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Am J Physiol Heart Circ Physiol 290: H1059-H1063, 2006. First published October 14, 2005; doi:10.1152/ajpheart.00219.2005
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Role of nitric oxide and prostanoids in attenuation of rapid baroreceptor resetting

Maria Cristina O. Salgado,1 Soraia V. S. Justo,2 Luis F. Joaquim,2 Rubens Fazan, Jr.,2 and Helio C. Salgado2

Departments of 1Pharmacology and 2Physiology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil

Submitted 7 March 2005 ; accepted in final form 10 October 2005


   ABSTRACT
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 ABSTRACT
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
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Because the regulation of vascular function involves complex mutual interactions between nitric oxide (NO) synthase (NOS) and cyclooxygenase (COX) products, we examined the contribution of NO and prostanoids derived from the COX pathway in modulating aortic baroreceptor resetting during an acute (30 min) increase in arterial pressure in anesthetized rats. Increase in pressure was induced either by administration of the nonselective NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME) or aortic coarctation (COA) with or without treatment with the COX inhibitor indomethacin (INDO) or the selective neuronal NOS inhibitor 1-(2-trifluoromethylphenyl)imidazole (TRIM). The activity of the aortic depressor nerve and arterial pressure were simultaneously recorded, and the degree of resetting was determined by the shift of the pressure-nerve activity curve using the ratio [{Delta} systolic pressure at 50% of maximum baroreceptor activity/{Delta} systolic pressure] x 100. The magnitude of pressure rise was similar in the different groups (59 ± 6, 53 ± 5, 53 ± 5, 45 ± 5, 49 ± 3, and 41 ± 3 mmHg for COA, L-NAME, INDO+COA, INDO+L-NAME, TRIM+COA, and TRIM+INDO+COA, respectively, P = 0.27). The degree of resetting that occurred with L-NAME or COA combined with treatment with TRIM was attenuated compared with COA alone (7 ± 4, 5 ± 2, and 31 ± 6%, respectively, P = 0.04). INDO failed to influence baroreceptor resetting to higher pressure but prevented L-NAME- and TRIM-induced effects (20 ± 7, 21 ± 8, and 32 ± 6% for INDO+COA, INDO+L-NAME, and INDO+TRIM+COA, respectively; P = 0.38). Baroreceptor gain was affected only by L-NAME. These findings indicate that NO, probably from neuronal origin, may exert stimulatory influence on the degree of rapid baroreceptor resetting to hypertension that involves COX-derived prostanoids.

NG-nitro-L-arginine methyl ester; 1-(2-trifluoromethylphenyl)imidazole; indomethacin; baroreceptor activity

AORTIC BARORECEPTORS are mechanoreceptors stimulated by the stretch of the vessel wall leading to reflex regulation of the cardiovascular system. Therefore, baroreceptor activity promptly buffers arterial pressure fluctuations. Nevertheless, when a change in arterial pressure is maintained, the baroreceptors quickly reset to the new hypotensive or hypertensive level (5, 13).

Although arterial pressure is the main determinant of baroreceptor activity and the resetting of arterial pressure to new levels, baroreceptor sensitivity to changes in pressure can be modulated by autacoids (3, 4). The stretching of a vessel wall not only activates the baroreceptors but also alters the release of endothelial factors, such as nitric oxide (NO) and cyclooxygenase (COX)-derived prostanoids, mostly prostacyclin (PGI2) (20), which may affect baroreceptor activity and/or sensitivity to detect changes in arterial pressure (6).

In isolated carotid sinus from anesthetized rabbits, COX inhibitors attenuated and PGI2 enhanced baroreceptor sensitivity to increases in arterial pressure without altering the pressure-diameter relation, suggesting a role for prostanoids in modulating baroreceptor function (7). On the other hand, NO may modulate baroreceptor function by decreasing the tension imposed on baroreceptor nerve endings by means of vasodilatation and also by exerting a direct effect on baroreceptor nerve terminals. Indeed, endothelial and neuronal NO synthase (NOS)-derived NO could be involved in the modulation of baroreceptor resetting and sensitivity (11, 15). In isolated rabbit carotid sinus preparations, NO or NO donors elicited inhibition of baroreceptor activity that was not related to NO-induced vasodilatation (17). In contrast, carotid sinus baroreceptor function in cats was insensitive to changes in the supply of endogenous or exogenous NO (30).

