Angiotensin II-induced calcium signaling in the afferent arteriole from rats with two-kidney, one-clip hypertension

Helle, Frank; Vågnes, Øyvind; Iversen, Bjarne M.

doi:10.1152/ajprenal.00279.2005

Cited by 26 publications

(26 citation statements)

References 41 publications

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“…Briefly, 6-week-old rats were randomly selected for either the 2K1C or control group, and hypertension was induced by placing a sliver clip on the left renal artery as described previously [18,19]. The control rats were sham-operated, but not clipped.…”

Section: Methodsmentioning

confidence: 99%

Proteomic Analysis of Minimally Damaged Renal Tubular Tissue from Two-Kidney-One-Clip Hypertensive Rats Demonstrates Extensive Changes Compared to Tissue from Controls

Finne

Marti

Leh

et al. 2016

Nephron

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Background: Tubular atrophy and interstitial fibrosis mark the final stage in most forms of progressive kidney diseases. Little is known regarding changes in the tubular proteome. In this study, we investigated changes in the tubular proteome of normal or minimally damaged tubular tissue in the non-clipped kidney from rats with two-kidney one-clip (2K1C) hypertension. Methods: Formalin-fixed paraffin-embedded kidney sections from four 2K1C rats with hypertensive kidney damage and 6 sham rats were used. Tubulointerstitial tissue without discernable interstitial expansion or pronounced tubular alterations was microdissected and this was assumed to represent an early stage of chronic tubular damage in 2K1C. Samples were analyzed by mass spectrometry and relative protein abundances were compared between 2K1C and sham. Results: A total of 1,160 proteins were identified with at least 2 unique peptides, allowing for relative quantitation between samples. Among these, 151 proteins were more abundant, and 192 proteins were less abundant in 2K1C compared with sham. Transgelin, vimentin and creatine kinase B-type were among the proteins that were most increased in 2K1C. Ingenuity Pathway Analysis showed increased abundance of proteins related to Rho signaling and protein turnover (eIF2 signaling and protein ubiquitination), and decreased abundance of proteins related to fatty acid β-oxidation. Conclusion: Tubular tissue from normal or minimally damaged hypertensive kidney damage demonstrate extensive proteomic changes with upregulation of pathways associated with progressive kidney damage, such as Rho signaling and protein turnover. Thus, proteomics presents itself to be a promising tool for the discovery of early damage markers from not yet morphologically visible tubular damage.

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Section: Methodsmentioning

confidence: 99%

Proteomic Analysis of Minimally Damaged Renal Tubular Tissue from Two-Kidney-One-Clip Hypertensive Rats Demonstrates Extensive Changes Compared to Tissue from Controls

Finne

Marti

Leh

et al. 2016

Nephron

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“…To produce chronic renal ischemia, the 2K1C model was utilized. In the same surgery as above, after DNA transfection, the left renal artery was clipped by placing of a U-shaped silver clip with an internal diameter of 0.30 mm as described before (14,28). The same surgical procedures were performed in sham rats, in which the clips were removed in the surgical procedures.…”

Section: Methodsmentioning

confidence: 99%

Silencing of hypoxia-inducible factor-1α gene attenuates chronic ischemic renal injury in two-kidney, one-clip rats

Wang

Zhu

et al. 2014

American Journal of Physiology-Renal Physiology

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Silencing of hypoxia-inducible factor-1␣ gene attenuates chronic ischemic renal injury in two-kidney, one-clip rats. Am J Physiol Renal Physiol 306: F1236 -F1242, 2014. First published March 12, 2014 doi:10.1152/ajprenal.00673.2013.-Overactivation of hypoxia-inducible factor (HIF)-1␣ is implicated as a pathogenic factor in chronic kidney diseases (CKD). However, controversy exists regarding the roles of HIF-1␣ in CKD. Additionally, although hypoxia and HIF-1␣ activation are observed in various CKD and HIF-1␣ has been shown to stimulate fibrogenic factors, there is no direct evidence whether HIF-1␣ is an injurious or protective factor in chronic renal hypoxic injury. The present study determined whether knocking down the HIF-1␣ gene can attenuate or exaggerate kidney damage using a chronic renal ischemic model. Chronic renal ischemia was induced by unilaterally clamping the left renal artery for 3 wk in Sprague-Dawley rats. HIF-1␣ short hairpin (sh) RNA or control vectors were transfected into the left kidneys. Experimental groups were shamϩcontrol vector, clipϩcontrol vector, and clipϩHIF-1␣ shRNA. Enalapril was used to normalize blood pressure 1 wk after clamping the renal artery. HIF-1␣ protein levels were remarkably increased in clipped kidneys, and this increase was blocked by shRNA. Morphological examination showed that HIF-1␣ shRNA significantly attenuated injury in clipped kidneys: glomerular injury indices were 0.71 Ϯ 0.04, 2.50 Ϯ 0.12, and 1.34 Ϯ 0.11, and the percentage of globally damaged glomeruli was 0.02, 34.3 Ϯ 5.0, and 6.3 Ϯ 1.6 in sham, clip, and clipϩshRNA groups, respectively. The protein levels of collagen and ␣-smooth muscle actin also dramatically increased in clipped kidneys, but this effect was blocked by HIF-1␣ shRNA. In conclusion, long-term overactivation of HIF-1␣ is a pathogenic factor in chronic renal injury associated with ischemia/hypoxia. collagen; ␣-smooth muscle actin; renal fibrosis; chronic kidney diseases REDUCED RENAL TISSUE OXYGEN levels have been demonstrated in a large variety of chronic kidney diseases (CKD) in both human patients and in experimental animal models. Hypoxia in CKD results from a combination of structural and functional changes (12, 36). As a result, hypoxia-inducible factor (HIF)-1␣ has been reported to be consistently upregulated in almost all types of CKD (7, 16, 17, 36 -38). However, it is unclear whether upregulation of HIF-1␣ is beneficial or deleterious in progressive CKD. HIF-1␣ is a transcription factor and has been shown to stimulate collagen accumulation (7,15,43,44) and promote the epithelial-to-mesenchymal transition (EMT) (11,35), an important mechanism involved in the progression of CKD (3,33,57,67). Therefore, although upregulation of HIF-1␣ is protective in acute kidney injury (9, 18, 37, 53), ample evidence indicates that long-term overactivation of HIF-1␣ may be a pathogenic factor in CKD (10,16,21,24,36,45).Previous studies have shown that genetic ablation of renal epithelial HIF-1␣ inhibits the development of renal tubulointerstitia...

