Kidney immune cell infiltration and oxidative stress contribute to prenatally programmed hypertension

Stewart, Tyrus; Jung, F; Manning, Jennifer; Vehaskari, V. Matti

doi:10.1111/j.1523-1755.2005.00674.x

Cited by 105 publications

(93 citation statements)

References 50 publications

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“…In some cases, renal interstitial inflammation has been found to occur before the development of hypertension as has been demonstrated in the SHR (37), suggesting that renal cortical interstitial inflammation per se may lead to hypertension. Interestingly, renal inflammation even in the embryo may determine later development of hypertension, as was demonstrated in a model where female pregnant rats were fed a low-protein diet (44). The previous demonstration that the immunosuppressant mycophenolate mofetil attenuates the severity of hypertension induced by chronic nitric oxide synthesis blockade (11,16) and prevents the development of saltsensitive hypertension that occurs following transient induction of ANG II-dependent hypertension (36) is indicative of an important role of renal inflammation in the development of hypertension.…”

Section: Discussionmentioning

confidence: 97%

Renal vascular and tubulointerstitial inflammation and proliferation in Cyp1a1-Ren2 transgenic rats with inducible ANG II-dependent malignant hypertension

Graciano

Mouton²,

Patterson³

et al. 2007

American Journal of Physiology-Renal Physiology

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Graciano ML, Mouton CR, Patterson ME, Seth DM, Mullins JJ, Mitchell KD. Renal vascular and tubulointerstitial inflammation and proliferation in Cyp1a1-Ren2 transgenic rats with inducible ANG II-dependent malignant hypertension. Am J Physiol Renal Physiol 292: F1858 -F1866, 2007. First published March 6, 2007;doi:10.1152/ajprenal.00469.2006.-Transgenic rats with inducible ANG II-dependent malignant hypertension [TGR(Cyp1a1Ren2)] were generated by inserting the mouse Ren2 renin gene into the genome of the rat. The present study was performed to assess renal morphological changes occurring during the development of ANG IIdependent malignant hypertension in these rats. Male Cyp1a1-Ren2 rats (n ϭ 10) were fed normal rat food containing indole-3-carbinol (I3C; 0.3%) for 10 days to induce malignant hypertension. Rats induced with I3C had higher mean arterial pressures (173 Ϯ 9 vs. 112 Ϯ 11 mmHg, P Ͻ 0.01) than noninduced normotensive rats (n ϭ 9). Glomerular damage was evaluated by determination of the glomerulosclerosis index (GSI) in tissue sections stained with periodic acid-Schiff. Kidneys of hypertensive rats had a higher GSI than normotensive rats (21.3 Ϯ 5.6 vs. 3.5 Ϯ 1.31 units). Quantitative analysis of macrophage ED-1-positive cells and proliferating cell nuclear antigen using immunohistochemistry demonstrated increased macrophage numbers in the renal interstitium (106.4 Ϯ 11.4 vs. 58.7 Ϯ 5.0 cells/mm 2 ) and increased proliferating cell number in cortical tubules (37.8 Ϯ 5.7 vs. 24.2 Ϯ 2.1 cells/mm 2 ), renal cortical vessels (2.2 Ϯ 0.5 vs. 0.13 Ϯ 0.07 cells/vessel), and the cortical interstitium (33.6 Ϯ 5.7 vs. 4.2 Ϯ 1.4 cells/mm 2 ) of hypertensive rat kidneys. These findings demonstrate that the renal pathological changes that occur during the development of malignant hypertension in Cyp1a1-Ren2 rats are characterized by inflammation and cellular proliferation in cortical vessels and tubulointerstitium. kidney; glomerulosclerosis; renal injury; immunohistochemistry; renin-angiotensin system; renal pathology; peptide hormones TRANSGENIC RATS WITH INDUCIBLE activation of extrarenal renin gene expression [TGR(Cyp1a1Ren2)] were generated using a renin transgene under the transcriptional control of the cytochrome P-450 (Cyp1a1) promoter (23). This transgenic rat line was created by inserting a mouse Ren2 renin gene, fused to an 11.5-kb fragment of the Cyp1a1 promoter, into the genome of the Fischer 344 rat (23). Cyp1a1, which catalyzes the oxidation of a wide range of endogenous lipophilic compounds and xenobiotics (7, 10, 43), is not constitutively expressed but is highly inducible on exposure to various aryl hydrocarbons such as indole-3-carbinol (I3C) (7,10,14,21,26,33,43). Induction of Cyp1a1 is mediated by the aryl hydrocarbon receptor, which is a basic helix-loop-helix-transcription factor that binds to specific DNA elements in the Cyp1a1 promoter (7, 13, 43). Rats transgenic for the Cyp1a1-Ren2 construct do not constitutively express the Ren2 renin gene. Rather, the Ren2 gene is expressed, primarily i...

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Section: Discussionmentioning

confidence: 97%

Renal vascular and tubulointerstitial inflammation and proliferation in Cyp1a1-Ren2 transgenic rats with inducible ANG II-dependent malignant hypertension

Graciano

Mouton²,

Patterson³

et al. 2007

American Journal of Physiology-Renal Physiology

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“…Other factors, such as increased oxidative stress, renal inflammation, accelerated senescence, and catch-up growth, all likely contribute to eventual renal disease. [165][166][167] N glom in humans varies widely, suggesting that a significant proportion of the general population, especially in areas where HBWs or LBWs are prevalent, may be at risk for developing hypertension and renal disease. Measurement of N glom in vivo remains difficult.…”

Section: Discussionmentioning

confidence: 99%

The Clinical Importance of Nephron Mass

Luyckx

Brenner²

2010

Journal of the American Society of Nephrology

277

243

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“…Increased vascular responses to angiotensin II via oxidant-dependent pathways have been described in animal models of maternal nutrient restriction and are preventable via antioxidant intervention in utero or early postnatally (28). Proinflammatory molecules are upregulated in the kidney after maternal protein restriction (29). Such enhanced functional setpoints of potentially injurious pathways may be necessary cofactors that interact with a modest reduction in nephron number to generate overt renal disease.…”

Section: The Kidney In Intrauterine Growth Restrictionmentioning

confidence: 99%

Developmental Origins of Renal Disease

Bagby

2009

Clinical Journal of the American Society of Nephrology

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Kidney immune cell infiltration and oxidative stress contribute to prenatally programmed hypertension

Abstract: Renal oxidative stress and infiltrating immune cells may play a pathogenetic role in prenatally programmed hypertension. Nitric oxide bioavailability does not appear impaired.

Cited by 105 publications

References 50 publications

Renal vascular and tubulointerstitial inflammation and proliferation in Cyp1a1-Ren2 transgenic rats with inducible ANG II-dependent malignant hypertension

Renal vascular and tubulointerstitial inflammation and proliferation in Cyp1a1-Ren2 transgenic rats with inducible ANG II-dependent malignant hypertension

The Clinical Importance of Nephron Mass

Developmental Origins of Renal Disease

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