Most of the experimental evidence demonstrating an influence of NOS or COX products on baroreceptor activity have been generated by studies in isolated carotid sinus preparations, and the potential contribution of NO and prostanoids has been examined separately. In addition, it has become increasingly evident that complex mutual interactions may exist between NOS and COX products. For example, high levels of NO may inhibit or augment the release of PGI2 in endothelial cells (9, 26), and chronic NO inhibition results in the activation of COX (2, 8). Therefore, the aim of the present study was to investigate in vivo a possible role of NO and prostanoids in modulating aortic baroreceptor resetting during sustained increase of arterial pressure. To achieve this purpose, we examined the effect of the nonselective NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME), the selective neuronal NOS inhibitor 1-(2-trifluoromethylphenyl)imidazole (TRIM) (10), and the COX inhibitor indomethacin on baroreceptor activity. In contrast to L-NAME, TRIM and indomethacin do not change arterial pressure by themselves; therefore, to examine the potential contribution of neuronal NOS- or COX-derived products on baroreceptor resetting, the increase in arterial pressure was induced by controlled aortic coarctation.


   MATERIALS AND METHODS
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RESULTS
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Animals. Normotensive male Wistar rats, weighing 250 to 300 g, were used. Animals were kept under controlled temperature and humidity and were exposed to a 12-h:12-h dark-light cycle. They were allowed food and water ad libitum. All experimental procedures were in accordance with guiding principles of the American Physiological Society and approved by our Institutional Review Board.

Surgical procedures and cardiovascular and nerve activity recordings. The procedures for recording the whole nerve activity from the aortic depressor nerve (ADN) have been described previously (1, 25). The rats were anesthetized with pentobarbital sodium (40 mg/kg ip), and catheters were inserted into the right carotid artery for measurement of arterial pressure, into the right femoral artery for withdrawal and reinfusion of blood, and into the femoral vein for administration of drugs. A pneumatic cuff was placed around the abdominal aorta immediately below the diaphragm to promote rapid and sustained increase of arterial pressure to trigger baroreceptor resetting. The left aortic nerve was identified in the neck, carefully isolated from connective tissue, placed on a bipolar stainless steel pair of electrodes, and carefully insulated with a silicon molding material (President-Coltene). The nerve activity was amplified (1,000–3,000x), band-pass filtered (100 Hz–3 kHz) with the use of a differential high impedance amplifier (model 113, Princeton Applied Research), and monitored on an oscilloscope (model 5113, Tektronics) and a loudspeaker. This activity was sampled (10 kHz) simultaneously with the pulsatile carotid pressure in an IBM personal computer equipped with an analog-to-digital interface (Aqdados, Lynx Technology, São Paulo, Brazil).

Experimental protocol. After basal recordings of arterial pressure and ADN activity were measured, baroreceptor firing range was determined as follows: the arterial pressure was decreased by means of controlled hemorrhage until complete cessation of baroreceptor activity and quickly raised by reinfusion of blood associated with aortic constriction until the maximal ADN activity was achieved. After the determination of a pressure-nerve activity curve under basal condition was completed, a prompt and sustained (30-min period) increase in arterial pressure was carried out by means of either aortic constriction, caused by the pneumatic cuff, or by means of the hypertensive effect of L-NAME administration (70 mg/kg iv). At the end of the 30-min period, another pressure-nerve activity curve was determined under the hypertensive condition.

The role of prostanoids on baroreceptor activity was examined in animals that received indomethacin (5 mg/kg iv) 10 min before aortic constriction or received L-NAME. Likewise, a role for NO derived from neuronal NOS was examined in animals pretreated with TRIM (30 mg/kg iv) 10 min before aortic constriction. Accordingly, arterial pressure and baroreceptor activity were recorded from rats (numbers of rats in parenthesis) that received intravenous administration of L-NAME alone (n = 7), indomethacin plus L-NAME (n = 6), and indomethacin (n = 6), TRIM (n = 6), or indomethacin plus TRIM (n = 6) combined with aortic coarctation. Normotensive rats treated with saline (0.1 ml iv; n = 6) and submitted to aortic constriction to induce hypertension were used as controls. The degree of aortic constriction was adjusted to produce increases in pressure similar to the increases induced by L-NAME. The NOS and COX inhibitors were purchased from Sigma (St. Louis, MO) and dissolved in normal saline.

