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Am J Physiol Regul Integr Comp Physiol 292: R1557-R1562, 2007. First published December 21, 2006; doi:10.1152/ajpregu.00624.2006
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NEUROHUMORAL CONTROL OF CARDIOVASCULAR FUNCTION

Nitric oxide pathway counteracts enhanced contraction to membrane depolarization in aortic rings of rats on high-sodium diet

Magali Cordaillat,1,3 Aurélie Fort,2 Anne Virsolvy,2 Jean-Luc Elghozi,3 Sylvain Richard,2 and Bernard Jover1

1Groupe Rein et Hypertension, Université Montpellier I and 2INSERM U637, Montpellier; and 3INSERM U652, Paris, France

Submitted 1 September 2006 ; accepted in final form 20 December 2006


   ABSTRACT
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 ABSTRACT
METHODS
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 DISCUSSION
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Vascular smooth muscle cell contraction and endothelium-dependent relaxation was evaluated in aortic rings isolated from weaned, 5-mo-old Sprague-Dawley rats fed a normal (NS; 0.8% NaCl) or high (HS; 8% NaCl) sodium diet. Arterial pressure was 140 ± 6 (NS) and 145 ± 6 mmHg (HS). In endothelium-denuded rings, the response to phenylephrine (PE) was not modified by the sodium diet, while that of depolarizing agent KCl and intracellular calcium releasing agent caffeine increased in the HS group. When endothelium was preserved, PE-evoked contraction was reduced in both NS and HS groups, the contraction being yet lower in the HS group. This effect was partially obliterated by addition of NG-nitro-L-arginine methyl ester (L-NAME), independently of the sodium diet. Relaxation to ACh in intact rings and to sodium nitroprusside (SNP) and 8-bromoadenosine 3'5' cyclic guanosine monophosphate (8-BrcGMP) in the absence of endothelium was enhanced in rings isolated from HS rats. In addition, the dose-response curve to 8-BrcGMP was shifted to the right in the presence of iberiotoxin, an inhibitor of large conductance, voltage-dependent, and calcium-sensitive potassium channel (BKCa). However, shift was more marked in rings from HS rats. Present results provide evidence that response of vascular smooth muscle cell to nitric oxide/cGMP-related compounds is increased in HS rings and is associated with a greater activation of the repolarizing BKCa channels. Such changes might counterbalance enhanced contractile response to membrane depolarization and thus participate in maintenance of arterial pressure in the present model of early and long-term HS feeding in rats.

vascular smooth muscle cell; endothelial cell; sodium nitroprusside; iberiotoxin.

EXCESSIVE CONSUMPTION OF SODIUM is reported to induce cardiac, vascular, and renal alterations in normotensive and hypertensive humans and animals (9, 30). In various strains of rat, a high salt (HS) diet is associated with changes in the reactivity of aortic rings. Many studies conducted in salt-loaded models have shown an increased contraction of vascular smooth muscle cells in response to agonists (1, 14). In addition, relaxation evoked by acetylcholine (ACh) or sodium nitroprusside (SNP) was obliterated in aortic rings isolated from adult spontaneously hypertensive and Dalh-sensitive rats fed a 8% NaCl diet for 4–8 wk (12, 14, 16). These results suggest that concomitant increase in vascular smooth muscle cell contraction and impaired endothelium-dependent relaxation both participate in the development of hypertension in the salt-sensitive strains. In contrast, an enhanced influence of nitric oxide (NO) may have a major role in the lack of rise in blood pressure of sodium-resistant rats when fed a HS diet. In the Dahl-resistant strain (16) and more clearly in the Sprague-Dawley rats (18), NG-nitro-L-arginine methyl ester (L-NAME) or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, a guanylate cyclase inhibitor, enhanced phenylephrine (PE) contraction, and to a greater extent in rats fed an HS than a normal salt (NS) diet. Taken together, these results favor an adaptive response of both the endothelium and the vascular smooth muscle cells to chronic HS intake in adult rats of resistant strains.

