scholarly journals Asymmetric dimethylarginine in angiotensin II-induced hypertension

2010 ◽  
Vol 298 (3) ◽  
pp. R740-R746 ◽  
Author(s):  
Jennifer M. Sasser ◽  
Natasha C. Moningka ◽  
Mark W. Cunningham ◽  
Byron Croker ◽  
Chris Baylis
Keyword(s):  
Nitric Oxide ◽  
Renal Injury ◽  
Asymmetric Dimethylarginine ◽  
Renal Cortex ◽  
Interstitial Fibrosis ◽  
Glomerular Sclerosis ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Plasma Adma ◽  
Induced Hypertension

Recent studies have shown that asymmetric dimethylarginine (ADMA), a nitric oxide synthase inhibitor, is increased in hypertension and chronic kidney disease. However, little is known about the effects of hypertension per se on ADMA metabolism. The purpose of this study was to test the hypothesis that ANG II-induced hypertension, in the absence of renal injury, is associated with increased oxidative stress and plasma and renal cortex ADMA levels in rats. Male Sprague-Dawley rats were treated with ANG II at 200 ng·kg−1·min−1 sc (by minipump) for 1 or 3 wk or at 400 ng·kg−1·min−1 for 6 wk. Mean arterial pressure was increased after 3 and 6 wk of ANG II; however, renal injury (proteinuria, glomerular sclerosis, and interstitial fibrosis) was only evident after 6 wk of treatment. Plasma thiobarbituric acid reactive substances concentration and renal cortex p22phox protein abundance were increased early (1 and 3 wk), but urinary excretion of isoprostane and H2O2 was only increased after 6 wk of ANG II. An increased in plasma ADMA after 6 wk of ANG II was associated with increased lung protein arginine methyltransferase-1 abundance and decreased renal cortex dimethylarginine dimethylaminohydrolase activity. No changes in renal cortex ADMA were observed. ANG II hypertension in the absence of renal injury is not associated with increased ADMA; however, when the severity and duration of the treatment were increased, plasma ADMA increased. These data suggest that elevated blood pressure alone, for up to 3 wk, in the absence of renal injury does not play an important role in the regulation of ADMA. However, the presence of renal injury and sustained hypertension for 6 wk increases ADMA levels and contributes to nitric oxide deficiency and cardiovascular disease.

Abstract 93: Hypertension and Renal Injury Induced by Nitric Oxide Depletion are Ameliorated by Concomitant Depletion of Hydrogen Sulfide

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Sebastiaan Wesseling ◽  
Joost O Fledderus ◽  
Johanna A Dijk ◽  
Chantal Tilburgs ◽  
Marianne C Verhaar ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nitric Oxide ◽  
Renal Injury ◽  
Renal Damage ◽  
No Synthase ◽  
Tubular Epithelium ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Induced Hypertension ◽  
Synthase Inhibitor