Data analysis. Raw aortic nerve activity (voltage) was rectified and integrated on a pulse-length basis, providing a beat-by-beat series of mean nerve activity. To compare the whole multifiber ADN activity among different rats, the integrated activity was normalized as a function of the maximal activity achieved during the baroreceptor-firing range assessment as described before in Experimental protocol. Normalized ADN activity was plotted against beat-by-beat values of systolic arterial pressure (SAP) to obtain pressure-nerve activity curves. The curves were fitted by a four-parameters sigmoidal regression based on the Levemberg-Marquadt algorithm (16), and the maximum gain (the maximal first derivative of the curve) and the SAP at 50% of maximal nerve activity (SAP50) values were obtained. To avoid the influence of hysteresis, only values obtained during rise in arterial pressure (reinfusion of blood) were used. The ratio between the shift in SAP50 and SAP due to the hypertensive stimulus was used as an index of the degree of baroreceptor resetting as described elsewhere (27).

Statistical analysis. Values are means ± SE. The values of baroreceptor maximum gain were log-transformed and compared among groups, before and after the hypertensive stimulus, by means of the parametric two-way ANOVA for repeated measures with the post hoc Tukey test for multiple comparisons. The nonparametric Kruskal-Wallis one-way ANOVA followed by Dunnet's test was used to compare the extent of resetting as well as the changes in the conditioning mean arterial pressure ({Delta}MAP) among the groups. Changes were considered statistically significant at P < 0.05.


   RESULTS
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DISCUSSION
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Aortic coarctation or L-NAME administration induced a rapid and sustained increase in MAP of similar magnitude in all groups studied (Fig. 1).


Figure 1
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  		Fig. 1. Mean arterial pressure (MAP) obtained before and during 30-min period of sustained hypertension in the following groups: NG-nitro-L-arginine methyl ester (L-NAME) alone, L-NAME combined with indomethacin (INDO+L-NAME), aortic coarctation alone (COA), COA combined with INDO (INDO+COA), COA combined with 1-(2-trifluoromethylphenyl)imidazole (TRIM+COA), and COA combined with INDO and TRIM (INDO+TRIM+COA).

 
Figure 2 shows the pressure-nerve activity curve before (basal condition) and after 30 min of hypertensive stimulus in a rat submitted to aortic constriction alone. In this example, the line between curves (A) illustrates the rightward shift in SAP50 after the stimulus, e.g., from 123 to 140 mmHg, whereas the line at the bottom (B) shows the displacement of SAP from 124 to 182 mmHg, providing a degree of resetting (DR) of 29.3%. The parameters characterize the pressure-nerve activity curve generated before and after the 30-min period of increase in arterial pressure for each group and are presented in Table 1. All groups, except that treated with L-NAME, showed a parallel rightward shift of the curves, indicating that the baroreceptor gain did not change during the hypertensive stimulus. In the group treated with L-NAME, however, the rightward shift of the pressure-nerve activity curve not only did not occur in a parallel manner but also indicated an increase in baroreceptor sensitivity to detect increases in arterial pressure compared with the control period. In animals pretreated with indomethacin, L-NAME failed to affect baroreceptor gain. Indomethacin alone had no significant effect on baroreceptor gain.


Figure 2
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  		Fig. 2. Pressure-nerve activity curve expressed as percentage of maximal aortic depressor nerve (ADN) activity (ADNA) vs. systolic arterial pressure (SAP) using sigmoidal regression. Curves were obtained before (basal) and 30 min after onset of hypertension elicited by aortic constriction in rats that received saline. Percent ratio of shift in SAP at 50% of maximal ADNA (SAP50; a) and shift in SAP (b) induced by hypertensive stimulus was used as degree of baroreceptor resetting (DR). Line A represents displacement of SAP50, and line B represents displacement of SAP after sustained hypertensive stimulus.

