Effect of captopril on skeletal muscle angiogenic growth factor responses to exercise.

Acute exercise increases vascular endothelial growth factor (VEGF), transforming growth factor-beta(1) (TGF-beta(1)), and basic fibroblast growth factor (bFGF) mRNA levels in skeletal muscle, with the greatest increase in VEGF mRNA. VEGF functions via binding to the VEGF receptors Flk-1 and Flt-1. Captopril, an angiotensin-converting enzyme inhibitor, has been suggested to reduce the microvasculature in resting and exercising skeletal muscle. However, the molecular mechanisms responsible for this reduction have not been investigated. We hypothesized that this might occur via reduced VEGF, TGF-beta(1), bFGF, Flk-1, and Flt-1 gene expression at rest and after exercise. To investigate this, 10-wk-old female Wistar rats were placed into four groups (n = 6 each): 1) saline + rest; 2) saline + exercise; 3) 100 mg/kg ip captopril + rest; and 4) 100 mg/kg ip captopril + exercise. Exercise consisted of 1 h of running at 20 m/min on a 10 degrees incline. VEGF, TGF-beta(1), bFGF, Flk-1, and Flt-1 mRNA were analyzed from the left gastrocnemius by quantitative Northern blot. Exercise increased VEGF mRNA 4.8-fold, TGF-beta(1) mRNA 1.6-fold, and Flt-1 mRNA 1.7-fold but did not alter bFGF or Flk-1 mRNA measured 1 h after exercise. Captopril did not affect the rest or exercise levels of VEGF, TGF-beta(1), bFGF, and Flt-1 mRNA. Captopril did reduce Flk-1 mRNA 30-40%, independently of exercise. This is partially consistent with the suggestion that captopril may inhibit capillary growth.

Nitric oxide synthase inhibition attenuates the skeletal muscle VEGF mRNA response to exercise.

Vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and transforming growth factor-beta(1) (TGF-beta(1)) mRNA increase in rat skeletal muscle in response to a single acute exercise bout. Nitric oxide (NO) is released locally by muscle vascular endothelium and muscle fibers during exercise, contributes to the blood flow response to exercise, and regulates mitochondrial respiration. We hypothesized that a reduction in NO production, via NO synthase inhibition, would demonstrate a link between NO and the VEGF, bFGF, and TGF-beta(1) gene responses to exercise. To investigate this hypothesis, 9-wk-old female Wistar rats were divided into eight treatment groups (n = 6 each): 1) saline + rest, 2) saline + exercise, 3) 30 mg/kg N(omega)-nitro-L-arginine methyl ester (L-NAME, a known NOS inhibitor) + rest, 4) 30 mg/kg L-NAME + exercise, 5) 300 mg/kg L-NAME + rest, 6) 300 mg/kg L-NAME + exercise, 7) 300 mg/kg N(omega)-nitro-D-arginine methyl ester (D-NAME, inactive enantiomer of L-NAME) + rest, and 8) 300 mg/kg D-NAME + exercise. Exercise consisted of 1 h of running at 20 m/min on a 10 degrees incline. VEGF, TGF-beta(1), and bFGF mRNA from left gastrocnemius were analyzed by quantitative Northern blot. Submaximal exercise for 1 h increased VEGF mRNA 4.2-fold and TGF-beta(1) mRNA 1.5-fold in untreated rats but did not increase bFGF mRNA. The exercise-induced increase in VEGF mRNA was attenuated approximately 50% by 30 and 300 mg/kg L-NAME; the TGF-beta(1) mRNA increase was unaffected by 300 mg/kg L-NAME. In addition, 300 mg/kg D-NAME had no effect on the exercise-induced increase in VEGF mRNA. Administration of 300 mg/kg L-NAME had no effect on bFGF mRNA. These findings suggest that NO is important in the regulation of the VEGF gene response to exercise through increases in VEGF transcription or by increases in the VEGF mRNA half-life.

Effect of phosphorus restriction on renal response to oral and intravenous protein loads in rats.

Dietary phosphorus restriction ameliorates renal injury in rats. This may be due to changes in renal hemodynamics, including those factors associated with protein-induced hyperfiltration. To test this, we measured inulin clearance (CIn), p-aminohippuric acid clearance (CPAH), mean arterial blood pressure, and renal vascular resistance (RVR) 1 h before and 100 min after either oral gavage of 2 g bovine serum albumin or intravenous infusion of 5% glycine in female Sprague-Dawley rats previously fed for 3-8 wk a 0.5% or a 0.1% phosphorus diet. Baseline CIn, CPAH, blood pressure, and RVR were similar. After albumin gavage, CIn rose 20% (P < 0.01) for the 0.5% phosphorus group but did not change for rats fed the 0.1% phosphorus diet. Other measured parameters, including plasma glucagon and renin activity, were not influenced by dietary phosphorus content. In contrast, during intravenous infusion of glycine, hyperfiltration was induced in phosphorus-restricted rats. Thus dietary phosphorus restriction ablates oral protein but not intravenous amino acid-induced hyperfiltration, suggesting a gut-mediated mechanism for the former. These data highlight the potential importance of dietary phosphorus as a mediator of renal hemodynamics.

