Thiazide-Sensitive Cotransporter mRNA Expression Is Not Altered in Three Models of Hypertension

Moreno, Gabriela; Bobadilla, Norma A; González-Salazar, Jorge A; Mercado, Adriana; Tapia, Edilia; Hong, Enrique; Herrera-Acosta, Jaime; Gamba, Gerardo

doi:10.1159/000054207

Cited by 7 publications

(4 citation statements)

References 25 publications

(28 reference statements)

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“…In this context, the downregulation of AQPs and sodium transporters in the clipped kidney may be attributed to the ischemic injury. However, the NCC expression was not altered in the clipped kidney, which is in line with a previous study [32] . The NCC protein may be regulated by the delivery of distal solutes and the activity of the renin-angiotensin system [33] .…”

Section: Discussionsupporting

confidence: 93%

Altered Renal Expression of Aquaporin Water Channels and Sodium Transporters in Rats with Two-Kidney, One-Clip Hypertension

Kwon¹,

Bae²,

Kim³

et al. 2009

Kidney Blood Press Res

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Aims: To determine whether the renal regulation of aquaporin (AQP) water channels and sodium transporters are altered in 2-kidney, 1-clip (2K1C) hypertension. Methods: Male Sprague-Dawley rats were used. They were made 2K1C hypertensive for 1 week. The renal expression of AQPs and sodium transporters was determined by semiquantitative immunoblotting and immunohistochemistry. The activity of adenylyl cyclase was measured by stimulated generation of cAMP. Results: Systolic blood pressure was increased in 2K1C rats. Experimental rats revealed impaired urinary concentration in association with increased urine volume. Urinary sodium excretion also increased. The expression of AQP1–3 was decreased in the clipped kidney compared with the control kidney, whereas it was unchanged in the non-clipped kidney. The adenylyl cyclase activity provoked by arginine vasopressin, sodium fluoride or forskolin was blunted in the clipped kidney, but remained unaltered in the contralateral kidney. The expressions of the Na,K-ATPase α1-subunit, type 3 Na⁺/H⁺ exchanger, Na-K-2Cl cotransporter and epithelial sodium channels were decreased in the clipped kidney, while remaining unchanged in the non-clipped kidney. Conclusion: The downregulation of AQPs and major sodium transporters/channels in the clipped kidney may play a role in the urinary concentration defect and impaired sodium reabsorption in 2K1C hypertension.

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Section: Discussionsupporting

confidence: 93%

Altered Renal Expression of Aquaporin Water Channels and Sodium Transporters in Rats with Two-Kidney, One-Clip Hypertension

Kwon¹,

Bae²,

Kim³

et al. 2009

Kidney Blood Press Res

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“…However, the mRNA level of NCC was not changed at 4, 10, and 16 wk of age in SHR (41). In agreement with this, our results also revealed that the protein expression of NCC was not altered and plasma aldosterone levels were not changed in SHR at 6 and 12 wk of age.…”

Section: Discussionsupporting

confidence: 91%

Increased expression of ENaC subunits and increased apical targeting of AQP2 in the kidneys of spontaneously hypertensive rats

Kim¹,

Wang²,

Kwon³

et al. 2005

American Journal of Physiology-Renal Physiology

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In models of genetic hypertension, renal tubular dysfunction could be involved in the increased sodium and water reabsorption. However, the molecular basis for the increased renal sodium and water retention remains largely undefined in spontaneously hypertensive rats (SHR). We hypothesized that dysregulation of renal epithelial sodium channels (ENaC), sodium (co)transporters, or aquaporin-2 (AQP2) could be involved in the pathogenesis of hypertension in SHR. Six-week-old or twelve-week-old SHR and corresponding age-matched Wistar-Kyoto control rats (WKY) were studied. In both SHR groups, systolic blood pressure was markedly increased, whereas urine output, creatinine clearance, and urinary sodium excretion were decreased compared with corresponding WKY. Moreover, urine osmolality and urine-to-plasma osmolality ratio were increased compared with WKY. Semiquantitative immunoblotting demonstrated that the protein abundance of beta- and gamma-subunits of ENaC was increased in the cortex and outer stripe of the outer medulla and inner stripe of the outer medulla (ISOM) in SHR, whereas alpha-ENaC abundance was increased in ISOM. Immunoperoxidase microscopy confirmed the increased labeling of beta-ENaC and gamma-ENaC subunits in the late distal convoluted tubule, connecting tubule, and cortical and outer medullary collecting duct segments. In contrast, subcellular localization of alpha-ENaC, beta-ENaC, and gamma-ENaC was not changed. Expression of sodium/hydrogen exchanger type 3, bumetanide-sensitive Na-K-2Cl cotransporter, and thiazide-sensitive Na-Cl cotransporter was not altered in SHR. AQP2 levels were increased in the ISOM in SHR, and immunoperoxidase microscopy demonstrated an increased apical labeling of AQP2 in the inner medullary collecting duct in SHR. These results suggest that the increased protein abundance of ENaC subunits as well as the increased apical targeting of AQP2 may contribute to renal sodium and water retention observed during the development of hypertension in SHR.