Among the mechanisms implicated in endothelial and vascular smooth muscle cell adaptation to HS, the NO pathway might play a key role, as suggested by the enhanced expression of endothelial NO synthase (eNOS) in glomeruli and aorta of Sprague-Dawley rats fed 8% NaCl diet for 4–7 days (28, 29). NO induces activation of the guanylate cyclase and production of cyclic guanosine monophosphate (cGMP), which elicits relaxation through various mechanisms. The stable cGMP analog, 8-bromoadenosine 3'5' cGMP (8-BrcGMP) was reported to activate the myosin light chain phosphatase of smooth muscle strips isolated from the rabbit femoral artery (13, 27). In feline aorta strips, the relaxant effect of nitroprusside and 8-BrcGMP partly occurred via calcium uptake by the endoplasmic reticulum and involves sarcoplasmic reticulum calcium-ATPase (SERCA) (15). cGMP relaxes vascular smooth muscle cells also via hyperpolarization, resulting from activation of cGMP-dependent protein kinase (PKG) and the large-conductance voltage-gated, calcium-sensitive potassium channel (BKCa) (2). In addition, the BKCa channel is highly expressed in the vascular smooth muscle cell (26) and appears to be involved in the vasorelaxing response to ACh in rat aortic rings (19).

In a previous study, feeding weanling rats with an 8% NaCl diet for 4 mo was devoid of major effect on arterial pressure, and it was accompanied by a cardiac and carotid artery hypertrophy (7). Facing the salt loading, change in vascular reactivity may be one of the factors involved in the lack of hypertension observed in the latter model. Therefore, the current investigation was designed to assess vascular smooth muscle cell reactivity to agonists as well as to NO/cGMP related compounds during HS intake. Among the targets of cGMP that can participate in the putative greater influence of the NO pathway in HS-fed rats, the contribution of BKCa channel was evaluated acutely using its pharmacological blockade with iberiotoxin.


   METHODS
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Fifty weanling male Sprague-Dawley rats were randomly assigned to two groups of 25 animals and fed NS or HS diet containing 0.8 or 8% NaCl, respectively, as previously described (7). After 18–20 wk i.e., at 5 mo of age, arterial pressure was measured in the carotid artery of the anesthetized animal (pentobarbital sodium, 50 mg/kg body wt ip; Sanofi), and rats were prepared for the aortic reactivity study.

Aortic Rings Preparation

The thoracic aorta was carefully excised and placed in a physiological solution of the following composition (in mM): 122 NaCl, 5 KCl, 1 MgCl2, 0.5 KH2PO4, 0.5 NaH2PO4, 10 HEPES, 1 NaHCO3, 1.8 CaCl2, and 11 glucose; pH was adjusted to 7.4. The aorta was cleaned of superficial fat and connective tissue and rings of ~3 mm in length were mounted between two triangular stainless steel hooks and placed into an organ bath containing 20 ml of the medium described above. The medium was maintained at 37°C and continuously gassed with oxygen. Isometric tension was measured by an isometric force transducer (EMKA Instruments), connected to a computer system, and recorded by IOX 7.0 software. After an equilibration period of 1 h at a resting tension of 2 g, functional integrity of the rings was tested by the response to a single dose of PE and ACh (10–5 and 10–6 M, respectively). At this dose of PE, the contraction level was similar in the two diet groups. At least 6–8 rings from each rat of the two diet groups were isolated and kept intact or mechanically deendothelialized. In six rats per regimen group, one ring was immediately fixed in 4% formaldehyde for the histological study.

All procedures were in accordance with French law and conform to the Guide for the Care and Use of Laboratory Animals published by the National Institutes of Health (publication No. 85-23, revised 1996).

Aortic Rings Reactivity

Contraction study.
VASCULAR SMOOTH MUSCLE CELL RESPONSE. The contractile capacity of vascular smooth muscle cells was evaluated through the dose response to three different agonists of deendothelialized rings. In a first set of rings, the {alpha}-adrenergic pathway was assessed via the contraction evoked by PE (10–10 to 10–5 M). In the second set of rings, the response to calcium channels activation was determined by direct depolarization of the cell membrane with KCl (10–3 to 10–1 M), while mobilization of intracellular calcium store was evaluated using caffeine (10–4 to 10–2 M).


INFLUENCE OF ENDOTHELIUM ON CONTRACTILE RESPONSE. The dose response to PE was also determined in aortic rings with preserved endothelium, as well as in intact rings preincubated (30 min) with the NO synthase inhibitor L-NAME (10–4 M).

