text] [PDF]
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S. Ye, H. Zhong, V. N. Duong, and V. M. Campese Losartan Reduces Central and Peripheral Sympathetic Nerve Activity in a Rat Model of Neurogenic Hypertension Hypertension, June 1, 2002; 39(6): 1101 - 1106. [Abstract] [Full Text] [PDF]
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V. M. Campese, S. Ye, and H. Zhong Downregulation of Neuronal Nitric Oxide Synthase and Interleukin-1{beta} Mediates Angiotensin II-Dependent Stimulation of Sympathetic Nerve Activity Hypertension, February 1, 2002; 39(2): 519 - 524. [Abstract] [Full Text] [PDF]
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Y.-F. Li, W. G. Mayhan, and K. P. Patel NMDA-mediated increase in renal sympathetic nerve discharge within the PVN: role of nitric oxide Am J Physiol Heart Circ Physiol, December 1, 2001; 281(6): H2328 - H2336. [Abstract] [Full Text] [PDF]
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S. C. Tjen-A-Looi, N. T. Phan, and J. C. Longhurst Nitric oxide modulates sympathoexcitatory cardiac-cardiovascular reflexes elicited by bradykinin Am J Physiol Heart Circ Physiol, November 1, 2001; 281(5): H2010 - H2017. [Abstract] [Full Text] [PDF]
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J. Y.H. Chan, L.-L. Wang, K. L.H. Wu, and S. H.H. Chan Reduced Functional Expression and Molecular Synthesis of Inducible Nitric Oxide Synthase in Rostral Ventrolateral Medulla of Spontaneously Hypertensive Rats Circulation, October 2, 2001; 104(14): 1676 - 1681. [Abstract] [Full Text] [PDF]
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T. Kishi, Y. Hirooka, K. Sakai, H. Shigematsu, H. Shimokawa, and A. Takeshita Overexpression of eNOS in the RVLM Causes Hypotension and Bradycardia Via GABA Release Hypertension, October 1, 2001; 38(4): 896 - 901. [Abstract] [Full Text] [PDF]
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I. Matsuo, Y. Hirooka, K. Hironaga, K. Eshima, H. Shigematsu, M. Shihara, K. Sakai, and A. Takeshita Glutamate release via NO production evoked by NMDA in the NTS enhances hypotension and bradycardia in vivo Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2001; 280(5): R1285 - R1291. [Abstract] [Full Text] [PDF]
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J. Li and J. T. Potts NO formation in nucleus tractus solitarii attenuates pressor response evoked by skeletal muscle afferents Am J Physiol Heart Circ Physiol, May 1, 2001; 280(5): H2371 - H2379. [Abstract] [Full Text] [PDF]
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 J. F R Paton, J. Deuchars, Z. Ahmad, L-F Wong, D. Murphy, and S. Kasparov Adenoviral vector demonstrates that angiotensin II-induced depression of the cardiac baroreflex is mediated by endothelial nitric oxide synthase in the nucleus tractus solitarii of the rat J. Physiol., March 1, 2001; 531(2): 445 - 458. [Abstract] [Full Text] [PDF]
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H. C. D. Souza, G. Ballejo, M. C. O. Salgado, V. J. Dias Da Silva, and H. C. Salgado Cardiac sympathetic overactivity and decreased baroreflex sensitivity in L-NAME hypertensive rats Am J Physiol Heart Circ Physiol, February 1, 2001; 280(2): H844 - H850. [Abstract] [Full Text] [PDF]
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G. Y. Sy, V. Bruban, P. Bousquet, and J. Feldman Nitric Oxide and Central Antihypertensive Drugs : One More Difference Between Catecholamines and Imidazolines Hypertension, February 1, 2001; 37(2): 246 - 249. [Abstract] [Full Text] [PDF]
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S. Ye, P. Mozayeni, M. Gamburd, H. Zhong, and V. M. Campese Interleukin-1beta and neurogenic control of blood pressure in normal rats and rats with chronic renal failure Am J Physiol Heart Circ Physiol, December 1, 2000; 279(6): H2786 - H2796. [Abstract] [Full Text] [PDF]
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K. Sakai, Y. Hirooka, I. Matsuo, K. Eshima, H. Shigematsu, H. Shimokawa, and A. Takeshita Overexpression of eNOS in NTS Causes Hypotension and Bradycardia In Vivo Hypertension, December 1, 2000; 36(6): 1023 - 1028. [Abstract] [Full Text] [PDF]
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 V. M Campese, Shaohua Ye, R. H Truong, and M. Gamburd Losartan reduces sympathetic nerve outflow from the brain of rats with chronic renal failure Journal of Renin-Angiotensin-Aldosterone System, June 1, 2000; 1(2): 202 - 208. [Abstract] [PDF]
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W.-C. Lo, C.-R. Jan, H.-T. Chiang, and C.-J. Tseng Modulatory Effects of Carbon Monoxide on Baroreflex Activation in Nucleus Tractus Solitarii of Rats Hypertension, June 1, 2000; 35(6): 1253 - 1257. [Abstract] [Full Text] [PDF]
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H.-C. Lin, F.-J. Wan, B.-H. Kang, C.-C. Wu, and C.-J. Tseng Systemic Administration of Lipopolysaccharide Induces Release of Nitric Oxide and Glutamate and c-fos Expression in the Nucleus Tractus Solitarii of Rats Hypertension, May 1, 1999; 33(5): 1218 - 1224. [Abstract] [Full Text] [PDF]
