The Experts below are selected from a list of 1674 Experts worldwide ranked by ideXlab platform

Joseph R. Williamson - One of the best experts on this subject based on the ideXlab platform.

  • Effects of combined insulin and Sorbinil treatment on diabetes-induced vascular dysfunction in rats
    Metabolism: clinical and experimental, 1994
    Co-Authors: Giuseppe Pugliese, Ronald G. Tilton, Amanda Speedy, Peter J. Oates, Joseph R. Williamson
    Abstract:

    These experiments were undertaken to assess the effects of combined treatment with insulin (designed to partially restore metabolic control) and Sorbinil (an aldose reductase inhibitor [ARI]) versus the effects of Sorbinil alone or of two insulin regimens providing different degrees of glycemic control on diabetes-induced metabolic derangements and vascular function. Streptozocin-diabetic rats were divided into the following five groups: (1) untreated (D); (2) treated with approximately 1 U NPH insulin/100 g body weight/d administered in one subcutaneous (SC) injection (DI-1); (3) treated with the same total daily dose of insulin administered in two SC injections (DI-2); (4) treated with approximately 0.2 mmol Sorbinil in the diet/kg body weight/d (DS); and (5) treated with once-daily insulin plus Sorbinil (DSI-1). Two groups of nondiabetic rats, untreated (C) and Sorbinil-treated (CS), served as controls. Metabolic parameters were unaffected by Sorbinil treatment in controls and diabetics, whereas insulin administration in the diabetics virtually normalized body growth, food consumption, urine volume, and plasma glucose levels, and markedly decreased hemoglobin A1 (HbA1) levels. Two daily injections were more effective than one in improving metabolic control as measured by HbA1 levels. Regional vascular 131I-albumin permeation was increased about twofold to threefold by diabetes in ocular tissues, sciatic nerve, aorta, diaphragm, and new granulation tissue; it was decreased (but not normalized) by insulin treatment in accordance with improved metabolic control, and was completely normalized by Sorbinil. 131I-albumin kidney clearance, as well as urinary albumin and IgG excretion, were markedly increased in diabetic rats and were significantly decreased but not completely normalized by Sorbinil and by twice-daily insulin treatment. The combined therapy significantly ameliorated the effect of insulin alone (which still did not completely normalize glucose and HbA1 levels despite prevention of diabetes-induced weight loss and polyuria), although it did not produce an effect on vascular function beyond that of Sorbinil alone (which had no impact on glycemia, HbA1 level, urine volume, or weight gain). These findings suggest that a dual pharmacologic approach, ie, treatment with a combination of insulin, designed to decrease glucose levels (without risking hypoglycemia), and ARIs, to block excess flux of glucose via the sorbitol pathway due to the residual hyperglycemia, may be advantageous for promoting normal growth and metabolism and for preventing vascular complications while minimizing the risk of increased incidence of hypoglycemia.

  • Effects of Sorbinil, Dietary myo-Inositol Supplementation, and Insulin on Resolution of Neuroaxonal Dystrophy in Mesenteric Nerves of Streptozocin-Induced Diabetic Rats
    Diabetes, 1991
    Co-Authors: Robert E. Schmidt, Joseph R. Williamson, Santiago B. Plurad, Bill D. Coleman, Ronald G. Tilton
    Abstract:

    Previous studies indicate that experimental diabetic autonomic neuropathy can be largely prevented by initiating therapy at the onset of diabetes. More clinically relevant, however, is the ability of therapy to reverse established neuropathy produced by long-standing diabetes. We have examined the effect of selected therapies on established neuroaxonal dystrophy (NAD) in ileal mesenteric nerves, a rat model of diabetic autonomic neuropathy. Groups of 3-mo-old rats were made diabetic with streptozocin (STZ-D) and allowed to survive untreated for 5 mo, at which time they were begun on Sorbinil, dietary myo -inositol, and daily insulin therapies or left untreated for an additional 2 or 4 mo. Ultrastructural evidence of NAD was demonstrated in ileal mesenteric nerves of rats with untreated 5-mo STZ-D and increased with the duration of diabetes. No lesions were demonstrated in control rats of any age. myo -inositol or Sorbinil administration failed to alter the severity of diabetes as measured by its metabolic indices. Institution of Sorbinil or insulin treatment at 5 mo of diabetes prevented the increase in, but did not normalize, NAD at 7 or 9 mo. Dietary myo -inositol failed to significantly reverse established NAD or prevent its initial development. Morphometric examination of ileal mesenteric nerves demonstrated a decrease in the number of axons comprising each diabetic Schwann cell unit, suggestive of chronic cycles of axonal degeneration and regeneration. This parameter, clearly abnormal by 5 mo of diabetes, was not normalized by 2 or 4 mo of insulin, Sorbinil, or myo -inositol treatment. These observations indicate that treatment with insulin or an aldose reductase inhibitor, but not myo-inositol, initiated after the development of structural axonopathy significantly inhibited progression of NAD for the duration of treatment. (ABSTRACT TRUNCATED AT 250 WORDS)