Chronic nitric oxide (NO) depletion induces hypertension and renal damage. Chronic kidney disease is associated with decreased NO availability and less renal H 2 S production. We hypothesized that combined depletion of NO and H 2 S aggravates hypertension and renal injury. Male 8-wk old Sprague Dawley rats were treated with vehicle, NO synthase inhibitor L-NG-nitroarginine (LNNA; 125 mg/L in drinking water), cystathionine-γ-lyase (CSE) inhibitor propargylglycine (PAG; 37.5 mg/kg BW ip daily) or LNNA + PAG for 1 and 4 weeks (6 rats/group). LNNA after 4w increased systolic blood pressure (SBP; 223±10 vs . 137±3 mmHg in controls; P<0.01), proteinuria (144±35 vs. 17±2 mg/d; P<0.01), uremia (16.6±4.2 vs . 7.0±0.4 mmol/L; P<0.05) and tubulo-interstitial injury (P<0.01). LNNA reduced urinary NO metabolite (NOx) excretion by ∼85% after 1w and 4w. PAG alone had no effect on SBP, renal function or injury, but did reduce urinary NOx excretion. Co-treatment with PAG ameliorated LNNA-induced hypertension (182±10 mmHg; P<0.01) and prevented proteinuria (27±3 mg/d), uremia (8.3±0.4 mmol/L) and tubulo-interstitial injury, but did not further reduce urinary NOx excretion. Renal H 2 S production was almost absent in all PAG groups after 1w and 4w (P<0.01) and was reduced in LNNA-treated rats after 4w (4.6±1.4 vs . 9.2±0.5 μmol/hr/mg; P<0.01). Renal HO-1 gene expression was strongly induced in all PAG-treated groups after 1w and 4w (4 to 19-fold; P<0.01) whereas LNNA only increased HO-1 gene expression at 4w (P<0.01). Immunohistochemistry showed that renal HO-1 protein was primarily interstitial in all PAG-treated groups at 1w and 4w. In contrast, LNNA only showed HO-1 in tubular epithelium in conjunction with protein casts. Depleting NO caused hypertension and renal damage followed by reduced renal H 2 S production and increased renal HO-1 expression. Surprisingly, concomitant inhibition of CSE ameliorated hypertension and prevented renal injury. PAG almost completely blocked renal H 2 S production and caused strong induction of renal HO-1, independently of injury, suggesting that H 2 S suppresses renal HO-1 expression. In conclusion, concomitant upregulation of HO-1 expression by inhibition of H 2 S production, prevents LNNA-induced hypertension and renal injury.

scholarly journals Increased activity and expression of Ca2+-dependent NOS in renal cortex of ANG II-infused hypertensive rats

1999 ◽  
Vol 277 (5) ◽  
pp. F797-F804 ◽  
Author(s):  
So Yeon Chin ◽  
Kailash N. Pandey ◽  
Shang-Jin Shi ◽  
Hiroyuki Kobori ◽  
Carol Moreno ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Renal Cortex ◽  
Renal Medulla ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Hypertensive Rats ◽  
Differential Distribution ◽  
Cortical Blood Flow ◽  
Renal Cortical Blood Flow

We have previously demonstrated that nitric oxide (NO) exerts a greater modulatory influence on renal cortical blood flow in ANG II-infused hypertensive rats compared with normotensive rats. In the present study, we determined nitric oxide synthase (NOS) activities and protein levels in the renal cortex and medulla of normotensive and ANG II-infused hypertensive rats. Enzyme activity was determined by measuring the rate of formation ofl-[14C]citrulline froml-[14C]arginine. Western blot analysis was performed to determine the regional expression of endothelial (eNOS), neuronal (nNOS), and inducible (iNOS) isoforms in the renal cortex and medulla of control and ANG II-infused rats. Male Sprague-Dawley rats were prepared by the infusion of ANG II at a rate of 65 ng/min via osmotic minipumps implanted subcutaneously for 13 days and compared with sham-operated rats. Systolic arterial pressures were 127 ± 2 and 182 ± 3 mmHg in control ( n = 13) and ANG II-infused rats ( n = 13), respectively. The Ca2+-dependent NOS activity, expressed as picomoles of citrulline formed per minute per gram wet weight, was higher in the renal cortex of ANG II-infused rats (91 ± 11) than in control rats (42 ± 12). Likewise, both eNOS and nNOS were markedly elevated in the renal cortex of the ANG II-treated rats. In both groups of rats, Ca2+-dependent NOS activity was higher in the renal medulla than in the cortex; however, no differences in medullary NOS activity were observed between the groups. Also, no differences in medullary eNOS levels were observed between the groups; however, medullary nNOS was decreased by 45% in the ANG II-infused rats. For the Ca2+-independent NOS activities, the renal cortex exhibited a greater activity in the control rats (174 ± 23) than in ANG II-infused rats (101 ± 10). Similarly, cortical iNOS was greater by 47% in the control rats than in ANG II-treated rats. No differences in the activity were found for the renal medulla between the groups. There was no detectable signal for iNOS in the renal medulla for both groups. These data indicate that there is a differential distribution of NOS activity, with the Ca2+-dependent activity and protein expression higher in the renal cortex of ANG II-infused rats compared with control rats, and support the hypothesis that increased constitutive NOS activity exerts a protective effect in ANG II-induced hypertension to maintain adequate renal cortical blood flow.

