Augmentation of diabetes-associated renal hyperfiltration and nitric oxide production by pregnancy in rats

Omer, S.; Shan, Jiehui; Varma, Daya R.; Mulay, Shree

doi:10.1677/joe.0.1610015

Cited by 19 publications

(15 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We (13) previously reported an increase in total NOS activity in renal cortical homogenates in T1D without a corresponding upregulation in any of the three NOS isoforms; however, that study did not evaluate medullary NOS or the subcellular localization of NOS isoforms. Omer et al (24) reported an increase in Ca 2ϩ -dependent NOS activity measured in whole kidney homogenates of female rats studied 2 wk after streptozotocin-induced T1D. Choi et al (4,5) reported unaltered expression of all three NOS isoforms in the renal medulla after 7 and 28 days of streptozotocin-induced T1D, a result similar to the present study.…”

Section: Discussionsupporting

confidence: 89%

Posttranslational regulation of NO synthase activity in the renal medulla of diabetic rats

Lee¹,

Sasser²,

Hobbs³

et al. 2005

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

1177 NOS3 was evident only in the thick ascending limb, with no apparent differences between groups. In summary, glucose-dependent osmotic diuresis alone did not alter NOS activity or expression in the renal medulla. Diabetic hyperglycemia increased medullary NOS3 activity without a concomitant increase in NOS3 protein levels; however, NOS3 phosphorylation was reduced at Thr 495 and Ser 633 . Thus changes in the phosphorylation of NOS at known regulatory sites might represent the primary mechanism underlying increased renal medullary NOS activity in diabetic hyperglycemia. streptozotocin; phosphorylation; phlorizin; nitric oxide synthase; NOS3; NOS1 AN IMPORTANT PHYSIOLOGICAL regulator of renal function, nitric oxide (NO) is synthesized as a by-product of the conversion of L-arginine to L-citrulline. The greatest capacity for renal NO synthesis resides in the medulla (23, 34), which expresses all three isoforms of NO synthase (NOS) (18). A paracrine NO system has been postulated to reside within the renal medulla, relying on cross-talk between epithelial and microvascular cells to match vasa recta blood flow to tubular metabolic transport activity (6). Accordingly, a decrease in NO production achieved by medullary interstitial infusion of NOS inhibitors leads to a reduction in medullary blood flow and salt retention, whereas infusion of NOS substrate increases medullary blood flow (15, 28). A previous report (3) from our laboratory revealed that NO production is modulated by shear stress in an inner medullary collecting duct cell line (IMCD-3), suggesting that tubular fluid flow may play a role in regulating sodium and water excretion by virtue of shear stress-mediated control of NO production. Moreover, Ortiz et al. (27) recently reported that flow stimulates translocation and phosphorylation of NOS3 and an associated increase in NO production by isolated thick ascending limb segments. However, it is unclear whether chronic increases in urine flow per se provoke an increase in NO synthesis and/or NOS expression in the renal medulla. One approach to examining this postulate is to determine whether pathophysiological states associated with increased urine flow are associated with increased NOS activity in the renal medulla. For example, urine flow is significantly increased in type 1 diabetes mellitus (T1D) because of a glucose-dependent osmotic diuresis. Thus, if shear stress represents an important determinant of NO production in the thick ascending limb and/or collecting duct, one would predict that renal medullary NOS activity would be increased in T1D.Most of the literature concerning the renal complications of T1D focuses on alterations in glomerular structure/function or impaired regulation of arteriolar tone/reactivity. However, recent studies have revealed that the early stage of T1D is accompanied by altered expression of multiple renal medullary transport proteins: e.g., the bumetanide-sensitive NaϪ cotransporter; epithelial Na ϩ channel subunits-␣, -␤, and -␥; aquaporins 2 and 3; urea transporter-A1 ...

show abstract

Section: Discussionsupporting

confidence: 89%

Posttranslational regulation of NO synthase activity in the renal medulla of diabetic rats

Lee¹,

Sasser²,

Hobbs³

et al. 2005

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

show abstract

“…Although chronic estrogen exposure upregulates NO, thereby providing vascular protection in females without DM, this interaction may be more complex in the context of DM (26,28–30). …”

Section: Discussionmentioning

confidence: 99%

Sex Differences in Renal Responses to Hyperglycemia, l-Arginine, and l-NMMA in Humans With Uncomplicated Type 1 Diabetes