Relaxation study.
RINGS WITH A PRESERVED ENDOTHELIUM. The dose response to ACh (10–9 to 10–6 M) was determined in rings precontracted by 10–5 M of PE. Both PE and ACh responses were repeated 30 min after addition of L-NAME (10–4 M) in the bath.


RINGS WITHOUT ENDOTHELIUM. The vascular smooth muscle cell sensitivity to NO pathway was assessed by the dose response to the NO donor SNP (10–10 to 10–6 M) and the cGMP mimetic 8-BrcGMP (10–6 to 10–4 M) in two different sets of endothelium-denuded rings precontracted with 10–5 M PE. In the last set of experiments, the dose response to 8-BrcGMP was determined in the presence of 10–7 M iberiotoxin, a BKCa channel inhibitor, added to the incubation bath.

Histological Study

Rings fixed in 4% formaldehyde solution were embedded in paraffin. Three 6-µm-thick slices per ring were stained with Sirius Red and Fast Green, and the cross-sectional area (CSA; in mm2) of the media was measured on each section using Image J software (National Institutes of Health, Bethesda, MD). The three measurements were averaged to give a single value of CSA per rat.

Drugs and Data Analysis

All compounds were purchased from Sigma. The doses used in the present study are in the range of those reported by others in the evaluation of vascular reactivity (3, 8, 11, 25). The dose of iberiotoxin chosen was reported to reduce the maximal relaxation induced by an NO-producing drug in aortic rings of normotensive Wistar rats (4).

Data are means ± SE of at least 10 measurements for each dose. The response to PE, KCl, and caffeine was expressed as a change in the basal tension (contraction in g). To minimize the impact of variations in the precontraction level to PE due to the presence or not of endothelium, the response to ACh, SNP, and 8-BrcGMP was expressed as the percentage of the contraction to PE achieved for each ring.

The concentration of drug causing EC50 was determined from the concentration response curve for each ring by using the best fit to a logistic sigmoid function and was averaged to give one value per experimental group.

Data were analyzed with one- or two-way analysis of variance when required. Difference between groups was then assessed with the Fisher least significant difference test. P values <0.05 were considered significant.


   RESULTS
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Rats fed the NS or HS diet had similar final body weight (513 ± 10 and 499 ± 8 g body wt, respectively) and mean arterial pressure (140 ± 6 and 145 ± 6 mmHg, respectively). No statistical difference between aortic CSA of the NS and HS groups was observed (CSA value of 0.989 ± 0.058 and 0.897 ± 0.058 mm2, respectively).

Contraction Study

Vascular smooth muscle cell response. The influence of sodium diet on the response of deendothelialized rings to various constrictor agents is depicted in Fig. 1. The maximal isometric tension developed in response to PE was similar in the HS and NS rings (Fig. 1A). A clear and significant increase in the response to each dose of KCl (Fig. 1B) or caffeine (Fig. 1C) was observed in rings from the HS group. Of note, the EC50 for PE, KCl, and caffeine in endothelium-denuded rings was not modified by the sodium diet (Table 1).


Figure 1
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  		Fig. 1. Contraction study. Influence of sodium diet in deendothelialized rings. Dose-response curve to phenylephrine (PE; A), KCl (B), and caffeine (C) on endothelium-denuded aortic rings from normal salt (NS) and high salt (HS) animals. Data are means ± SE of 12 experiments in each group. *P < 0.05 compared with the NS group.

 

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  		Table 1. Influence of sodium diet on the response to different vasoactive agents

 
Influence of endothelium on contractile response. Isometric tension developed in response to PE was greatly reduced in both sodium regimens when the endothelium was preserved (Fig. 2). Although significance was not achieved, the maximal isometric tension was lower, and the EC50 of PE was higher in intact rings isolated from HS than NS rats (Table 1). When intact rings were preincubated with L-NAME, the isometric tension developed in response to the higher doses of PE was restored to that observed in the absence of endothelium in both regimens (Fig. 2).


Figure 2
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  		Fig. 2. Influence of endothelium and NG-nitro-L-arginine methyl ester (L-NAME) on PE contraction in rats on the 2 sodium diets. Dose-response curve to PE was realized in endothelium-denuded (Endo–), intact (Endo+), and L-NAME-treated Endo+ aortic rings isolated from rats on NS (A) and HS (B) diets. Data are means ± SE of 12 experiments in each group. *P < 0.05 and **P < 0.001 compared with the Endo+ group on the similar diet.