Abstract 514: Jak2 Tyrosine Kinase Mediates Angiotensin II Renal Pathogenesis via its Pressor Dependent Actions

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Peter P Sayeski ◽  
Sung O Park ◽  
Annet Kirabo ◽  
Rebekah Baskin ◽  
Dale M Seth ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Renal Injury ◽  
Interstitial Fibrosis ◽  
Critical Role ◽  
Glomerular Sclerosis ◽  
Control Group ◽  
Mrna Levels ◽  
Ang Ii ◽  
Urine Albumin ◽  
Independent Events

We previously found that Jak2 kinase, expressed within vascular smooth muscle cells (VSMC), plays a critical role in angiotensin II (Ang II)-mediated hypertension. Given that Jak2 mediates both pressor-dependent and pressor-independent events, we sought to determine the role of blood pressure (BP), per se, on the deleterious effects of Jak2 within the kidney. To investigate this, three groups of mice were examined; i) wild type mice (Controls) that received Ang II infusion, ii) mice lacking Jak2 expression within the VSMC (VSMC Jak2 Null) that also received Ang II, and iii) Control mice that received Ang II plus an anti-hypertensive triple therapy (3Rx). After baseline BP recordings, Ang II was infused (1000 ng/kg/min, SC) to all groups and the 3Rx regimen (80 mg/L hydralazine, 5 mg/L reserpine, 30 mg/L hydrochlorothiazide in the drinking water) was initiated two days later to the 3Rx group, in order to maintain BP at similar levels to the VSMC Jak2 Null group. After 28 days of Ang II, mice were euthanized and the kidneys were assessed via histological, molecular, and functional approaches. Chronic Ang II infusion significantly increased the levels of intrarenal Ang II in all three groups; Control = 1,262±283 fmol/g, VSMC Jak2 Null = 1,655±666 fmol/g, and 3Rx = 2,174±588. While Ang II infusion significantly increased the mean BP in the Control group (152 ± 2 mm Hg), it was significantly, and similarly, lower in both the VSMC Jak2 Null and 3Rx groups (125 ± 5 mm Hg and 131 ± 5 mm Hg, respectively). Glomerular sclerosis was absent and interstitial fibrosis ranged from absent- mild- moderate, and was similar in all groups. The increases in i) perivascular infiltration of CD3+ lymphocytes, ii) CTGF gene expression, iii) tubule casts and iv) albuminuria that were observed in the Control mice, were significantly reduced in both the VSMC Jak2 Null and 3Rx groups. [CTGF mRNA Levels: Control = 100%±17, VSMC Jak2 Null = 70%±12*, 3Rx= 56%±17*. Urine Albumin (ng/day): Control = 414 ± 262, VSMC Jak2 Null = 138 ± 172*, 3Rx= 101 ± 89* (*, p<0.05 vs. Control)]. Thus, the early renal injury due to chronic Ang II infusion correlates with increased BP and not with the expression of VSMC-derived Jak2, suggesting that Jak2 contributes to early Ang II-mediated renal injury via its pressor-dependent actions.

scholarly journals Angiotensin II-mediated hypertension impairs nitric oxide-induced NKCC2 inhibition in thick ascending limbs

2016 ◽  
Vol 310 (8) ◽  
pp. F748-F754 ◽  
Author(s):  
Vanesa D. Ramseyer ◽  
Pablo A. Ortiz ◽  
Oscar A. Carretero ◽  
Jeffrey L. Garvin
Keyword(s):  
Nitric Oxide ◽  
Pde5 Inhibitor ◽  
Cell Types ◽  
No Production ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Hypertensive Rats ◽  
No Donor ◽  
Induced Hypertension ◽  
Stimulation Of