Peritoneal dialysis catheter outflow obstruction due to oviductal fimbriae: a case report.

Outflow obstruction is a common cause of peritoneal dialysis catheter malfunction. We report an unusual case of outflow obstruction caused by oviductal fimbriae. Mini-laparatomy and repositioning of the catheter without excising the fallopian tube resulted in good outcome.

Acute non-dilating obstructive renal failure in a patient with AIDS.

A 30-year-old male who presented with acute renal failure was found to have acquired immunodeficiency syndrome (AIDS). Although sonography and computerized tomography did not show urinary tract dilatation, obstructive renal failure was demonstrated by retrograde pyelography. Relief of obstruction(s) due to encasement of the renal pelves and ureters with histiocytic lymphoma led to immediate return of normal renal function. Although the etiology of renal failure in this patient is highly unusual, the high incidence of lymphoma in patients with AIDS should make tumor-related renal disease a consideration in all such patients with renal dysfunction.

Characteristics and sequelae of peritonitis in diabetics and nondiabetics receiving chronic intermittent peritoneal dialysis.

To evaluate the effect of diabetic status upon peritoneal dialysis-associated peritonitis, the characteristics and sequelae of 159 episodes of peritonitis were reviewed in 26 diabetic and 59 nondiabetic peritoneal dialysis patients. There was no difference between the two patient groups in peritonitis occurrence rates or in individual patient attack rate. The spectra of etiologic florae were comparable, although the nondiabetic group had a greater incidence of Staphylcoccus aureus and fungal peritonitis. Presenting symptomatology, ascitic fluid characteristics, duration of illness, and sequelae of peritonitis, including catheter loss and death, were similar in diabetics and nondiabetics. Dialysis peritonitis is manifested by a spectrum of illness ranging from brief asymptomatic infection to painful prolonged disease; however, the latter course is not more common in diabetics. Further, in diabetics, peritonitis is neither a more frequent event, nor inherently a greater risk, than in nondiabetics.

Comparison of pituitary-thyroid function in patients with endstage renal disease and in age- and sex-matched controls.

The response to i.v. bolus thyrotropin-releasing hormone (TRH) of 14 dialysis patients with end-stage renal disease (ESRD) was compared to the response of 14 age- and sex-matched renal clinic patients (controls) with normal renal function (serum creatinine concentrations less than 1.2 mg/dl). The mean basal serum levels of thyrotropin (TSH) were similar in the two groups. There was no difference between the two groups in the mean maximal increase in TSH after TRH (6.3 microU/ml and 7.2 microU/ml in ESRD and control groups, respectively); The rate of fall in TSH from 60 to 90 min after TRH was slower in the ESRD group than in the controls. The mean increase in serum triiodothyronine (T3) concentration after TRH was similar in both groups (25.4 ng/dl, ESRD; 18.4 ng/dl, controls). As previously reported, basal serum T3 content was subnormal in the ESRD patients. Serum thyroxine (T4) concentrations were comparable in control and ESRD groups and did not change significantly during the 90-min TRH test in either group. We conclude that ESRD patients, clinically stable on dialysis, have normal pituitary TRH responsiveness and normal thyroidal response to endogenous TSH secretion, as compared with an age- and sex-matched group of patients with normal renal function. The results of this study support the contention that ESRD patients are eumetabolic.

Glomerulonephritis and Staphylococcal aureus infections.

Three patients with visceral Staphylococcal aureus infections, but no evidence of endocarditis, developed signs of acute glomerulonephritis. Renal biopsy in two patients showed a mesangial proliferative glomerulonephritis and mesangial deposits containing IgA, IgG, and C3; autopsy material in a third patient showed acute diffuse proliferative glomerulonephritis. The clinical setting and pathologic findings of our patients with visceral Staphylococcal infection and glomerulonephritis are different than those found in the better-understood syndromes of glomerulonephritis associated with endocarditis or infected ventriculojugular shunts. Our patients provide support for the contention that some cases of primary or idiopathic glomerulonephritis may by caused by Staphylococcal infections.

Thyroid function and metabolic state in chronic renal failure.

Thirty-eight patients with chronic renal insufficiency who were in a dialysis program underwent studies of thyroid function and metabolic status. Mean values for serum total and free thyroxine (T4) concentrations and thyroxine-binding globulin capacity were within normal limits. Although mean serum total triiodothyronine (T3) concentration was normal, 43% of the group had low serum T3 and 54% had low serum free T3 concentrations. Serum thyrotrophin (TSH) concentrations were normal in all but four subjects who had very slight elevations. Metabolic status was assessed by various metabolic tests; mean values for each of these tests were normal, and the clinical index scores indicated that all patients were euthyroid. Results of metabolic testing were similar in patients with low and those with normal serum T3 concentrations. Low serum T3 measurements did not accurately reflect metabolic state in patients with chronic renal failure, whereas serum free T4 and TSH concentrations were reliable indicators of thyroid state.