 
Relaxation Study

Rings with a preserved endothelium. Intact rings from HS diet rats presented a greater relaxation and sensitivity to ACh characterized by a significantly lower remaining contraction to PE and a smaller EC50. Pretreatment with L-NAME totally abolished the ACh-induced relaxation in the two groups of diet (Fig. 3, Table 1).


Figure 3
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  		Fig. 3. Relaxation to acetylcholine (ACh) and sodium nitroprusside (SNP). Influence of sodium diet. A: relaxation to ACh assessed in intact ring in the presence ({square}, {blacksquare}) or not ({circ}, bullet) of L-NAME. B: response to SNP determined in Endo–aortic ring. Relaxation is presented as the %contraction remaining after the addition of the agents to precontracted (10–7 M PE) rings isolated from rats fed NS and HS diets. Data are means ± SE of 12 experiments in each group. *P < 0.05 and **P < 0.001 compared with the NS group.

 
Rings without endothelium. On deendothelialized rings, relaxation induced by SNP was more marked in the HS than in the NS group, and the EC50 was lowered in rings isolated from HS rats (Fig. 3, Table 1). Similarly, the contraction remaining after addition of 8-BrcGMP and the EC50 were significantly reduced in denuded rings of the HS group (Fig. 4, Table 1). Addition of iberiotoxin to the incubation bath obliterated the relaxation induced by 8-BrcGMP in the HS and the NS group (Fig. 4). However, the rise in EC50 was more marked in the HS group with approximately a threefold increase compared with the EC50 obtained in the NS group (Table 1).


Figure 4
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  		Fig. 4. Relaxation to 8-bromoadenosine 3'5' cyclic guanosine monophosphate (8-BrcGMP): influence of sodium diet and iberiotoxin (Ibx). A: dose-response curve to 8-BrcGMP alone ({circ}, bullet). B: Dose-response curve to 8-BrcGMP in the presence ({triangleup}, {blacktriangleup}) of Ibx on Endo–aortic rings from NS and HS animals. Data are means ± SE of 12 experiments in each group. *P < 0.05 and **P < 0.001 compared with the NS group; {dagger}P < 0.05 compared with the control group.

 

   DISCUSSION
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The main results of the present study are as follows: 1) the vascular reactivity to PE is lower in intact rings of HS rats and the difference vanishes in the absence of endothelium; 2) the vascular smooth muscle cell reactivity to KCl and caffeine is greater in HS rings; and 3) NO-cGMP dependent relaxation is enhanced in HS rings with a greater activation of the repolarizing BKCa channels.

The present study indicates that vascular reactivity to the {alpha}-agonist PE equated with the EC50 was reduced in endothelium-intact rings isolated from rats fed the HS diet. This finding is in agreement with the reduced precontraction induced by 10–7 M of noradrenaline in aortic rings (17) and the lack of difference in PE-evoked contraction of aortic strips from control and salt-loaded rats (10). Various factors may be involved in the decrease responsiveness to PE in HS rings, including change in arterial pressure and vascular hypertrophy. In the current study, HS diet caused no significant increase in blood pressure. This observation confirms our previous report (7) and is in agreement with observations made with similar (22) or a shorter (10) period of HS feeding. In addition, no aortic hypertrophy was detected in the present HS rats, as previously shown on the carotid artery of a 4-mo-old rat on 2% NaCl diet for 6 mo (25). It is therefore suggested that the reduction of PE response observed in intact rings from HS rats is not related to changes in hemodynamics or structure of the aorta.