In thick ascending limbs (THALs), nitric oxide (NO) decreases NaCl reabsorption via cGMP-mediated inhibition of Na-K-2Cl cotransporter (NKCC2). In angiotensin (ANG II)-induced hypertension, endothelin-1 (ET-1)-induced NO production by THALs is impaired. However, whether this alters NO's natriuretic effects and the mechanisms involved are unknown. In other cell types, ANG II augments phosphodiesterase 5 (PDE5)-mediated cGMP degradation. We hypothesized that NO-mediated inhibition of NKCC2 activity and stimulation of cGMP synthesis are blunted via PDE5 in ANG II-induced hypertension. Sprague-Dawley rats were infused with vehicle or ANG II (200 ng·kg−1·min−1) for 5 days. ET-1 reduced NKCC2 activity by 38 ± 13% ( P < 0.05) in THALs from vehicle-treated rats but not from ANG II-hypertensive rats (Δ: −9 ± 13%). A NO donor yielded similar results as ET-1. In contrast, dibutyryl-cGMP significantly decreased NKCC2 activity in both vehicle-treated and ANG II-hypertensive rats (control: Δ−44 ± 15% vs. ANG II: Δ−41 ± 10%). NO increased cGMP by 2.08 ± 0.36 fmol/μg protein in THALs from vehicle-treated rats but only 1.06 ± 0.25 fmol/μg protein in ANG II-hypertensive rats ( P < 0.04). Vardenafil (25 nM), a PDE5 inhibitor, restored NO's ability to inhibit NKCC2 activity in THALs from ANG II-hypertensive rats (Δ: −60 ± 9%, P < 0.003). Similarly, NO's stimulation of cGMP was also restored by vardenafil (vehicle-treated: 1.89 ± 0.71 vs. ANG II-hypertensive: 2.02 ± 0.32 fmol/μg protein). PDE5 expression did not differ between vehicle-treated and ANG II-hypertensive rats. We conclude that NO-induced inhibition of NKCC2 and increases in cGMP are blunted in ANG II-hypertensive rats due to PDE5 activation. Defects in the response of THALs to NO may enhance NaCl retention in ANG II-induced hypertension.

scholarly journals Serelaxin reduces oxidative stress and asymmetric dimethylarginine in angiotensin II-induced hypertension

2014 ◽  
Vol 307 (12) ◽  
pp. F1355-F1362 ◽  
Author(s):  
Jennifer M. Sasser ◽  
Mark W. Cunningham ◽  
Chris Baylis
Keyword(s):  
Oxidative Stress ◽  
Asymmetric Dimethylarginine ◽  
Oxidation Products ◽  
No Oxidation ◽  
Kidney Cortex ◽  
High Dose ◽  
Protective Effects ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Induced Hypertension

Recent findings suggest the therapeutic action of relaxin during hypertension is dependent on nitric oxide synthase (NOS) activation; however, the mechanisms underlying the beneficial effects of relaxin on the NOS system have not been fully elucidated. We hypothesized that the protective effects of relaxin include reducing both oxidative stress and the endogenous NOS inhibitor asymmetric dimethylarginine (ADMA). We examined the effect of Serelaxin [human recombinant relaxin-2 (RLX)] in male Sprague-Dawley rats given high-dose angiotensin (ANG) II (400 ng·kg−1·min−1 sc) for 6 wk or shams. RLX was administered (4 μg/h sc) to half of the rats in each group after 2 wk of ANG II for the remaining 4 wk. ANG II induced hypertension and proteinuria, reduced NO oxidation products (NOx), and increased oxidative stress (NADPH oxidase activity, thiobarbituric acid-reactive substances, and 8-isoprostane excretion) and plasma ADMA. While RLX had no effect on sham rats, RLX attenuated the ANG II-dependent hypertension (165 ± 5 vs. 135 ± 13 mmHg, P < 0.05) and proteinuria at 6 wk (62 ± 6 vs. 41 ± 4 mg·day−1·100 g−1, P < 0.05) and normalized oxidative stress and circulating ADMA, in association with restored NOx excretion and kidney cortex NOx. We found that RLX had no impact on the ADMA-regulatory enzymes protein arginine methyltransferase and dimethylarginine-dimethylaminohydrolase (DDAH). Furthermore, RLX treatment did not increase DDAH activity in kidney cortex or liver. These data suggest that benefits of RLX treatment include reduced ADMA levels and increased NO bioavailability, possibly due to its antioxidant effects.