 

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  		Table 1. Parameters SAP and SAP50 of pressure-nerve activity curve and gain

 
Figure 3 shows a typical tracing in which baroreceptor activity was recorded simultaneously with pulsatile carotid pressure. Similar increases in MAP elicited by aortic constriction (194 ± 9 mmHg) or treatment with L-NAME (192 ± 8 mmHg) elicited a smaller DR (greater baroreceptor activity) in L-NAME-treated rats compared with aortic coarctation alone (Fig. 3). The DR calculated by the {Delta}SAP50-to-{Delta}SAP ratio determined by the pressure-nerve activity curve in all groups is presented in Fig. 4. A similar hypertensive stimulus elicited a smaller DR in animals treated with either of the NOS inhibitors (L-NAME or TRIM) compared with aortic coarctation alone. In addition, Fig. 4 also shows that the effect of L-NAME or TRIM was abolished in the presence of indomethacin, although indomethacin alone did not significantly affect the degree of baroreceptor resetting during aortic constriction.


Figure 3
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  		Fig. 3. Typical tracings of pulsatile arterial pressure (PAP) and ADNA under basal condition (left), i.e., immediately before prompt, and sustained increase in arterial pressure elicited by administration of aortic coarctation (top) or L-NAME (bottom) and at onset (right after the hypertensive stimulus; middle) and final 30-min period (right) of sustained increase in arterial pressure.

 

Figure 4
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  		Fig. 4. DR calculated by ratio of shift in SAP50 and SAP elicited by COA, INDO+COA, TRIM+COA, L-NAME, L-NAME+INDO, and INDO+TRIM+COA. *P < 0.05 compared with COA.

 

   DISCUSSION
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 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
GRANTS
 REFERENCES
 
The major finding of the present study is that blockade of NOS with L-NAME (a nonspecific inhibitor of NOS) or TRIM (a specific inhibitor of neuronal NOS) attenuated the rapid resetting of the aortic baroreceptors to a prompt and sustained increase in arterial pressure. The maximum gain, which represents baroreceptor sensitivity, was affected by L-NAME but not by TRIM, suggesting that NO, coming from a source distinct from neuronal NOS pathway, decreases baroreceptor sensitivity. Another novel finding is that either L-NAME or TRIM failed to affect baroreceptor activity in indomethacin-pretreated rats, suggesting that NO contributes to the rapid baroreceptor resetting through a COX-dependent mechanism.

Because baroreceptor resetting to hypertensive levels can be defined as a decrease in baroreceptor activity at a constant pressure, we can postulate that any substance inducing a smaller DR is actually increasing baroreceptor activity. The fact that rats treated with either of the NOS inhibitors (L-NAME or TRIM) exhibited a decrease in the DR strongly suggests that inhibition of baroreceptor activity was indeed dependent on NO production. This interpretation is in line with studies (17, 23, 24) showing that the administration of NO or NO donors to carotid sinus and carotid bodies isolated from rabbits or cats inhibits the activity of baroreceptor and chemoreceptor nerves. The functional role of endogenous NO and its ability to chronically inhibit baroreceptor activity and resetting of the baroreceptor function curve to higher pressures were also demonstrated in rabbits using adenoviral-mediated gene transfer of endothelial NOS to carotid sinus adventitia (19). The fact that in the present study both nonselective (L-NAME) and neuronal NOS (TRIM) inhibitors induced a comparable decrease in the degree of baroreceptor resetting to higher pressure strongly suggests that NO from the neuronal source is the one responsible for this effect. This interpretation is supported by the fact that TRIM administration did not affect blood pressure (10), suggesting an inhibition of neuronal NOS without any influencing of endothelial NOS. In fact, immunoreactivity to neuronal isoform of NOS has been detected in baroreceptor neurons (11, 15), raising the possibility that NO may act as an autocrine regulator of baroreceptor nerve activity. In contrast, only L-NAME affected baroreceptor sensitivity (gain) after a 30-min period of maintained increase in arterial pressure, suggesting that NO from nonneuronal sources, most likely from endothelial NOS, is responsible for this effect. The finding that L-NAME increased baroreceptor sensitivity is in agreement with results obtained from rabbit isolated carotid sinus showing that NO or NO donors diminish baroreceptor gain through a mechanism independent of vascular relaxation (17).