Interestingly, PE-evoked contraction was largely increased in the two groups of regimen when the endothelium was removed, and the difference between normal and HS groups vanished as reported by Payne et al. (18). In addition, the response of denuded rings to KCl, which induces voltage-activated calcium entry from the extracellular space, and to caffeine, which mobilizes calcium from the sarcoplasmic reticulum, was markedly higher in the HS than in NS group. An increased sensitivity of the vascular smooth muscle cell to vasoconstrictors, such as noradrenaline, was also previously described in rats fed a HS diet (1). It was also reported that vascular reactivity to PE and KCl is greater in endothelin-infused rats, particularly when fed a 8% NaCl diet during 9 days, and this was associated with increases in calcium entry from the extracellular space (23). Altogether, these results are in favor of an enhanced contractile response of the vascular smooth muscle cell, partly through an increase in calcium stores and activity of voltage-activated calcium channels. The reduced response to PE observed in the present intact HS rings is therefore probably related to functional modification of the endothelium rather than alteration of vascular smooth muscle cell reactivity to constrictors.

In the present experiment, blockade of NO generation by L-NAME in intact rings was associated with a marked enhancement of PE contraction to a level comparable to that observed in the absence of endothelium. In addition, ACh-induced relaxation of intact rings precontracted by PE was higher in the HS than the NS group and was totally abolished by L-NAME in both groups. Although other factor(s), including the endothelium-derived hyperpolarizing factor (24), may participate in the endothelial response of HS rings, the NO/cGMP pathway seems to have a pivotal role in the reduced response to PE of intact HS rings. The higher mRNA and protein levels of eNOS in the arterial wall and the greater basal nitrite/nitrate production by aortic strips reported in rats fed an 8% NaCl diet for 7 days (29) or 9 wk (18) is consistent with such a role. At variance with the present observation, unaffected ACh-induced relaxation (10) and lesser response to methacholine (31) was reported in aortic rings of adult rats fed an HS diet for a short period of time (7 and 3 days, respectively). In the latter study, it was suggested that an HS diet impairs endothelium-dependent relaxation via reduced NO levels. Although changes in NO production cannot be excluded, the greater response to ACh of the present HS rings suggests that compensatory mechanisms developed when the HS diet is proposed since weaning and for a longer period (22 wk) of time.

Besides involvement of the endothelium, an enhanced sensitivity of the vascular smooth muscle cell to NO-related compounds may participate in both the lower response to PE and the higher relaxation evoked by ACh in the present HS- intact rings. The greater relaxation induced by SNP and 8-BrcGMP, as well as their lower EC50 in the denuded HS rings, favors a higher sensitivity of the vascular smooth muscle cells of HS rats to NO-related compounds and suggests that events occurring after cGMP formation are involved. In addition to SERCA activation (15) and actin-myosin complex dissociation (13, 27) by cGMP, the enhanced relaxation to 8-BrcGMP observed in the current HS rings may be also related to changes in repolarization through the large-conductance, voltage-dependent, and BKCa. Highly expressed in the vascular smooth muscle cell (26), BKCa is involved in the relaxation to ACh and NO donor (4, 5, 6, 19), and cGMP has a role in its modulation (2, 20, 21). We show in the present study that iberiotoxin induced a shift in the dose-response curve to 8-BrcGMP in the two diets, confirming the participation of BKCa in the vascular smooth muscle cell relaxation to cGMP in aortic rings. However, the shift was larger in the HS than in the NS group, indicating a more important contribution of BKCa in the 8-BrcGMP-induced relaxation of aorta in animals fed the HS diet. Therefore, it is suggested that the increased activity of the BKCa participates in the enhanced response to 8-BrcGMP, and counteracts the hypersensitivity to membrane depolarization in our model.

In conclusion, the concomitant increase in the vascular smooth muscle cell response to membrane depolarization and NO/cGMP-related compounds is consistent with a local adaptation contributing to maintain normal blood pressure in response to an early and long-lasting HS intake. However, an alteration of the endothelium function might therefore favor imbalance between agonists and endothelial relaxing factors, and lead to a deleterious effect on arterial pressure in this model of HS intake.


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M. Cordaillat was supported by a fellowship from the Ministère de l'Education Nationale, de l'Enseignement Supérieur et de la Recherche. A. Fort was supported by a fellowship from the Servier Laboratories.