scholarly journals Renal injury in angiotensin II+l-NAME-induced hypertensive rats is independent of elevated blood pressure

2011 ◽  
Vol 300 (4) ◽  
pp. F1008-F1016 ◽  
Author(s):  
Aaron J. Polichnowski ◽  
Limin Lu ◽  
Allen W. Cowley
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Renal Injury ◽  
Interstitial Fibrosis ◽  
Left Kidney ◽  
Fold Increase ◽  
Experimental Hypertension ◽  
Human Populations ◽  
Ang Ii ◽  
Sprague Dawley

The balance between angiotensin II (ANG II) and nitric oxide plays an important role in renal function and is thought to contribute to the progression of renal injury in experimental hypertension. In the present study, we investigated the extent of blood pressure (BP)-dependent and BP-independent pathways of renal injury following 2 wk of hypertension produced by intravenous infusion of ANG II (5 ng·kg−1·min−1)+ Nω-nitro-l-arginine methyl ester (l-NAME; 1.4 μg·kg−1·min−1) in male Sprague-Dawley rats. An aortic balloon occluder was positioned between the renal arteries to maintain (24 h/day) BP to the left kidney (servo-controlled) at baseline levels, whereas the right kidney (uncontrolled) was chronically exposed to elevated BP. Over the 14-day experimental protocol, the average BP to uncontrolled kidneys (152.7 ± 1.8 mmHg) was significantly elevated compared with servo-controlled (113.0 ± 0.2 mmHg) kidneys and kidneys from sham rats (108.3 ± 0.1 mmHg). ANG II+l-NAME infusion led to renal injury that was focal in nature and mainly confined to the outer medulla. Despite the differences in BP between servo-controlled and uncontrolled kidneys, there was a similar ∼3.5-fold increase in renal outer medullary tubular injury, ∼2-fold increase in outer medullary interstitial fibrosis, ∼2-fold increase in outer medullary macrophage infiltration, and a significant increase in renal oxidative stress, all of which are indicative of BP-independent mediated pathways. The results of this study have important implications regarding the pathogenesis of renal injury in various experimental models of hypertension and provide novel insights regarding the variable association observed between hypertension and renal injury in some human populations.

Abstract 493: Impact of Renal Vasoconstriction on the Relationship Between Blood Pressure and Renal Injury in Angiotensin II-induced Hypertensive Rats

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Aaron J Polichnowski ◽  
Maria Picken ◽  
Jianrui Long ◽  
Geoffrey Williamson ◽  
Karen Griffin ◽  
...  
Keyword(s):  
Renal Injury ◽  
Left Kidney ◽  
Separate Experiment ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Osmotic Minipump ◽  
Renal Vasoconstriction ◽  
Sprague Dawley Rats ◽  
Induced Hypertension ◽  
The Relationship

