Expression of nitric oxide synthase in macula densa in streptozotocin diabetic rats

Yagihashi, Norito; Nishida, Naoki; Seo, Han Geuk; Taniguchi, N; Yagihashi, Soroku

doi:10.1007/s001250050512

Cited by 36 publications

(27 citation statements)

References 48 publications

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“…To the best of our knowledge, several previous studies have explored nNOS renalexpression in diabetes. Supporting our findings, Yagihashi et al [30] reported less intense immunohistochemical staining for cyclic NOS (presumably nNOS) in MD and glomerular arterioles in rats with various durations of diabetes. In contrast, Choi et al [31] and Komers et al [17] found a marked increase in cortical nNOS in STZ-diabetic rats, as assessed by Western blotting and immunohistochemistry, respectively.…”

Section: Discussionsupporting

confidence: 77%

Role of Renal Nitric Oxide Synthase in Diabetic Kidney Disease during the Chronic Phase of Diabetes

Khamaisi¹,

Keynan²,

Bursztyn³

et al. 2006

Nephron Physiol

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Background: Several studies have suggested that an early increase in renal nitric oxide (NO) production or activity mediates pathophysiologic and morphologic changes in diabetic nephropathy. To evaluate the role of NO in developing diabetic kidney disease, we studied the NO system in streptozotocin (STZ)-induced diabetic rats for a period of 8 weeks. Methods: Control rats, STZ-induced diabetic rats, and STZ-induced diabetic rats treated with insulin were monitored and sacrificed at 1, 2, and 8 weeks. Urinary cGMP was measured, and the levels and activity of NO synthase (NOS) isoforms in the kidney cortex were determined at specific times by immunoblotting and diaphorase staining. Results: Diabetic rats had increased kidney weight, urinary volume, glucose, sodium and potassium excretion, which was precluded by insulin treatment. Creatinine clearance was increased in the diabetic group and reversed by insulin treatment. Urinary cGMP decreased by 71, 93, and 92% at 1, 2, and 8 weeks of diabetes, respectively, compared with the control animals. Insulin treatment curtailed the urinary cGMP reduction in diabetic animals. Total NOS activity in the renal cortex was reduced by 65, 52, and 44% after 1, 2, and 8 weeks of diabetes, respectively, and returned to normal levels upon insulin treatment. NADPH diaphorase staining of renal cortical slices showed a 77, 63, and 70% decrease in neuronal NOS isoform activity in the macula densa after 1, 2, and 8 weeks of diabetes, respectively, compared with control non-diabetic animals. This reduction was normalized by insulin treatment. Endothelial NOS protein expression in the kidney cortex tended to increase after 1 week of diabetes and its level was elevated significantly after 2 and 8 weeks of diabetes. However, neuronal NOS protein expression in the kidney cortex was reduced by 52% in 2-week diabetic animals, but this reduction was normalized by insulin treatment. Conclusions: The decreased renal NOS activity during the late phase of diabetes is partially associated with a decrease in neuronal NOS activity and protein expression in kidney macula densa.

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Section: Discussionsupporting

confidence: 77%

Role of Renal Nitric Oxide Synthase in Diabetic Kidney Disease during the Chronic Phase of Diabetes

Khamaisi¹,

Keynan²,

Bursztyn³

et al. 2006

Nephron Physiol

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“…Yagihashi et al 16 showed decreased immunoreactivity of nNOS in the macula densa and glomerular arterioles in diabetic rats. Similarly, in another study, it was shown that kidney nNOS activity decreased and protein levels were significantly lowered in STZ diabetic animals.…”