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J.-L. Liu and I. H. Zucker Regulation of Sympathetic Nerve Activity in Heart Failure : A Role for Nitric Oxide and Angiotensin II Circ. Res., March 5, 1999; 84(4): 417 - 423. [Abstract] [Full Text] [PDF]
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C. Baylis, J. Harvey, B. R. Santmyire, and K. Engels Pressor and Renal Vasoconstrictor Responses to Acute Systemic Nitric Oxide Synthesis Inhibition Are Independent of the Sympathetic Nervous System and Angiotensin II J. Pharmacol. Exp. Ther., February 1, 1999; 288(2): 693 - 698. [Abstract] [Full Text]
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R. Ma, I. H. Zucker, and W. Wang Reduced NO enhances the central gain of cardiac sympathetic afferent reflex in dogs with heart failure Am J Physiol Heart Circ Physiol, January 1, 1999; 276(1): H19 - H26. [Abstract] [Full Text] [PDF]
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R. Zatz and C. Baylis Chronic Nitric Oxide Inhibition Model Six Years On Hypertension, December 1, 1998; 32(6): 958 - 964. [Full Text] [PDF]
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W.-C. Lo, C.-R. Jan, S.-N. Wu, and C.-J. Tseng Cardiovascular Effects of Nitric Oxide and Adenosine in the Nucleus Tractus Solitarii of Rats Hypertension, December 1, 1998; 32(6): 1034 - 1038. [Abstract] [Full Text] [PDF]
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K. Zhang and K. P. Patel Effect of nitric oxide within the paraventricular nucleus on renal sympathetic nerve discharge: role of GABA Am J Physiol Regulatory Integrative Comp Physiol, September 1, 1998; 275(3): R728 - R734. [Abstract] [Full Text] [PDF]
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A. Sakima, H. Teruya, M. Yamazato, R. Matayoshi, H. Muratani, and K. Fukiyama Prolonged NOS inhibition in the brain elevates blood pressure in normotensive rats Am J Physiol Regulatory Integrative Comp Physiol, August 1, 1998; 275(2): R410 - R417. [Abstract] [Full Text] [PDF]
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K. Matsumura, I. Abe, T. Tsuchihashi, and M. Fujishima Central nitric oxide attenuates the baroreceptor reflex in conscious rabbits Am J Physiol Regulatory Integrative Comp Physiol, April 1, 1998; 274(4): R1142 - R1149. [Abstract] [Full Text] [PDF]
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S. Kagiyama, T. Tsuchihashi, I. Abe, and M. Fujishima Enhanced Depressor Response to Nitric Oxide in the Rostral Ventrolateral Medulla of Spontaneously Hypertensive Rats Hypertension, April 1, 1998; 31(4): 1030 - 1034. [Abstract] [Full Text] [PDF]
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H. Murakami, J.-L. Liu, H. Yoneyama, Y. Nishida, K. Okada, H. Kosaka, H. Morita, and I. H. Zucker Blockade of neuronal nitric oxide synthase alters the baroreflex control of heart rate in the rabbit Am J Physiol Regulatory Integrative Comp Physiol, January 1, 1998; 274(1): R181 - R186. [Abstract] [Full Text] [PDF]
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K. Hironaga, Y. Hirooka, I. Matsuo, M. Shihara, T. Tagawa, Y. Harasawa, and A. Takeshita Role of Endogenous Nitric Oxide in the Brain Stem on the Rapid AdaptatKion of Baroreflex Hypertension, January 1, 1998; 31(1): 27 - 31. [Abstract] [Full Text]
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H. R. Morris, A. T. Etienne, M. Panico, J. R. Tippins, J. Alaghband-Zadeh, S. M. Holland, S. Mehdizadeh, S. Jackie de Belleroche, I. Das, N. S. Khan, et al. Hypothalamic Hypertensive Factor : An Inhibitor of Nitric Oxide Synthase Activity Hypertension, December 1, 1997; 30(6): 1493 - 1498. [Abstract] [Full Text]
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W.-C. Lo, H.-C. Lin, L.-P. Ger, C.-S. Tung, and C.-J. Tseng Cardiovascular Effects of Nitric Oxide and N-Methyl-D-Aspartate Receptors in the Nucleus Tractus Solitarii of Rats Hypertension, December 1, 1997; 30(6): 1499 - 1503. [Abstract] [Full Text]
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R. A. Johnson, E. Colombari, D. S. A. Colombari, M. Lavesa, W. T. Talman, and A. Nasjletti Role of Endogenous Carbon Monoxide in Central Regulation of Arterial Pressure Hypertension, October 1, 1997; 30(4): 962 - 967. [Abstract] [Full Text]
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M. C. Martins-Pinge, I. Baraldi-Passy, and O. U. Lopes Excitatory Effects of Nitric Oxide Within the Rostral Ventrolateral Medulla of Freely Moving Rats Hypertension, September 1, 1997; 30(3): 704 - 707. [Abstract] [Full Text]
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M. M. Gironacci, P. S. Lorenzo, and E. Adler-Graschinsky Possible Participation of Nitric Oxide in the Increase of Norepinephrine Release Caused by Angiotensin Peptides in Rat Atria Hypertension, June 1, 1997; 29(6): 1344 - 1350. [Abstract] [Full Text]
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