Electrolyte Blood Press.  2009 Dec;7(2):58-66. 10.5049/EBP.2009.7.2.58.

Altered Regulation of Renal Sodium Transporters in Salt-Sensitive Hypertensive Rats Induced by Uninephrectomy

• Jung JY
• Lee JW
• Kim S
• Jung ES
• Jang HR
• Han JS
• Joo KW

• KMID: 2052320
• DOI: http://doi.org/10.5049/EBP.2009.7.2.58

Abstract

Uninephrectomy (uNx) in young rats causes salt-sensitive hypertension (SSH). Alterations of sodium handling in residual nephrons may play a role in the pathogenesis. Therefore, we evaluated the adaptive alterations of renal sodium transporters according to salt intake in uNx-SSH rats. uNx or sham operations were performed in male Sprague-Dawley rats, and normal-salt diet was fed for 4 weeks. Four experimental groups were used: sham-operated rats raised on a high-salt diet for 2 weeks (CHH) or on a low-salt diet for 1 week after 1 week's high-salt diet (CHL) and uNx rats fed on the same diet (NHH, NHL) as the sham-operated rats were fed. Expression of major renal sodium transporters were determined by semiquantitative immunoblotting. Systolic blood pressure was increased in NHH and NHL groups, compared with CHH and CHL, respectively. Protein abundances of Na+/K+/2Cl- cotransporter (NKCC2) and Na+/Cl- cotransporter (NCC) in the CHH group were lower than the CHL group. Expression of epithelial sodium channel (ENaC)-gamma increased in the CHH group. In contrast, expressions of NKCC2 and NCC in the NHH group didn't show any significant alterations, compared to the NHL group. Expressions of ENaC-alpha and ENaC-beta in the NHH group were higher than the CHH group. Adaptive alterations of NKCC2 and NCC to changes of salt intake were different in the uNx group, and changes in ENaC-alpha and ENaC-beta were also different. These altered regulations of sodium transporters may be involved in the pathogenesis of SSH in the uNx rat model.

Keyword

salt-sensitive hypertension; nephrectomy; sodium-potassium-chloride symporters; sodium chloride symporters; epithelial sodium channel

MeSH Terms

Animals
Blood Pressure
Diet
Diet, Sodium-Restricted
Epithelial Sodium Channels
Handling (Psychology)
Humans
Hypertension
Immunoblotting
Male
Nephrectomy
Nephrons
Rats
Rats, Sprague-Dawley
Salicylamides
Social Control, Formal
Sodium
Sodium Chloride Symporters
Sodium-Potassium-Chloride Symporters
Epithelial Sodium Channels
Salicylamides
Sodium
Sodium Chloride Symporters
Sodium-Potassium-Chloride Symporters

Figure

• 

  Fig. 1 Experimental scheme. uNx, uninephrectomy; NS, normal salt diet; HS, high salt diet; LS, low salt diet. CHH: Sham-operated rats raised on a high-salt diet for 2 weeks. CHL: Sham-operated rats raised on a low-salt diet for 1 week after 1 week's high-salt diet. NHH, NHL: uninephrectomized rats fed on the same diet with matched sham-operated rats.

• 

  Fig. 2 Change in systolic blood pressure (SBP). After application of sham or uNx, SBP in rats fed on a high salt diet increased progressively. In rats substituted with low salt diet, the elevation of SBP was attenuated. All of the values are expressed as the mean±standard error. See Fig. 1 legend for description of experimental diets and groups.

• 

  Fig. 3 Pressure-natriuresis curves during the experimental period. These curves illustrate the relationship between the systolic blood pressure (SBP) and 24-hour urinary sodium output. The pressure-sodium excretion curves of the uninephrectomized groups had shifted to the right, and the sham groups had a relative shift to the left. All of the values are expressed as the mean±standard error. See Fig. 1 legend for description of experimental diets and groups.

• 

  Fig. 4 Change in fluid intake and urine volume. In the uninephrectomized groups, both fluid intake and urine volume increased for the entire experimental period. Fractional excretion of sodium (FENa) was also increased after high salt diet. All of the values are expressed as the mean±standard error. Bwt, body weight. See Fig. 1 legend for description of experimental diets and groups.

• 

  Fig. 5 Profiles of sodium transporters and protein abundance change in response to dietary NaCl in the sham-operated group. Protein abundances of Na+/K+/2Cl- cotransporter (NKCC2) and Na+/Cl- cotransporter (NCC) in the CHH group significantly decreased compared to those in the CHL group. Expression of epithelial sodium channel (ENaC)-γ increased in CHH. Each panel is immunoblot loaded with samples from 6 control rats in the CHL group and 6 rats in the CHH group. Blots were probed with antibodies to the type 3 Na+/H+ exchanger (NHE3) of the proximal tubule, the bumetanide-sensitive type 2 NKCC2 of the thick ascending limb of Henle's loop, the thiazide-sensitive NCC of the distal convoluted tubule, and each of the 3 subunits of the amiloridesensitive ENaC. Equality of loading was confirmed by densitometry of parallel Coomassie-stained gels. Values are the means and bars indicate standard error. See Fig. 1 legend for description of experimental diets and groups. *P<0.05 vs control. †P<0.01 vs control.

• 

  Fig. 6 Profiles of sodium transporters and protein abundance change in response to dietary NaCl in the uninephrectomized group. Expressions of Na+/K+/2Cl- cotransporter (NKCC2) and Na+/Cl- cotransporter (NCC) in the NHH group did not show any significant alterations compared with those in the NHL group. Each panel is immunoblot loaded with samples from 6 control rats in the NHL group and 6 rats in the NHH group. Values are the means and bars indicating standard error. NHE3, Na+/H+ exchanger type 3; ENaC, epithelial sodium channel. See Fig. 1 legend for description of experimental diets and groups.

• 

  Fig. 7 Profiles of sodium transporter and protein abundance change between the CHH and NHH group. Protein abundances of Na+/K+/2Cl- cotransporter (NKCC2) in the NHH group significantly decreased compared to those in the CHH group. Expression of epithelial sodium channel (ENaC)-α and ENaC-β increased in the NHH group. Each panel is immunoblot loaded with samples from 6 control rats in the CHH group and 6 rats in the NHH group. Values are the means and bars indicating standard error. NHE3, Na+/H+ exchanger type 3; NCC, Na+/Cl- cotransporter. See Fig. 1 legend for description of experimental diets and groups. *P<0.05 vs control. †P<0.01 vs control.

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