2013

View full text Add to dashboard Cite

OBJECTIVEWomen exhibit exaggerated renal hemodynamic responses to hyperglycemia, which may promote kidney disease progression. Our aim was to determine if increased nitric oxide generation by l-arginine infusion would reverse this deleterious response to clamped hyperglycemia in women with type 1 diabetes mellitus.RESEARCH DESIGN AND METHODSRenal function, blood pressure, and plasma cyclic guanosine monophosphate (cGMP) were measured in 20 men and 15 women with type 1 diabetes mellitus during clamped euglycemia and clamped hyperglycemia. Renal function, blood pressure, and plasma cGMP responses to graded infusions of intravenous l-arginine and NG-monomethyl-l-arginine (l-NMMA) were measured during clamped hyperglycemia.RESULTSSubjects were young, normotensive, normoalbuminuric men and women who adhered to a high-sodium, moderate-protein diet. Plasma cGMP levels during euglycemia were generally lower in men compared with women, and systolic blood pressure (SBP) was higher in men. In response to hyperglycemia, cGMP levels did not change in men but did decline in women (Δ−1.10 ± 0.20 vs. Δ+0.05 ± 0.20 pmol/L, between-group effect of hyperglycemia on cGMP; P = 0.012). Hyperglycemia also was associated with an increase in SBP, glomerular filtration rate (GFR) (124 ± 6 to 143 ± 7 mL/min/1.73 m2; P = 0.003) and filtration fraction (FF) in women, but these parameters did not change in men. In response to l-arginine during hyperglycemia, the increase in cGMP was exaggerated in women versus men and GFR and FF decreased in women only, back toward baseline values observed during clamped euglycemia. l-NMMA infusion did not exaggerate changes in hemodynamic function in response to hyperglycemia.CONCLUSIONS l-Arginine reversed the renal hemodynamic effects of hyperglycemia in women, suggesting that nitric oxide is an important regulator of sex-dependent vascular responses to hyperglycemia in humans.

show abstract

“…It was indicated that early diabetic proteinuric nephropathy was associated with increased expression of p47phox component of the reduced form of NADPH oxidase and eNOS with increased H 2 O 2 formation in the kidney, and treatment with an ACE inhibitor or ARB reversed these changes with amelioration of proteinuria [34]. Many studies have shown increased eNOS expression [35,36,37] and eNOS activity [38, 39], especially in kidneys from early stages of diabetes. In this study, histopathological examination showed that eNOS expression in the glomerulus of untreated OLETF rats was increased and that BPS treatment suppressed this expression.…”

Section: Discussionmentioning

confidence: 99%

Amelioration of Diabetic Nephropathy in OLETF Rats by Prostaglandin I<sub>2</sub> Analog, Beraprost Sodium

Watanabe

Nakashima²,

Mochizuki³

et al. 2009

Am J Nephrol

View full text Add to dashboard Cite

Background: Strict control of blood glucose and blood pressure levels sometimes fails to delay the development of diabetic nephropathy, and an effective therapy is not yet available. The present study aimed to examine whether the prostaglandin I₂ analog beraprost sodium (BPS) ameliorates diabetic nephropathy in Otsuka Long-Evans Tokushima Fatty (OLETF) rat. Method: Fifty-week-old OLETF rats were divided into three groups according to treatment; 400 μg/kg body weight (BW) BPS, 200 μg/kg BW BPS, and 0.9% saline administration. Kidney histology, index of glomerulosclerosis, and glomerular volume were determined, and urine and serum chemistry were assessed. Results: The values for urine protein excretion and serum blood urea nitrogen in BPS-treated rats were significantly lower than those in untreated rats. In rats treated with 400 μg/kg BW BPS, neither sclerotic changes nor inflammatory cell infiltration were observed. Index of glomerulosclerosis and glomerular volume were also significantly reduced compared with untreated rats. Intriguingly, BPS reduced the level of serum triglyceride. In the glomerulus of treated rats, advanced glycation end product formation and macrophage influx were suppressed in a dose-dependent manner. Conclusion: These findings indicate that BPS has a therapeutic effect on diabetic nephropathy in the OLETF rat, which suggests a potential application of this drug in the treatment of human diabetic nephropathy.

show abstract

Augmentation of diabetes-associated renal hyperfiltration and nitric oxide production by pregnancy in rats

Cited by 19 publications

References 42 publications

Posttranslational regulation of NO synthase activity in the renal medulla of diabetic rats

Posttranslational regulation of NO synthase activity in the renal medulla of diabetic rats

Sex Differences in Renal Responses to Hyperglycemia, l-Arginine, and l-NMMA in Humans With Uncomplicated Type 1 Diabetes

Amelioration of Diabetic Nephropathy in OLETF Rats by Prostaglandin I<sub>2</sub> Analog, Beraprost Sodium

Contact Info

Product

Resources

About