Section: Discussionmentioning

confidence: 97%

Ameliorative effects of pentoxifylline on NOS induced by diabetes in rat kidney

Sönmez

Dündar

2016

Renal Failure

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Objectives Diabetic nephropathy (DN) is the leading cause of end-stage renal disease worldwide. The NO system has been implicated in the pathogenesis of DN. In this study, we aimed to evaluate the healing effect of pentoxifylline on NOS in STZ-induced diabetic rat's kidney. Material and methods In this study, 50 Wistar albino male rats were used. The rats were divided into five groups; Group C control; Group D only diabetes; Group D + PI and D + PII diabetes + pentoxifylline; Group P only pentoxifylline. Group DPI rats received just pentoxifylline from the beginning of the experiments. However, Group DPII rats received saline in the first month and 50 mg/kg/day of pentoxifylline for the following month. At the end of two months, NOS expressions in kidney tissue were assessed using qRT-PCR and immunohistochemistry analysis. Results At the end of the experiments, desquamation of the epithelial cells of the tubules, clear glycogen-filled distal tubules and increased number of apoptotic cells were seen in Group D. Diabetic rats' nNOS immunoreactivity had increased and eNOS and iNOS immunoreactivity had decreased; nNOS, iNOS and eNOS mRNA levels tended to decrease compared to the control group. PTX ameliorated eNOS, iNOS and nNOS protein levels and apoptotic cells, but did not affect mRNA levels. Conclusion In conclusion, PTX has a healing effect on this damage by affecting NOS expression. ARTICLE HISTORY

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“…Diaphorase staining and immunohistochemical staining suggest reduced NOS activity in sympathetic autonomic ganglia 165 and macula densa 166 of experimental diabetic rats. Another study revealed a decrease in mRNA and content of neuronal NOS (nNOS) in diabetic penile tissue.…”

Section: Measurement Of Nos Protein Mrna or Activitymentioning

confidence: 91%

Review of Alterations in Endothelial Nitric Oxide Production in Diabetes

1998

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N itric oxide release from the endothelium plays an important role in regulation of vascular tone, 1 inhibition of both platelet and leukocyte aggregation and adhesion, 1,2 and inhibition of cell proliferation.3 These properties suggest that the level of NO production by the endothelium may play a pivotal role in the regulation of vascular disease. Analysis using mass spectrometry has revealed that NO is produced by NOS from the terminal guanidino nitrogen of the precursor amino acid L-arginine. 4 Thus, utilization of L-arginine and conversion to NO may establish a regulatory site in the development of endothelial dysfunction.Endothelial dysfunction is characterized by defective endothelium-dependent relaxation, and some reviews regarding endothelial dysfunction in diabetes have been published. [5][6][7][8] These reviews have focused on factors that might contribute to defective relaxation, some of which will not be addressed in detail in this review. The purpose of the present review is to summarize evidence that specifically supports either decreased NO production by diabetic vascular endothelium and/or impaired NO-mediated endothelium-dependent relaxation. Second, this review provides reasonable alternatives to explain some of the controversies in this research area. Third, since there is growing evidence that arginine appears to have some benefits for diabetes-associated abnormalities, this review summarizes the current state of knowledge of effects of acute and chronic administration of L-arginine on diabetesinduced endothelial dysfunction and discusses potential NOdependent and -independent mechanisms whereby therapeutic intervention with L-arginine might benefit the diabetic endothelium. Impaired Endothelium-Dependent Relaxation Experimental Diabetes MellitusDecreases in endothelium-dependent relaxation are a common feature in both conduit 9 -20 and resistance 21-30 arteries of chemically induced experimental diabetic animals (including rats, mice, rabbits, hamsters, and dogs). In two genetic models of IDDM, similar impaired relaxation has been documented in aorta [31][32][33] and mesenteric arteries 34,35 of diabetes-prone BB/Wor or BB/E rats and in aorta 36 and mesenteric arteries 37 of the diabetes-prone WBN/Kob rat. Almost without exception, studies that have shown impaired endothelium-dependent relaxation have found normal relaxation to nitrovasodilators. These agents relax vascular smooth muscle by activating guanylate cyclase but, unlike NO, do not require the presence of the endothelium. Thus, the intrinsic property to activate vascular smooth muscle guanylate cyclase appears not to be altered by experimental diabetes.Studies in experimental models of NIDDM are few and controversial. In the obese Zucker rat, no alteration in endothelium-dependent relaxation has been observed in intestinal microvessels, 38 whereas increased reactivity has been observed in aorta. 39,40 In contrast, decreased endotheliumdependent relaxation to acetylcholine but not to A23187 was seen in aorta in male (but not female)...

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Expression of nitric oxide synthase in macula densa in streptozotocin diabetic rats

Cited by 36 publications

References 48 publications

Role of Renal Nitric Oxide Synthase in Diabetic Kidney Disease during the Chronic Phase of Diabetes

Role of Renal Nitric Oxide Synthase in Diabetic Kidney Disease during the Chronic Phase of Diabetes

Ameliorative effects of pentoxifylline on NOS induced by diabetes in rat kidney

Review of Alterations in Endothelial Nitric Oxide Production in Diabetes

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