In contrast to the diminished extent of baroreceptor resetting to a prompt and maintained hypertension induced by L-NAME observed in the present study, a greater extent of resetting to hypertensive levels was described when another NOS inhibitor NG-nitro-L-arginine (L-NNA) was used (27). It is worth mentioning that the increase in arterial pressure in that study was induced in a ramp progression by L-NNA, attaining a peak value in an approximate 25-min period, whereas in the present study the increase in pressure induced by L-NAME was faster (2–3 min to reach the plateau) due to the characteristic action of this drug. It is accepted that L-NAME represents a prodrug lacking NOS inhibitory activity unless it is hydrolyzed to L-NNA, and bioactivation of L-NAME is markedly accelerated in tissues, such as blood or vascular endothelium (22). Thus, in view of this discrepancy, it is reasonable to speculate that the type of stimulus can affect the contribution of the factors that modulate baroreceptor activity. It is well documented that in anesthetized dogs, carotid sinus nerve activity increases abruptly and then resets (decreases) during the sustained increase in static pressure, whereas the resetting is attenuated during the increase in the mean level of pulsatile pressure, providing support to the notion that the type of stimulus affects the DR of the baroreceptors (5).

A stretching of the vessel wall stimulates not only the endothelium to release NO but also a number of substances, including prostanoids, which may act as paracrine factors modulating baroreceptor activity. Indeed, PGI2, which is the major prostanoid produced by the vascular endothelium, contributes to the activation of baroreceptors and enhances baroreflex inhibition of lumbar sympathetic nerve activity in rabbits (18), whereas indomethacin reduces acute baroreceptor resetting in dogs (28). An impaired production of prostanoids has been described as contributing to decreased baroreceptor activity in hypertensive rabbits (29). In the present study, however, COX inhibition with indomethacin did not affect baroreceptor sensitivity or resetting to hypertension, suggesting that prostanoids do not play an important role modulating baroreceptor function in vivo. This interpretation is consistent with data obtained from healthy humans showing that baroreflex sensitivity was not impaired by acute COX inhibition (21). This finding is important because of the widespread use of nonsteroidal anti-inflammatory drugs, which are powerful inhibitors of COX. Interestingly, inhibition of COX abolished the effect induced by either NOS inhibitors (L-NAME or TRIM) on the degree of baroreceptor resetting to hypertension. These findings are consistent with the notion that there is an interaction between the NOS- and COX-dependent products in the modulation of baroreceptor activity in vivo. Because indomethacin alone did not affect baroreceptor activity, it is reasonable to think that COX-derived products do not influence NOS activity. On the contrary, one explanation could be that NO exerts a negative feedback on COX-mediated prostanoids synthesis; accordingly, the effect of COX-derived products on baroreceptor activity became evident only after NOS inhibition. It is noteworthy that NO has been shown to inhibit oxidation by COX in enzymatic studies in vitro (12). Another possible explanation is that NOS inhibition could induce a shift in the synthesis or in the effects of COX products (14) in favor of prostanoids that have the ability to increase baroreceptor activity. Nevertheless, when COX and NOS are inhibited, other products from the arachidonic acid metabolism may affect baroreceptor function. Therefore, more complex and indirect interactions involving these metabolites cannot be ruled out.

In conclusion, our study in the rat indicates that NO may contribute to rapid baroreceptor resetting during acute hypertension and affect baroreceptor sensitivity in vivo through a COX-dependent mechanism.


   GRANTS
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 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 GRANTS
REFERENCES
 
This study was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo, Conselho Nacional de Desenvolvimento Científico e Tecnológico, and Programa de Apoio a Núcleos de Excelência.


   ACKNOWLEDGMENTS
 
The authors acknowledge the excellent technical assistance of Mauro de Oliveira and Jaci A. Castania.


