Effects of indomethacin on glomerular hemodynamics in experimental diabetes

Jensen, Patricia; Steven, Kenneth; Blaehr, Hanne; Christiansen, Jens Sandahl; Parving, Hans‐Henrik

doi:10.1038/ki.1986.26

Cited by 91 publications

(40 citation statements)

References 19 publications

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“…This hyperfiltration is mainly caused by an elevated glomerular plasma flow rate and increased glomerular capillary pressure (even in the presence of normal systemic blood pressure) (3,(6)(7)(8)(9). Glomerular hypertension may be important in initiation and progression of diabetic nephropathy (10); consequently, several studies have attempted to discern the factors leading to glomerular hypertension in early diabetes.…”

Section: Introductionmentioning

confidence: 99%

“…The early stages ofboth clinical and experimental diabetes mellitus (1)(2)(3)(4)(5)(6)(7)(8)(9) are characterized by an increase in the GFR. This hyperfiltration is mainly caused by an elevated glomerular plasma flow rate and increased glomerular capillary pressure (even in the presence of normal systemic blood pressure) (3,(6)(7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

“…Indeed, when insulin was infused into diabetic rats whose plasma glucose concentration was clamped at hyperglycemic levels, it lowered glomerular capillary pressure without affecting systemic blood pressure (7). In addition, the glomeruli are known to possess abundant insulin receptors ( 1 [1][2][3][4][5][6][7][8][9][10][11][12][13][14] that could mediate actions besides glucose transport as in other vascular beds (15)(16)(17)(18)(19)(20)(21). Taken together, these findings suggest that insulin per se could be an important regulator of glomerular capillary pressure.…”

Section: Introductionmentioning

confidence: 99%

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Disparate effects of insulin on isolated rabbit afferent and efferent arterioles.

Juncos¹,

Ito²

1993

J. Clin. Invest.

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Despite evidence that insulin per se may be an important regulator of glomerular hemodynamics, little is known about its direct action on the glomerular afferent arterioles (Af-Art) and efferent arterioles (Ef-Art), the crucial vascular segments that control glomerular hemodynamics. In the present study, we examined the direct effect of physiological concentrations of insulin on isolated microperfused rabbit Af-and Ef-Arts. After cannulation, vessels were equilibrated in insulin-free medium for 30 min. To determine whether insulin causes vasodilation or constriction, increasing doses (5, 20, and 200 ,U/ml) were added to the bath and lumen of arterioles that were either preconstricted to 50% of control diameter with norepinephrine or left nonpreconstricted. Insulin caused no vasoconstriction in either Af-or Ef-Arts, but it reversed norepinephrine-induced constriction in Ef-Arts but not Af-Arts (suggesting a vasodilator action selective to the Ef-Art): at 200 MU/ml, insulin increased Ef-Art luminal diameter by 75.8±7.0% from the preconstricted level (n = 6; P < 0.008). The vasorelaxant effect of insulin on Ef-Arts was not affected by blockade of either endotheliumderived relaxing factor/nitric oxide or prostaglandin synthesis. Despite the lack of effect of insulin on Af-Art when added after the equilibration period, when Af-Arts were equilibrated in the presence of either 20 or 200 MU/ml insulin, their basal diameter was significantly reduced (11.7±0.9 ,m; P < 0.025, n = 6, and 12.0±0.9 Mm; P < 0.025, n = 7, respectively) compared with nontreated Af-Arts (16.2±1.3 Am; n = 7). In conclusion, this study demonstrates that at physiological concentrations, insulin dilates NE-constricted Ef-Arts, while insulin pretreatment enhances Af-Art tone. The disparate actions of insulin on the Af-vs the Ef-Art may contribute to its beneficial effect on glomerular hypertension. (J. Clin. Inwest. 1993. 92:1981

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Disparate effects of insulin on isolated rabbit afferent and efferent arterioles.

Juncos¹,

Ito²

1993

J. Clin. Invest.

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“…Another 15 patients without a prior observation period and a U,~b/U .... t ratio > 1.0 received the same amount of dipyridamole for 9 months, resulting in a decrease in the U,~b/U .... ~ ratio of 0. 43 …”

Section: Future Trends and Perspectives In Treating Diabetic Nephropathymentioning

confidence: 99%

“…In experimental diabetes using STZ diabetic rats, the administration of indomethacin an inhibitor of prostaglandin synthesis, leads to an increase in the afferent arteriolar hydraulic resistance and a moderate increase in the efferent resistance causing a reduction in the hydraulic pressure in the glomerular capillaries [43]. In a small randomized double-blind trial the effects of 150 mg/day indomethacin for 3 days were studied in 8 patients with IDDM and microalbuminuria, who were compared with a placebo group of 9 normoalbuminuric IDDM patients and 11 healthy controls [44].…”

Section: Future Trends and Perspectives In Treating Diabetic Nephropathymentioning

confidence: 99%

Current therapeutic management of diabetic nephropathy

Köhler

Krämer

1994

Acta Diabetol

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Abstract. Roughly 40% of all patients with insulin-dependent diabetes mellitus (IDDM) develop diabetic nephropathy with proteinuria, hypertension and a decrease in glomerular filtration rate 10 to 20 years after the onset of the disease, and 5 years later most patients suffer from end-stage renal disease. Microalbuminuria, defined as an urinary albumin excretion rate (UAER) between 30 and 300 mg/day, strongly predicts the development of nephropathy in IDDM. Nearly all patients with IDDM, a decreasing glomerular filtration rate and a UAER > 300 mg/day have coexisting hypertensive disease additionally worsening renal function. We review the results of recent long-term studies of the current therapeutic management in diabetic patients by means of better blood pressure control, low-protein diet and near-normal blood glucose control in the early microalbuminuric phase as well as in the later phases of the disease characterized by diabetic nephropathy with a UAER > 300 mg/day. Since the large majority of studies have been performed on IDDM, our conclusions with regard to therapy are only valid in this subgroup of diabetic patients.

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Promotion, prediction and prevention of progression of nephropathy in Type 1 diabetes mellitus

Rossing

1998

Diabet. Med.

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The scope of the present review is to discuss the prognosis of diabetic renal disease, putative progression promoters and the possibilities for treatment and prediction of treatment efficacy. The recent changes in the incidence of diabetic nephropathy in Type 1 diabetes mellitus are discussed. Promoters of progression in diabetic nephropathy are evaluated, in particular arterial blood pressure, glycaemic control, albuminuria and cholesterol levels. Potential treatment modalities are discussed, with special focus on antihypertensive therapy, including a discussion of a specific renoprotective action of certain antihypertensive agents. Furthermore putative predictors of treatment efficacy are evaluated, demonstrating that the ability to lower the urinary albumin excretion rate after onset of treatment heralds a slow progression of the renal disease. The prognosis in diabetic renal disease has improved with an increase in median survival after onset of nephropathy from 6 to 15 years. This has exposed the importance of cardiovascular morbidity and mortality. The identification and treatment of cardiovascular risk factors has become essential. Although the prognosis has improved remarkably, the primary goal should be prevention of diabetic nephropathy, as it is unlikely that the increased risks associated with this complication can be eliminated.

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Effects of indomethacin on glomerular hemodynamics in experimental diabetes

Cited by 91 publications

References 19 publications

Disparate effects of insulin on isolated rabbit afferent and efferent arterioles.

Disparate effects of insulin on isolated rabbit afferent and efferent arterioles.

Current therapeutic management of diabetic nephropathy

Promotion, prediction and prevention of progression of nephropathy in Type 1 diabetes mellitus

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