Ang II is thought to play a prominent role in the development of hypertension-induced renal disease via BP dependent and independent pathways; however the quantitative relationships between BP and renal injury have not been rigorously examined in Ang II-induced hypertension. The major goals of the present study were to assess: 1) the relationship between BP and renal injury in rats with hypertension induced by Ang II vs. renal mass reduction (RMR) and 2) the pressure-flow relationships in conscious Ang II-infused rats. One group of male Sprague-Dawley rats (Charles River) were implanted with a BP radiotransmitter and 10 days later administered Ang II (n=12; 500 ng/kg/min via osmotic minipump) or subjected to 3/4 RMR via right uninephrectomy + infarction of ∼ 1/2 of the left kidney (RKI, n=5). BP was measured continuously and kidneys were perfused fixed at 6 weeks for the assessment of renal injury. In a separate experiment, MAP and RBF (Transonic) were measured in conscious chronically instrumented rats. After recovery from surgery (∼7 days), baseline MAP and RBF were assessed (∼4 hours @ 200 Hz) on 2 consecutive days. Subsequently, rats were administered Ang II (n=6; 500 ng/kg/min) or saline (n=7; sham) via osmotic minipump and MAP and RBF were again assessed every 2-3 days for 10 days. Despite a higher average systolic BP over 6 weeks in Ang II (174±3 mmHg) vs. RKI (165±6 mmHg) rats, glomerulosclerosis (GS) was higher (p<0.05) in RKI (15±7% out of 100 glomeruli) vs. Ang II (6±1% out of 100 glomeruli) rats. Moreover, the slope of the relationship between BP and %GS (Δ%GS/ΔmmHg) was greater in RKI vs. Ang II rats. Both MAP (98±2 vs. 99±3 mmHg) and RBF (8.1±1vs. 8.2±1 ml/min) were similar at baseline in Ang II and sham rats, respectively. MAP was elevated by day 3 (123±6 mmHg) and further increased to 157±5 mmHg by day 10 in Ang II rats. Conversely, RBF was decreased at day 3 (6.6±0.6 ml/min) and the vasoconstriction persisted over the experimental protocol as RBF further decreased to 5.6±0.7 ml/min at day 10 in Ang II rats. In conclusion, Ang II-induced hypertension is associated with a diminished susceptibility to renal injury as compared to rats with RMR likely due, in part, to the AngII-induced vasoconstriction, which reduces BP transmission to the renal microvasculature.

Gene expression reveals vulnerability to oxidative stress and interstitial fibrosis of renal outer medulla to nonhypertensive elevations of ANG II

2003 ◽  
Vol 284 (5) ◽  
pp. R1219-R1230 ◽  
Author(s):  
Baozhi Yuan ◽  
Mingyu Liang ◽  
Zhizhang Yang ◽  
Elizabeth Rute ◽  
Norman Taylor ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Western Blot ◽  
Renal Injury ◽  
Interstitial Fibrosis ◽  
Control Period ◽  
Renal Medulla ◽  
Differentially Expressed ◽  
Ang Ii ◽  
Outer Medulla ◽  
Renal Outer Medulla

The present study was designed to determine whether nonhypertensive elevations of plasma ANG II would modify the expression of genes involved in renal injury that could influence oxidative stress and extracellular matrix formation in the renal medulla using microarray, Northern, and Western blot techniques. Sprague-Dawley rats were infused intravenously with either ANG II (5 ng · kg−1 · min−1) or vehicle for 7 days ( n = 6/group). Mean arterial pressure averaged 110 ± 0.6 mmHg during the control period and 113 ± 0.4 mmHg after ANG II. The mRNA of 1,751 genes (∼80% of all currently known rat genes) that was differentially expressed (ANG II vs. saline) in renal outer and inner medulla was determined. The results of 12 hybridizations indicated that in response to ANG II, 11 genes were upregulated and 25 were downregulated in the outer medulla, while 11 were upregulated and 13 were downregulated in the inner medulla. These differentially expressed genes, most of which were not known previously to be affected by ANG II in the renal medulla, were found to group into eight physiological pathways known to influence renal injury and kidney function. Particularly, expression of several genes would be expected to increase oxidative stress and interstitial fibrosis in the outer medulla. Western blot analyses confirmed increased expression of transforming growth factor-β1 and collagen type IV proteins in the outer medulla. Results demonstrate that nonhypertensive elevations of plasma ANG II can significantly alter the expression of a variety of genes in the renal outer medulla and suggested the vulnerability of the renal outer medulla to the injurious effect of ANG II.

scholarly journals Improved blood pressure, nitric oxide and asymmetric dimethylarginine are independent after bariatric surgery