   FOOTNOTES
 

Address for reprint requests and other correspondence: H. C. Salgado, Dept. of Physiology, School of Medicine of Ribeirão Preto, Univ. of São Paulo, Av. Bandeirantes, 3900, 14049–900, Ribeirão Preto, São Paulo, Brazil (e-mail: hcsalgad{at}fmrp.usp.br)

The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.


   REFERENCES
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 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 GRANTS
 REFERENCES
 

  1. Abreu GR and Salgado HC. Antihypertensive drugs distinctively modulate the rapid resetting of the baroreceptors. Hypertension 15, Suppl 2: I63–I67, 1990.[ISI][Medline]
  2. Baylis C, Slangen B, Hussain S, and Weaver C. Relationship between basal NO release and cyclooxygenase products in the normal rat kidney. Am J Physiol Regul Integr Comp Physiol 271: R1327–R1334, 1996.[Abstract/Free Full Text]
  3. Chapleau MW. Are arterial pressure and deformation the sole determinants of baroreceptor activity? Importance of humoral and endothelial modulation in normal and disease states. Hypertension 19: 278–280, 1992.[Free Full Text]
  4. Chapleau MW and Abboud FM. Modulation of baroreceptor activity by ionic and paracrine mechanisms: an overview. Braz J Med Biol Res 27: 1001–1015, 1994.[ISI][Medline]
  5. Chapleau MW, Hajduczok G, and Abboud FM. Resetting of the arterial baroreflex: peripheral and central mechanisms. In: Reflex Control of the Circulation, edited by Zucker IH and Gilmore JP. Boca Raton, FL: CRC, 1991, p. 141–166.
  6. Chapleau MW, Li Z, Meyrelles SS, Ma X, and Abboud FM. Mechanisms determining sensitivity of baroreceptor afferents in health and disease. Ann NY Acad Sci 940: 1–19, 2001.[Abstract/Free Full Text]
  7. Chen HI, Chapleau MW, McDowell TS, and Abboud FM. Prostaglandins contribute to activation of baroreceptors in rabbits. Possible paracrine influence of endothelium. Circ Res 67: 1394–1404, 1990.[Abstract/Free Full Text]
  8. Da Cunha V, Rossoni LV, Oliveira PA, Poton S, Pretti SC, Vassalo DV, and Stefanon I. Cyclooxygenase inhibition reduces blood pressure elevation and vascular reactivity dysfunction caused by inhibition of nitric oxide synthase in rats. Clin Exp Hypertens 22: 203–215, 2000.[CrossRef][ISI][Medline]
  9. Doni MG, Whittle BJR, Palmer RMJ, and Moncada S. Actions of nitric oxide on the release of prostacyclin from bovine endothelial cells in culture. Eur J Pharmacol 151: 19–25, 1988.[CrossRef][ISI][Medline]
  10. Handy RL, Harb HL, Wallace P, Gaffen Z, Whitehead KJ, and Moore PK. Inhibition of nitric oxide synthase by 1-(2-trifluoromethylphenyl)-imidazole (TRIM) in vitro: antinociceptive and cardiovascular effects. Br J Pharmacol 119, 423–431, 1996.[ISI][Medline]
  11. Höhler B, Mayer B, and Kummer W. Nitric oxide synthase in the rat carotid body and carotid sinus. Cell Tissue Res 276: 559–564, 1994.[ISI][Medline]
  12. Kanner J, Harel S, and Granit R. Nitric oxide, an inhibitor of lipid oxidation by lipoxygenase, cyclooxygenase and hemoglobin. Lipids 27: 46–49, 1992.[ISI][Medline]
  13. Krieger EM, Salgado HC, and Michelini LC. Resetting of the baroreceptors. Int Rev Physiol 26: 119–146, 1982.[ISI][Medline]
  14. Laemmel E, Bonnardel-Phu E, Hou X, Seror J, and Vicaut E. Interaction between nitric oxide and prostanoids in arterioles of rat cremaster muscle in vivo. Am J Physiol Heart Circ Physiol 285: H1254–H1260, 2003.[Abstract/Free Full Text]