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“…Fifty-eight rats were assigned to the 2K1C groups and 35 rats to the sham groups. Clipping of the left renal artery and sham surgery were performed as previously described (5). In short, the renal arteries of rats, weighing 120 -130 g, were clipped (0.20-mm internal diameter) during pentobarbital sodium anesthesia (50 -70 mg/kg).…”

Section: Methodsmentioning

confidence: 99%

“…Ca i 2ϩ concentration was measured as fura 2 fluorescence with a PTI imaging system (5). Since the AA consists of both endothelium and smooth muscle, it also contains two independent cytosolic compartments with separate Ca i 2ϩ transients.…”

Section: Methodsmentioning

confidence: 99%

Angiotensin II-induced contraction is attenuated by nitric oxide in afferent arterioles from the nonclipped kidney in 2K1C

Helle¹,

Hultström²,

Skogstrand³

et al. 2009

American Journal of Physiology-Renal Physiology

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, one-clip (2K1C) is a model of renovascular hypertension where we previously found an exaggerated intracellular calcium (Ca i 2ϩ ) response to ANG II in isolated afferent arterioles (AAs) from the clipped kidney (Helle F, Vagnes OB, Iversen BM. Am J Physiol Renal Physiol 291: F140 -F147, 2006). To test whether nitric oxide (NO) ameliorates the exaggerated ANG II response in 2K1C, we studied ANG II (10 Ϫ7 mol/l)-induced calcium signaling and contractility with or without the NO synthase (NOS) inhibitor N G -nitro-L-arginine methyl ester (L-NAME). In AAs from the nonclipped kidney, L-NAME increased the ANG II-induced Ca i 2ϩ response from 0.28 Ϯ 0.05 to 0.55 Ϯ 0.09 (fura 2, 340 nm/380 nm ratio) and increased contraction from 80 Ϯ 6 to 60 Ϯ 6% of baseline (P Ͻ 0.05). In vessels from sham and clipped kidneys, L-NAME had no effect. In diaminofluorescein-FM diacetateloaded AAs from the nonclipped kidney, ANG II increased NOderived fluorescence to 145 Ϯ 34% of baseline (P Ͻ 0.05 vs. sham), but not in vessels from the sham or clipped kidney. Endothelial NOS (eNOS) mRNA and ser-1177 phosphorylation were unchanged in both kidneys from 2K1C, while eNOS protein was reduced in the clipped kidney compared with sham. Cationic amino acid transferase-1 and 2 mRNAs were increased in 2K1C, indicating increased availability of L-arginine for NO synthesis, but counteracted by decreased scavenging of the eNOS inhibitor asymmetric dimethylarginine by dimethylarginine dimethylaminohydrolase 2. In conclusion, the Ca i 2ϩ and contractile responses to ANG II are blunted by NO release in the nonclipped kidney. This may protect the nonclipped kidney from the hypertension and elevated ANG II levels in 2K1C.two-kidney; one-clip; renovascular hypertension TWO-KIDNEY, ONE-CLIP (2K1C) has been studied as an ANG II-dependent model of renovascular hypertension. Earlier studies have demonstrated elevated circulating levels of ANG II, with high ANG II concentration in the cortical tissue of the clipped and nonclipped kidney (20).Renal blood flow (RBF) and intrarenal vascular resistance are controlled by autocrine and paracrine factors as well as myogenic and tubuloglomerular feedback responses. The afferent arteriole (AA) is the main site for RBF and glomerular filtration rate (GFR) regulation and plays an important role during development of 2K1C hypertension (12). The clipped kidney has reduced RBF and GFR (18), impaired autoregulation, and dilated AAs (14). Although RBF autoregulation is reset to higher perfusion pressures, the nonclipped kidney has well-maintained RBF and GFR (6) despite high levels of circulating and cortical tissue ANG II.Previously, we found that the ANG II dose-response curve in AAs from clipped kidneys did not saturate at high doses (10 Ϫ6 M), while those from sham and nonclipped kidneys did (5). The effect of cyclooxygenase (COX) inhibition, together with mRNA and protein (1) expression for the AT 1a receptor, was similar in the nonclipped and clipped kidneys. This indicated that the changed dose-response relationship was...

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Angiotensin II-induced calcium signaling in the afferent arteriole from rats with two-kidney, one-clip hypertension

Cited by 26 publications

References 41 publications

Proteomic Analysis of Minimally Damaged Renal Tubular Tissue from Two-Kidney-One-Clip Hypertensive Rats Demonstrates Extensive Changes Compared to Tissue from Controls

Proteomic Analysis of Minimally Damaged Renal Tubular Tissue from Two-Kidney-One-Clip Hypertensive Rats Demonstrates Extensive Changes Compared to Tissue from Controls

Silencing of hypoxia-inducible factor-1α gene attenuates chronic ischemic renal injury in two-kidney, one-clip rats

Angiotensin II-induced contraction is attenuated by nitric oxide in afferent arterioles from the nonclipped kidney in 2K1C

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