  • Discordant effects of the aldose resuctase inhibitor, Sorbinil, on vascular structure and function in chronically diabetic and galactosemic rats
    The Journal of diabetic complications, 1991
    Co-Authors: Ronald G. Tilton, Giuseppe Pugliese, Lorraine S. Larose, Antoinette M. Faller, Katherine Chang, Michael A. Province, Joseph R. Williamson
    Abstract:

    Effects of Sorbinil, an aldose reductase inhibitor, were examined on renal glomerular structure, urinary albumin and IgG excretion, and vascular albumin permeation in eyes and aorta of 8-month diabetic, galactose-fed, and age-matched control rats. Sorbinil was added to the diet of one-half of the rats in each group at the time of induction of diabetes and galactosemia. Weight gain was impaired in diabetic and galactose-fed rats versus controls and was improved slightly in corresponding Sorbinil-treated groups. Plasma glucose and glycosylated hemoglobin levels, food consumption, and 24-hr urine volume were increased in diabetic rats and were unaffected by Sorbinil treatment. Food consumption and glycosylated hemoglobin levels were increased in galactose-fed rats, although the increases were smaller than in diabetic rats; glycosylated hemoglobin levels were decreased by Sorbinil. Diabetes- and galactosemia-induced increases in albumin permeation in eyes and aorta were prevented by Sorbinil. Urinary excretion of albumin and IgG was increased by diabetes and decreased by Sorbinil, although differences between the two diabetic groups were not statistically significant for albumin. Galactosemia was associated with an increase in urinary albumin and IgG excretion that did not reach statistical significance. Glomerular capillary basement membrane width (GBMW) was increased in diabetic versus age-matched control rats but was unaffected by galactose feeding. GBMW was increased in controls fed Sorbinil and glomerular capillary basement membrane thickening in diabetic rats was not prevented by Sorbinil. The fractional volume of the glomerulus occupied by mesangium (Vvmes) was increased in diabetic and galactose fed rats versus age-matched controls, and was unaffected by Sorbinil.(ABSTRACT TRUNCATED AT 250 WORDS)

Ronald G. Tilton - One of the best experts on this subject based on the ideXlab platform.

  • Effects of combined insulin and Sorbinil treatment on diabetes-induced vascular dysfunction in rats
    Metabolism: clinical and experimental, 1994
    Co-Authors: Giuseppe Pugliese, Ronald G. Tilton, Amanda Speedy, Peter J. Oates, Joseph R. Williamson
    Abstract:

    These experiments were undertaken to assess the effects of combined treatment with insulin (designed to partially restore metabolic control) and Sorbinil (an aldose reductase inhibitor [ARI]) versus the effects of Sorbinil alone or of two insulin regimens providing different degrees of glycemic control on diabetes-induced metabolic derangements and vascular function. Streptozocin-diabetic rats were divided into the following five groups: (1) untreated (D); (2) treated with approximately 1 U NPH insulin/100 g body weight/d administered in one subcutaneous (SC) injection (DI-1); (3) treated with the same total daily dose of insulin administered in two SC injections (DI-2); (4) treated with approximately 0.2 mmol Sorbinil in the diet/kg body weight/d (DS); and (5) treated with once-daily insulin plus Sorbinil (DSI-1). Two groups of nondiabetic rats, untreated (C) and Sorbinil-treated (CS), served as controls. Metabolic parameters were unaffected by Sorbinil treatment in controls and diabetics, whereas insulin administration in the diabetics virtually normalized body growth, food consumption, urine volume, and plasma glucose levels, and markedly decreased hemoglobin A1 (HbA1) levels. Two daily injections were more effective than one in improving metabolic control as measured by HbA1 levels. Regional vascular 131I-albumin permeation was increased about twofold to threefold by diabetes in ocular tissues, sciatic nerve, aorta, diaphragm, and new granulation tissue; it was decreased (but not normalized) by insulin treatment in accordance with improved metabolic control, and was completely normalized by Sorbinil. 131I-albumin kidney clearance, as well as urinary albumin and IgG excretion, were markedly increased in diabetic rats and were significantly decreased but not completely normalized by Sorbinil and by twice-daily insulin treatment. The combined therapy significantly ameliorated the effect of insulin alone (which still did not completely normalize glucose and HbA1 levels despite prevention of diabetes-induced weight loss and polyuria), although it did not produce an effect on vascular function beyond that of Sorbinil alone (which had no impact on glycemia, HbA1 level, urine volume, or weight gain). These findings suggest that a dual pharmacologic approach, ie, treatment with a combination of insulin, designed to decrease glucose levels (without risking hypoglycemia), and ARIs, to block excess flux of glucose via the sorbitol pathway due to the residual hyperglycemia, may be advantageous for promoting normal growth and metabolism and for preventing vascular complications while minimizing the risk of increased incidence of hypoglycemia.

  • Effects of Sorbinil, Dietary myo-Inositol Supplementation, and Insulin on Resolution of Neuroaxonal Dystrophy in Mesenteric Nerves of Streptozocin-Induced Diabetic Rats
    Diabetes, 1991
    Co-Authors: Robert E. Schmidt, Joseph R. Williamson, Santiago B. Plurad, Bill D. Coleman, Ronald G. Tilton
    Abstract:

    Previous studies indicate that experimental diabetic autonomic neuropathy can be largely prevented by initiating therapy at the onset of diabetes. More clinically relevant, however, is the ability of therapy to reverse established neuropathy produced by long-standing diabetes. We have examined the effect of selected therapies on established neuroaxonal dystrophy (NAD) in ileal mesenteric nerves, a rat model of diabetic autonomic neuropathy. Groups of 3-mo-old rats were made diabetic with streptozocin (STZ-D) and allowed to survive untreated for 5 mo, at which time they were begun on Sorbinil, dietary myo -inositol, and daily insulin therapies or left untreated for an additional 2 or 4 mo. Ultrastructural evidence of NAD was demonstrated in ileal mesenteric nerves of rats with untreated 5-mo STZ-D and increased with the duration of diabetes. No lesions were demonstrated in control rats of any age. myo -inositol or Sorbinil administration failed to alter the severity of diabetes as measured by its metabolic indices. Institution of Sorbinil or insulin treatment at 5 mo of diabetes prevented the increase in, but did not normalize, NAD at 7 or 9 mo. Dietary myo -inositol failed to significantly reverse established NAD or prevent its initial development. Morphometric examination of ileal mesenteric nerves demonstrated a decrease in the number of axons comprising each diabetic Schwann cell unit, suggestive of chronic cycles of axonal degeneration and regeneration. This parameter, clearly abnormal by 5 mo of diabetes, was not normalized by 2 or 4 mo of insulin, Sorbinil, or myo -inositol treatment. These observations indicate that treatment with insulin or an aldose reductase inhibitor, but not myo-inositol, initiated after the development of structural axonopathy significantly inhibited progression of NAD for the duration of treatment. (ABSTRACT TRUNCATED AT 250 WORDS)

  • Discordant effects of the aldose resuctase inhibitor, Sorbinil, on vascular structure and function in chronically diabetic and galactosemic rats
    The Journal of diabetic complications, 1991
    Co-Authors: Ronald G. Tilton, Giuseppe Pugliese, Lorraine S. Larose, Antoinette M. Faller, Katherine Chang, Michael A. Province, Joseph R. Williamson
    Abstract:

    Effects of Sorbinil, an aldose reductase inhibitor, were examined on renal glomerular structure, urinary albumin and IgG excretion, and vascular albumin permeation in eyes and aorta of 8-month diabetic, galactose-fed, and age-matched control rats. Sorbinil was added to the diet of one-half of the rats in each group at the time of induction of diabetes and galactosemia. Weight gain was impaired in diabetic and galactose-fed rats versus controls and was improved slightly in corresponding Sorbinil-treated groups. Plasma glucose and glycosylated hemoglobin levels, food consumption, and 24-hr urine volume were increased in diabetic rats and were unaffected by Sorbinil treatment. Food consumption and glycosylated hemoglobin levels were increased in galactose-fed rats, although the increases were smaller than in diabetic rats; glycosylated hemoglobin levels were decreased by Sorbinil. Diabetes- and galactosemia-induced increases in albumin permeation in eyes and aorta were prevented by Sorbinil. Urinary excretion of albumin and IgG was increased by diabetes and decreased by Sorbinil, although differences between the two diabetic groups were not statistically significant for albumin. Galactosemia was associated with an increase in urinary albumin and IgG excretion that did not reach statistical significance. Glomerular capillary basement membrane width (GBMW) was increased in diabetic versus age-matched control rats but was unaffected by galactose feeding. GBMW was increased in controls fed Sorbinil and glomerular capillary basement membrane thickening in diabetic rats was not prevented by Sorbinil. The fractional volume of the glomerulus occupied by mesangium (Vvmes) was increased in diabetic and galactose fed rats versus age-matched controls, and was unaffected by Sorbinil.(ABSTRACT TRUNCATED AT 250 WORDS)

Paul H. Yancey - One of the best experts on this subject based on the ideXlab platform.

  • Effects of ascorbic acid, aminoguanidine, Sorbinil and zopolrestat on sorbitol and betaine contents in cultured rat renal cells
    Experimental Biology Online, 1999
    Co-Authors: Jennifer M. Rohr, Steve Truong, Tom Hong, Paul H. Yancey
    Abstract:

    Aldose reductase inhibitors (ARI) have been developed to reduce the conversion of high glucose levels to sorbitol, an important renal osmolyte that may rise to damaging levels in many tissues during diabetic hyperglycemia. Ascorbic acid (AA) and aminoguanidine (AMG) have also been reported to reduce sorbitol levels in diabetes: AMG in rat kidney, and AA in guinea pig lens and human erythrocytes. We tested the effects of AMG, AA, and Pfizer’s Sorbinil and zopolrestat for 48 h on primary rat renal cell cultures, established from renal inner medullas of male Wistar rats 8–12 weeks old. Osmolyte contents in scraped cells were analysed by HPLC: 100 µM Sorbinil and 20 µM zopolrestat decreased sorbitol levels ( P

  • Time-dependent aspects of osmolyte changes in rat kidney, urine, blood and lens with Sorbinil and galactose feeding
    Kidney international, 1995
    Co-Authors: Scott D. Edmands, Karin S. Hughs, Young Lee, Suzann D. Meyer, Edwin Saari, Paul H. Yancey
    Abstract:

    Time-dependent aspects of osmolyte changes in rat kidney, urine, blood and lens with Sorbinil and galactose feeding. Sorbitol plus myo -inositol, betaine and glycerophosphorylcholine (GPC) are cellular osmolytes in the mammalian renal medulla. Galactosemia and hyperglycemia can cause excessive levels of galactitol or sorbitol in several organs via aldose reductase (AR) catalysis. AR inhibitors can reduce these polyols. To examine osmolyte responses to polyol perturbations, male Wistar rats were fed normal diet, the AR inhibitor Sorbinil (at 40 mg/kg/d), 25% galactose, or a combination, for 10, 21 and 42 days. All animals at 21 days had higher apparent renal AR activity than at 10 or 42 days, possibly providing resistance to Sorbinil. Sorbinil feeding alone tended to increase urinary, plasma and renal urea levels. It reduced AR activity and sorbitol contents in renal inner medulla, though less so at 21 days; other renal osmolytes, especially betaine, were elevated. Galactose feeding caused little change in renal AR activity, and resulted in high galactose and galactitol contents in renal medulla, urine, blood and lens (and higher renal Na + contents at 10 days). Renal sorbitol, inositol and GPC decreased, while betaine contents trended higher at all times. Sorbinil-galactose feeding reduced renal AR activities and galactitol contents (again less so at 21 days), urine, blood and lens galactitol, and further reduced renal sorbitol contents. At 10 and 21 days it tended to raise renal betaine more, and restore inositol (but not GPC) contents to control levels. At 42 days it reduced renal and urinary Na + and galactose, and decreased renal betaine to control levels. Under most conditions, total renal (non-urea) organic osmolyte contents (presumed to be mostly intracellular) and Na + plus galactose contents (presumed mostly extracellular) changed together such that cell volumes may have been maintained. The exception was 10 days on galactose, where total osmolytes appeared too low. In galactose-fed animals, urine/plasma ratios suggest some renal galactitol efflux, and cellular galactitol probably helps maintain osmotic balance rather than cause swelling.