  15. Li Z, Chapleau MW, Bates JN, Bielefeldt K, Lee HC, and Abboud FM. Nitric oxide as an autocrine regulator of sodium currents in baroreceptor neurons. Neuron 20: 1039–1049, 1998.[CrossRef][ISI][Medline]
  16. Marquadt DW. An algorithm for least-squares estimates of non-linear parameters. J Soc Ind Appl Math 11: 431–441, 1967.[CrossRef]
  17. Matsuda T, Bates JN, Lewis SJ, Abboud FM, and Chapleau MW. Modulation of baroreceptor activity by nitric oxide and S-nitrosocysteine. Circ Res 76: 426–433, 1995.[Abstract/Free Full Text]
  18. McDowell TS, Axtelle TS, Chapleau MW, and Abboud FM. Prostaglandins in carotid sinus enhance baroreflex in rabbits. Am J Physiol Regul Integr Comp Physiol 257: R445–R450, 1989.[Abstract/Free Full Text]
  19. Meyrelles SS, Sharma RV, Mao HZ, Abboud FM, and Chapleau MW. Modulation of baroreceptor activity by gene transfer of nitric oxide synthase to carotid sinus adventitia. Am J Physiol Regul Integr Comp Physiol 284: R1190–R1198, 2003.[Abstract/Free Full Text]
  20. Mombuli JV and Vanhoutte PM. Endothelial dysfunction: from physiology to therapy. J Mol Cell Cardiol 31: 61–74, 1999.[CrossRef][ISI][Medline]
  21. Monahan KD and Ray CA. Cyclooxygenase inhibition and baroreflex sensitivity in humans. Am J Physiol Heart Circ Physiol 288: H737–H743, 2005.[Abstract/Free Full Text]
  22. Pfeiffer S, Leopold E, Schmidt K, Brunner F, and Mayer B. Inhibition of nitric oxide synthesis by NG-nitro-L-arginine methyl ester (L-NAME): requirement for bioactivation to the free acid, NG-nitro-L-arginine. Br J Pharmacol 118: 1433–1440, 1996.[ISI][Medline]
  23. Prabhakar NR, Kumar GK, Chang CH, Agani FH, and Haxhiu MA. Nitric oxide in the sensory function of the carotid body. Brain Res 625: 16–22, 1993.[CrossRef][ISI][Medline]
  24. Salgado HC and Krieger EM. Time course of baroreceptor resetting in short-term hypotension in the rat. Am J Physiol Heart Circ Physiol 234: H552–H556, 1978.[Free Full Text]
  25. Salvemini D, Currie MG, and Mollace V. Nitric oxide-mediated cyclooxygenase activation. A key event in the antiplatelet effects of nitrovasodilators. J Clin Invest 97: 2562–2568, 1996.[ISI][Medline]
  26. Sun SY, Wang W, Zucker IH, and Schultz HD. Enhanced activity of carotid body chemoreceptors in rabbits with heart failure: role of nitric oxide. J Appl Physiol 86: 1273–1282, 1999.[Abstract/Free Full Text]
  27. Vargas da Silva S, Dias da Silva VJ, Ballejo G, Salgado MCO, and Salgado HC. Blockers of the L-arginine-nitric oxide-cyclic GMP pathway facilitate baroreceptor resetting. Hypertension 23, Suppl 1: I60–I63, 1994.[ISI][Medline]
  28. Wang W, Brandle M, and Zucker IH. Indomethacin reduces acute baroreceptor resetting in the dog. J Physiol 469: 139–151, 1993.[Abstract/Free Full Text]
  29. Xie PL, Chapleau MW, McDowell TS, Hajduczok G, and Abboud FM. Mechanism of decreased baroreceptor activity in chronic hypertensive rabbits. Role of endogenous prostanoids. J Clin Invest 86: 625–630, 1990.[ISI][Medline]
  30. Zanzinger J, Czachurski J, and Seller H. Lack of nitric oxide sensitivity of carotid sinus baroreceptors activated by normal blood pressure stimuli in cats. Neurosci Lett 208: 121–124, 1996.[CrossRef][ISI][Medline]



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