   FOOTNOTES
 

Address for reprint requests and other correspondence: B. Jover, Groupe Rein et Hypertension, IURC, 641 Av du doyen Gaston Giraud, 34093 Montpellier Cedex 5, France (e-mail: jover{at}montp.inserm.fr)

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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  1. Adegunloye BJ, Sofola OA. Effect of dietary salt loading and high-calcium diet on vascular smooth muscle responses and endothelium function in rats. Clin Exp Pharmacol Physiol 24: 814–818, 1997.[Web of Science][Medline]
  2. Alioua A, Tanaka Y, Wallner M, Hofmann F, Ruth P, Meera P, Toro L. The large conductance, voltage-dependent, and calcium-sensitive K+ channel, Hslo, is a target of cGMP-dependent protein kinase phosphorylation in vivo. J Biol Chem 273: 32950–32956, 1998.[Abstract/Free Full Text]
  3. Barron LA, Giardina JB, Granger JP, Khalil RA. High-salt diet enhances vascular reactivity in pregnant rats with normal and reduced uterine perfusion pressure. Hypertension 38: 730–735, 2001.[Abstract/Free Full Text]
  4. Bonaventura D, Oliveira FS, da Silva RS, Bendhack LM. Decreased vasodilation induced by a new nitric oxide donor in two-kidney, one-clip hypertensive rats is due to impaired K channel activation. Clin Exp Pharmacol Physiol 32: 478–481, 2005.[CrossRef][Web of Science][Medline]
  5. Callera GE, Yogi A, Tostes RC, Rossoni LV, Bendhack LM. Ca2+-activated K+ channels underlying the impaired acetylcholine-induced vasodilation in 2K-1C hypertensive rats. J Pharmacol Exp Ther 309: 1036–1042, 2004.[Abstract/Free Full Text]
  6. Carrier GO, Fuchs LC, Winecoff AP, Giulumian AD, White RE. Nitrovasodilators relax mesenteric microvessels by cGMP-induced stimulation of Ca-activated K channels. Am J Physiol Heart Circ Physiol 273: H76–H84, 1997.[Abstract/Free Full Text]
  7. Cordaillat M, Rugale C, Casellas D, Mimran A, Jover B. Cardiorenal abnormalities associated with high sodium intake: correction by spironolactone in rats. Am J Physiol Regul Integr Comp Physiol 289: R1137–R1143, 2005.[Abstract/Free Full Text]
  8. Dhanakoti SN, Gao Y, Nguyen MQ, Raj JU. Involvement of cGMP-dependent protein kinase in the relaxation of ovine pulmonary arteries to cGMP and cAMP. J Appl Physiol 88: 1637–1642, 2000.[Abstract/Free Full Text]
  9. du Cailar G, Ribstein J, Daures JP, Mimran A. Sodium and left ventricular mass in untreated hypertensive and normotensive subjects. Am J Physiol Heart Circ Physiol 263: H177–H181, 1992.[Abstract/Free Full Text]
  10. Giardina JB, Green GM, Rinewalt AN, Granger JP, Khalil RA. Role of endothelin B receptors in enhancing endothelium-dependent nitric oxide-mediated vascular relaxation during high salt diet. Hypertension 37: 516–523, 2001.[Abstract/Free Full Text]
  11. Kagota S, Tamashiro A, Yamaguchi Y, Sugiura R, Kuno T, Nakamura K, Kunitomo M. Downregulation of vascular soluble guanylate cyclase induced by high salt intake in spontaneously hypertensive rats. Br J Pharmacol 134: 737–744, 2001.[CrossRef][Web of Science][Medline]
  12. Kagota S, Tamashiro A, Yamaguchi Y, Nakamura K, Kunitomo M. High salt intake impairs vascular nitric oxide/cyclic guanosine monophosphate system in spontaneously hypertensive rats. J Pharmacol Exp Ther 302: 344–351, 2002.[Abstract/Free Full Text]
  13. Lee MR, Li L, Kitazawa T. Cyclic GMP causes Ca2+ desensitization in vascular smooth muscle by activating the myosin light chain phosphatase. J Biol Chem 272: 5063–5068, 1997.[Abstract/Free Full Text]
  14. Luscher TF, Raij L, Vanhoutte PM. Endothelium-dependent vascular responses in normotensive and hypertensive Dahl rats. Hypertension 9: 157–163, 1987.[Abstract/Free Full Text]