Giuseppe Pugliese - One of the best experts on this subject based on the ideXlab platform.

  • Effects of combined insulin and Sorbinil treatment on diabetes-induced vascular dysfunction in rats
    Metabolism: clinical and experimental, 1994
    Co-Authors: Giuseppe Pugliese, Ronald G. Tilton, Amanda Speedy, Peter J. Oates, Joseph R. Williamson
    Abstract:

    These experiments were undertaken to assess the effects of combined treatment with insulin (designed to partially restore metabolic control) and Sorbinil (an aldose reductase inhibitor [ARI]) versus the effects of Sorbinil alone or of two insulin regimens providing different degrees of glycemic control on diabetes-induced metabolic derangements and vascular function. Streptozocin-diabetic rats were divided into the following five groups: (1) untreated (D); (2) treated with approximately 1 U NPH insulin/100 g body weight/d administered in one subcutaneous (SC) injection (DI-1); (3) treated with the same total daily dose of insulin administered in two SC injections (DI-2); (4) treated with approximately 0.2 mmol Sorbinil in the diet/kg body weight/d (DS); and (5) treated with once-daily insulin plus Sorbinil (DSI-1). Two groups of nondiabetic rats, untreated (C) and Sorbinil-treated (CS), served as controls. Metabolic parameters were unaffected by Sorbinil treatment in controls and diabetics, whereas insulin administration in the diabetics virtually normalized body growth, food consumption, urine volume, and plasma glucose levels, and markedly decreased hemoglobin A1 (HbA1) levels. Two daily injections were more effective than one in improving metabolic control as measured by HbA1 levels. Regional vascular 131I-albumin permeation was increased about twofold to threefold by diabetes in ocular tissues, sciatic nerve, aorta, diaphragm, and new granulation tissue; it was decreased (but not normalized) by insulin treatment in accordance with improved metabolic control, and was completely normalized by Sorbinil. 131I-albumin kidney clearance, as well as urinary albumin and IgG excretion, were markedly increased in diabetic rats and were significantly decreased but not completely normalized by Sorbinil and by twice-daily insulin treatment. The combined therapy significantly ameliorated the effect of insulin alone (which still did not completely normalize glucose and HbA1 levels despite prevention of diabetes-induced weight loss and polyuria), although it did not produce an effect on vascular function beyond that of Sorbinil alone (which had no impact on glycemia, HbA1 level, urine volume, or weight gain). These findings suggest that a dual pharmacologic approach, ie, treatment with a combination of insulin, designed to decrease glucose levels (without risking hypoglycemia), and ARIs, to block excess flux of glucose via the sorbitol pathway due to the residual hyperglycemia, may be advantageous for promoting normal growth and metabolism and for preventing vascular complications while minimizing the risk of increased incidence of hypoglycemia.

  • Discordant effects of the aldose resuctase inhibitor, Sorbinil, on vascular structure and function in chronically diabetic and galactosemic rats
    The Journal of diabetic complications, 1991
    Co-Authors: Ronald G. Tilton, Giuseppe Pugliese, Lorraine S. Larose, Antoinette M. Faller, Katherine Chang, Michael A. Province, Joseph R. Williamson
    Abstract:

    Effects of Sorbinil, an aldose reductase inhibitor, were examined on renal glomerular structure, urinary albumin and IgG excretion, and vascular albumin permeation in eyes and aorta of 8-month diabetic, galactose-fed, and age-matched control rats. Sorbinil was added to the diet of one-half of the rats in each group at the time of induction of diabetes and galactosemia. Weight gain was impaired in diabetic and galactose-fed rats versus controls and was improved slightly in corresponding Sorbinil-treated groups. Plasma glucose and glycosylated hemoglobin levels, food consumption, and 24-hr urine volume were increased in diabetic rats and were unaffected by Sorbinil treatment. Food consumption and glycosylated hemoglobin levels were increased in galactose-fed rats, although the increases were smaller than in diabetic rats; glycosylated hemoglobin levels were decreased by Sorbinil. Diabetes- and galactosemia-induced increases in albumin permeation in eyes and aorta were prevented by Sorbinil. Urinary excretion of albumin and IgG was increased by diabetes and decreased by Sorbinil, although differences between the two diabetic groups were not statistically significant for albumin. Galactosemia was associated with an increase in urinary albumin and IgG excretion that did not reach statistical significance. Glomerular capillary basement membrane width (GBMW) was increased in diabetic versus age-matched control rats but was unaffected by galactose feeding. GBMW was increased in controls fed Sorbinil and glomerular capillary basement membrane thickening in diabetic rats was not prevented by Sorbinil. The fractional volume of the glomerulus occupied by mesangium (Vvmes) was increased in diabetic and galactose fed rats versus age-matched controls, and was unaffected by Sorbinil.(ABSTRACT TRUNCATED AT 250 WORDS)

Russ Chess-williams - One of the best experts on this subject based on the ideXlab platform.

  • The effect of Sorbinil, an aldose reductase inhibitor, on aortic function in control and streptozotocin-induced diabetic rats.
    Journal of autonomic pharmacology, 2000
    Co-Authors: Donna J Sellers, Russ Chess-williams
    Abstract:

    1. The present study investigates the effect of treatment of 14-day streptozotocin-diabetic rats with the aldose reductase inhibitor, Sorbinil, on changes ex vivo in aortic vasoconstriction and vasodilation. 2. Maximum contractile responses and aortic sensitivity to phenylephrine were significantly enhanced in aortae from 14-day diabetic rats, in accordance with our previous data. 3. Endothelium-dependent relaxations to carbachol were, in contrast, depressed, although endothelium-independent relaxations to forskolin and sodium nitroprusside were unaltered. 4. Sorbinil treatment of diabetic animals failed to prevent any of these diabetes-induced alterations in aortic function, and indeed exacerbated some of these alterations. In addition, Sorbinil treatment caused altered aortic responses in control animals, which sometimes mirrored those found in diabetic animals. 5. It can be concluded that Sorbinil may have actions in addition to, and independent of, polyol pathway inhibition. Thus, Sorbinil may not be an effective tool for the investigation of aldose reductase inhibition within the vascular system of the rat.

  • The effects of streptozotocin-induced diabetes and aldose reductase inhibition with Sorbinil, on left and right atrial function in the rat
    The Journal of pharmacy and pharmacology, 2000
    Co-Authors: Donna J Sellers, Russ Chess-williams
    Abstract:

    Diabetes mellitus is frequently associated with the complications of cardiovascular disease. Activation of the aldose reductase (or polyol) pathway has long been implicated as an underlying factor for the development of many diabetic complications and indeed, treatment with aldose reductase inhibitors has been shown to prevent or reverse many of these diabetic complications. This study examines the effects of 14-day streptozotocin-induced diabetes on alpha1- and beta-adrenoceptor-mediated responses in rat isolated left and right atria. The effects of treatment with the aldose reductase inhibitor (ARI) Sorbinil were also studied. A positive inotropic response was observed to both isoprenaline and phenylephrine in left atria. Diabetes of 14 days duration resulted in a supersensitivity of these tissues to the beta-adrenoceptor agonist in comparison with controls, while responses to the alpha1-adrenoceptor agonist were unaltered. Spontaneously beating right atria from diabetic rats was found to have a depressed resting rate compared with control tissues, although positive chronotropic beta-adrenoceptor-mediated responses were not affected by diabetes. Phenylephrine produced alpha1-adrenoceptor-mediated chronotropic responses in right atrial tissues, and these were found to be enhanced in rats with diabetes. Treatment of diabetic rats with the ARI Sorbinil was successful in preventing only one of the observed diabetes-induced changes in atrial function, namely the supersensitivity of left atria to isoprenaline. Sorbinil treatment did, however, alter responses of control left and right atria in a manner similar to diabetes. In conclusion, streptozotocin-induced diabetes of 14 days duration was found to cause a number of alterations in the functioning of both left and right atria. ARI treatment with Sorbinil failed to prevent all but one of these changes, and in addition altered responses of atria from control rats, having a similar effect to that produced by diabetes. These data suggest that Sorbinil may have effects in addition to, and independent of, aldose reductase inhibition in the cardiovascular system.