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“…However, Moreno et al (34) have recently demonstrated that NCC transcript levels did not change in three models of experimental hypertension (including SHR). Therefore, to explain the reported increase in thiazide receptor density, other NCC functions must be envisaged such as stability, protein translation rate, and intracellular distribution.…”

Section: Discussionmentioning

confidence: 97%

Altered expression of renal apical plasma membrane Na⁺transporters in the early phase of genetic hypertension

Capasso

Rizzo²,

Evangelista³

et al. 2005

American Journal of Physiology-Renal Physiology

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-The present study explores whether the development of hypertension in the Milan strain of rats (MHS) rats is preceded or paralleled by alterations of mRNA and/or protein levels of the major luminal Na ϩ transporters. MHS rats were studied at 23-25 days after birth; age-matched Milan normotensive (MNS) rats were used as controls. The glomerular filtration rate (GFR), measured by inulin clearance, was higher in MHS than in MNS rats, while the mean blood pressure was not different in the two strains of animals indicating that the MHS rats were still in the prehypertensive state. Type 3 sodium/hydrogen exchanger (NHE3), bumetanide-sensitive sodium-potassium-2 chloride cotransporter (NKCC2), sodium-chloride cotransporter (NCC) and ␣-ENaC mRNA abundances were quantified by competitive PCR. In MHS compared with MNS, mRNA abundance was unchanged for NHE3 in proximal tubules, higher for NKCC2 in medullary thick ascending limbs of Henle's loops (TAL) and lower for NCC in distal convoluted tubules (DCT) and for ␣-ENaC along collecting ducts (CD). Western blot experiments revealed 1) unchanged NHE3; 2) a significant increase in NKCC2 in the outer medulla; 3) a significant decrease in NCC in the renal cortex and of ␣-ENaC in both the renal cortex and outer medulla, whereas ␤-and ␥-ENaC remained unchanged. These data indicate that, in MHS rats, there is a strong upregulation of NKCC2 along the TAL associated with increased GFR, robust inhibition of NCC cotransporter along the DCT and modest downregulation of ␣-ENaC along the CD. The interplay of the various Na ϩ transporters may well explain why, at this age, the rats are still in the prehypertensive state.type 3 sodium/hydrogen exchanger; sodium-potassium-2chloride cotransporter; sodium-chloride cotransporter; epithelial sodium channel; sodium; kidney HYPERTENSION IS A MAJOR RISK factor for heart disease, stroke, and renal failure. Although its pathogenesis is unknown in the majority of patients, it is becoming evident that the kidney may play an important role in both the induction and maintenance of many types of systemic hypertension. Accordingly, hypertension accompanies the kidney when this organ is transplanted from a genetically hypertensive into a normal rat (5). In addition, recent human genetic studies demonstrate that mutations of genes, encoding for proteins expressed in the kidney and involved in tubular ion transport, are associated with modifications of systemic blood pressure. For instance, lossof-function mutations of transport molecules in the thick ascending limb of Henle's loop (TAL) lead to Bartter's syndrome, and a defective thiazide-sensitive sodium-chloride cotransporter (NCC), present in the distal tubule, is the cause of Gitelman's syndrome (40). The modifications of these iontransporting systems are characterized by urinary sodium loss, resulting in orthostatic hypotension. In contrast, gain-of-function mutations of amiloride-sensitive sodium channels in the collecting ducts generate Liddle's syndrome, which is phenotypically characterized by syst...

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Thiazide-Sensitive Cotransporter mRNA Expression Is Not Altered in Three Models of Hypertension

Cited by 7 publications

References 25 publications

Altered Renal Expression of Aquaporin Water Channels and Sodium Transporters in Rats with Two-Kidney, One-Clip Hypertension

Altered Renal Expression of Aquaporin Water Channels and Sodium Transporters in Rats with Two-Kidney, One-Clip Hypertension

Increased expression of ENaC subunits and increased apical targeting of AQP2 in the kidneys of spontaneously hypertensive rats

Altered expression of renal apical plasma membrane Na⁺transporters in the early phase of genetic hypertension

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Thiazide-Sensitive Cotransporter mRNA Expression Is Not Altered in Three Models of Hypertension

Cited by 7 publications

References 25 publications

Altered Renal Expression of Aquaporin Water Channels and Sodium Transporters in Rats with Two-Kidney, One-Clip Hypertension

Altered Renal Expression of Aquaporin Water Channels and Sodium Transporters in Rats with Two-Kidney, One-Clip Hypertension

Increased expression of ENaC subunits and increased apical targeting of AQP2 in the kidneys of spontaneously hypertensive rats

Altered expression of renal apical plasma membrane Na+transporters in the early phase of genetic hypertension

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Altered expression of renal apical plasma membrane Na⁺transporters in the early phase of genetic hypertension