  15. Mundina-Weilenmann C, Vittone L, Rinaldi G, Said M, de Cingolani GC, Mattiazzi A. Endoplasmic reticulum contribution to the relaxant effect of cGMP- and cAMP-elevating agents in feline aorta. Am J Physiol Heart Circ Physiol 278: H1856–H1865, 2000.[Abstract/Free Full Text]
  16. Nishida Y, Ding J, Zhou MS, Chen QH, Murakami H, Wu XZ, Kosaka H. Role of nitric oxide in vascular hyper-responsiveness to norepinephrine in hypertensive Dahl ratsJ Hypertens 16: 1611–1618, 1998.[CrossRef][Web of Science][Medline]
  17. Obiefunda PC, Sofola OA, Ebeigbe AB. Dietary salt-loading attenuates endothelium-dependent relaxation in response to histamine but not to acetylcholine in rat aortic rings. Exp Physiol 76: 135–138, 1991.[Abstract]
  18. Payne JA, Alexander BT, Khalil RA. Decreased endothelium-dependent NO-cGMP vascular relaxation and hypertension in growth-restricted rats on a high-salt diet. Hypertension 43: 420–427, 2004.[Abstract/Free Full Text]
  19. Satake N, Shibata M, Shibata S. The involvement of KCa, KATP and KV channels in vasorelaxing responses to acetylcholine in rat aortic rings. Gen Pharmacol 28: 453–457, 1997.[Web of Science][Medline]
  20. Sausbier M, Schubert R, Voigt V, Hirneiss C, Pfeifer A, Korth M, Kleppisch T, Ruth P, Hofmann F. Mechanisms of NO/cGMP-dependent vasorelaxation. Circ Res 87: 825–830, 2000.[Abstract/Free Full Text]
  21. Schubert R, Nelson MT. Protein kinases: tuners of the BKCa channel in smooth muscle. Trends Pharmacol Sci 22: 505–512, 2001.[CrossRef][Medline]
  22. Simon G, Jaeckel M, Illyes G. Development of structural vascular changes in salt-fed rats. Am J Hypertens 16: 488–493, 2003.[CrossRef][Web of Science][Medline]
  23. Smith L, Payne JA, Sedeek MH, Granger JP, Khalil RA. Endothelin-induced increases in Ca2+ entry mechanisms of vascular contraction are enhanced during high-salt diet. Hypertension 41: 787–793, 2003.[Abstract/Free Full Text]
  24. Sofola OA, Knill A, Hainsworth R, Drinkhill M. Change in endothelial function in mesenteric arteries of Sprague-Dawley rats fed a high salt diet. J Physiol 543: 255–260, 2002.[Abstract/Free Full Text]
  25. Streefkerk JO, de Groot AA, Pfaffendorf M, van Zwieten PA. Influence of the nature of pre-contraction on the responses to commonly employed vasodilator agents in rat-isolated aortic rings. Fund Clin Pharmacol 16: 485–494, 2002.[CrossRef][Web of Science][Medline]
  26. Toro L, Marijic J, Nishimaru K, Tanaka Y, Song M, Stefani E. Aging, ion channel expression, and vascular function. Vascul Pharmacol 38: 73–80, 2002.[Web of Science][Medline]
  27. Wu X, Somlyo AV, Somlyo AP. Cyclic GMP-dependent stimulation reverses G-protein-coupled inhibition of smooth muscle myosin light chain phosphate. Biochem Biophys Res Commun 220: 658–663, 1996.[CrossRef][Web of Science][Medline]
  28. Ying WZ, Sanders PW. Dietary salt enhances glomerular endothelial nitric oxide synthase through TGF-beta1. Am J Physiol Renal Physiol 275: F18–F24, 1998.[Abstract/Free Full Text]
  29. Ying WZ, Sanders PW. Dietary salt increases endothelial nitric oxide synthase and TGF-beta1 in rat aortic endothelium. Am J Physiol Heart Circ Physiol 277: H1293–H1298, 1999.[Abstract/Free Full Text]
  30. Yu HC, Burrell LM, Black MJ, Wu LL, Dilley RJ, Cooper ME, Johnston CI. Salt induces myocardial and renal fibrosis in normotensive and hypertensive rats. Circulation 98: 2621–2628, 1998.
  31. Zhu J, Mori T, Huang T, Lombard JH. Effect of high-salt diet on NO release and superoxide production in rat aorta. Am J Physiol Heart Circ Physiol 286: H575–H583, 2004.[Abstract/Free Full Text]




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