2012 ◽  
Vol 49 (6) ◽  
pp. 589-594 ◽  
Author(s):  
R Patle ◽  
S Dubb ◽  
J Alaghband-Zadeh ◽  
R A Sherwood ◽  
F Tam ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Bariatric Surgery ◽  
Weight Loss ◽  
Asymmetric Dimethylarginine ◽  
Obese Patients ◽  
Endogenous Inhibitor ◽  
Nitrite Concentration ◽  
Plasma Adma ◽  
Adma Concentration

Background Obesity is associated with hypertension, but the exact mechanism is not fully understood. Bariatric surgery significantly decreases weight and blood pressure (BP). Low plasma nitric oxide (NO) and raised asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO, concentrations are associated with both obesity and hypertension. Correlations between the changes in these parameters were studied after bariatric surgery. Methods Weight, BP, plasma ADMA and NO were measured in 29 obese patients (24 female, 5 male) before and six weeks after bariatric surgery. Results Patients were 39.2 ± 1.2 (mean ± SEM) years old and weighed 126 ± 3 kg. Six weeks after the surgery, patients had lost 10 ± 0.7 kg ( P < 0.0001) and mean arterial pressure (MAP) decreased by 11 ± 1.0 mmHg ( P < 0.0001). The plasma ADMA concentration decreased by 24 ± 2% from 5 ± 0.4 to 4.0 ± 0.3 μmol/L ( P < 0.0001). The plasma total nitrite concentration increased by 15 ± 1% from 51.4 ± 2.6 to 60 ± 3 μmol/L ( P < 0.0001). The correlation between the decrease of ADMA and increase of NO subsequent to weight loss was significant ( P < 0.0001). However, MAP was not correlated to the changes in ADMA or NO. Conclusions After bariatric surgery, beneficial changes in BP, NO and ADMA occur, but our findings suggest that these BP changes are independent of changes in the NO–ADMA axis. Other causes for the changes in BP should therefore be considered.

The Relevance of Periglomerular Fibrosis in the Evaluation of Routine Needle Core Renal Biopsies

2011 ◽  
Vol 135 (1) ◽  
pp. 117-122
Author(s):  
Joseph Jenkins ◽  
Sergey V. Brodsky ◽  
Anjali A. Satoskar ◽  
Gyongyi Nadasdy ◽  
Tibor Nadasdy
Keyword(s):  
Renal Function ◽  
Renal Biopsy ◽  
Renal Injury ◽  
Interstitial Fibrosis ◽  
Renal Diseases ◽  
Glomerular Sclerosis ◽  
Poor Renal Function ◽  
Renal Biopsies ◽  
Biopsy Report ◽  
Relationship Of

Abstract Context—Renal interstitial fibrosis and, to a lesser extent, sclerotic glomeruli correlate with poor renal function. However, not all nonfunctional glomeruli are sclerotic. Many or most glomeruli with periglomerular fibrosis, while retaining blood flow, probably do not filter; therefore, they may not contribute to renal function. Objective—To examine the relationship of periglomerular fibrosis and the sum of globally sclerotic glomeruli and glomeruli with periglomerular fibrosis (GSG+PF) with interstitial fibrosis and renal function. Design—Native kidney biopsies from 177 patients with chronic renal injury were assessed for interstitial fibrosis, glomerular sclerosis, and GSG+PF. Renal biopsies with active or acute lesions were not included. The percentage of globally sclerotic glomeruli and GSG+PF was correlated with the degree of interstitial fibrosis and serum creatinine levels. Results—The percentage of GSG+PF correlates better with the degree of interstitial fibrosis and renal function than does the percentage of globally sclerotic glomeruli alone. This appears particularly true in chronic renal diseases of patients without diabetes. The number of globally sclerotic glomeruli correlates better with interstitial fibrosis and renal function than does the sum of globally and segmentally sclerotic glomeruli. Conclusions—The percentage of GSG+PF in a renal biopsy specimen provides a better estimate of chronic renal injury than does the percentage of sclerotic glomeruli alone, probably because many or most glomeruli with periglomerular fibrosis are nonfunctional. Therefore, we recommend that the number of glomeruli with periglomerular fibrosis also be provided in the renal biopsy report.

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