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Biomedical subjects

T W Meyer

Publications and source records attributed to T W Meyer.

At least 19 recordsLinked to original sources
PubMed1992

Angiotensin II receptor blockade limits glomerular injury in rats with reduced renal mass.

The effects of angiotensin II (AII) blockade were compared with the effects of angiotensin converting enzyme inhibition in rats with reduced nephron number. Rats were subjected to five-sixths renal ablation and divided into four groups with similar values for blood pressure and serum creatinine after 2 wk. Group 1 then served as untreated controls, while group 2 received the AII receptor antagonist MK954 (which has previously been designated DuP753), group 3 received the converting enzyme inhibitor enalapril, and group 4 received a combination of reserpine, hydralazine, and hydrochlorothiazide. Micropuncture and morphologic studies were performed 10 wk later. Converting enzyme inhibition, AII receptor blockade, and the combination regimen were equally effective in reversing systemic hypertension (time-averaged systolic blood pressure: group 1, 185 +/- 5 mmHg; group 2, 125 +/- 2 mmHg; group 3, 127 +/- 2 mmHg; group 4, 117 +/- 4 mmHg). Micropuncture studies showed that glomerular transcapillary pressure was reduced significantly by converting enzyme inhibition and by AII blockade but not by the combination regimen (delta P: group 1, 49 +/- 1 mmHg; group 2, 42 +/- 1 mmHg; group 3, 40 +/- 2 mmHg, group 4, 47 +/- 1 mmHg). Reduction of systemic blood pressure was associated with the development of markedly less proteinuria and segmental glomerular sclerosis in rats receiving enalapril and MK954 but not in rats receiving the combination regimen (prevalence of glomerular sclerotic lesions: group 1, 41 +/- 4%; group 2, 9 +/- 1%; group 3, 9 +/- 1%; group 4, 33 +/- 6%). These results indicate that the effects of converting enzyme inhibition on remnant glomerular function and structure depend on reduction in AII activity and are not attributable simply to normalization of systemic blood pressure.

Angiotensin II↗
PubMed1991

Glomerular hypertrophy accelerates hypertensive glomerular injury in rats.

Micropuncture and morphological studies were performed in four groups of rats that received subcutaneous infusions of saline or angiotensin II (ANG II) for 8 wk. Group 1 rats received saline; group 2 rats were subjected to uninephrectomy and then received saline; group 3 rats received ANG II (100 ng/min); and group 4 rats were subjected to uninephrectomy and then received ANG II (50 ng/min). In comparison with group 1 rats, group 2 rats exhibited no increase in mean arterial pressure (MAP) (group 2, 102 +/- 6 mmHg; group 1, 104 +/- 10 mmHg) or glomerular capillary pressure (PGC) (group 2, 56 +/- 3 mmHg; group 1, 55 +/- 4 mmHg). In the absence of glomerular hypertension, an increase in glomerular volume (VG) was not associated with glomerular sclerosis in group 2 rats. In contrast to group 2 rats, group 3 rats exhibited increases in MAP (161 +/- 13 mmHg) and PGC (70 +/- 7 mmHg) without any increase in VG. Glomerular hypertension was associated with development of increased albuminuria and glomerular sclerosis in group 3. Group 4 rats exhibited increases in MAP (157 +/- 18 mmHg), PGC (69 +/- 6 mmHg), and VG. These rats also developed glomerular sclerosis and significantly more albuminuria than would have been expected from simple combination of effects of uninephrectomy and ANG II infusion. Additional morphological studies were performed in two groups of rats that received ANG II for 12 wk. Over this period, uninephrectomized group 6 rats infused with ANG II (50 ng/min) developed markedly greater albuminuria and glomerular sclerosis than intact group 5 rats infused with ANG II (100 ng/min).(ABSTRACT TRUNCATED AT 250 WORDS)

Albuminuria↗
PubMed1990

Hypertension and progressive glomerular injury caused by focal glomerular ischemia.

Sprague-Dawley rats received infusions of 55-microns microspheres (groups 1 and 3) or dextrose (groups 2 and 4) into both renal arteries. Groups 1 and 2 rats were studied over 7 mo. In group 1 rats renal embolization increased the mean arterial pressure (group 1, 140 +/- 4 mmHg; group 2, 118 +/- 2 mmHg) without reducing the glomerular filtration rate (GFR; group 1, 4.69 +/- 0.16 ml/min; group 2, 4.57 +/- 0.22 ml/min). Micropuncture studies showed that systemic hypertension was accompanied by an increase in the glomerular capillary pressure of functioning nephrons in group 1 rats. Morphological studies showed that renal embolization caused both glomerular ischemia (group 1, 11.8 +/- 1.9% of glomeruli; group 2, 0.1 +/- 0.1% of glomeruli) and glomerular segmental sclerosis (group 1, 15.0 +/- 1.0% of glomeruli; group 2, 3.3 +/- 0.2% of glomeruli). Groups 3 and 4 rats were studied over 2 mo. Renal embolization again increased the mean arterial pressure without reducing the GFR in group 3 rats. Morphological studies showed that at 2 mo renal embolization caused glomerular ischemia without glomerular segmental sclerosis. These studies show that focal glomerular ischemia can cause systemic and glomerular capillary hypertension in the absence of a reduction in the GFR. They further show that focal glomerular ischemia can cause progressive sclerotic injury in the remaining, nonischemic portion of the glomerular population.

Animals↗
PubMed1990

Angiotensin-converting enzyme inhibitors in the treatment of diabetic glomerulopathy.

Continuous therapy with an angiotensin-converting enzyme (ACE) inhibitor has been shown to have a glomerular vasodepressor effect in the newly diabetic rat and to largely prevent subsequent development of severe sclerosing glomerular injury. Preliminary studies in humans with established diabetic glomerular injury reveal that ACE inhibitor therapy has an antiproteinuric effect and may also slow the decline in glomerular filtration rate that usually attends this disorder. Although promising, the human studies are inconclusive because of short duration and other limitations in experimental technique and study design. Additional trials are required to confirm more positively this amelioration of human diabetic glomerular injury by ACE inhibitor therapy.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1990

Glomerular hypertrophy aggravates epithelial cell injury in nephrotic rats.

Glomerular function and structure were assessed after reduction of nephron number and restriction of protein intake in rats with adriamycin nephrosis. Rats received an injection of adriamycin and were divided into three groups with similar values for albuminuria after 4 wk. Group 1 rats then served as controls, group 2 rats were subjected to four-fifths renal ablation, and group 3 rats were placed on a low protein diet (8% protein) while group 1 and group 2 rats remained on a standard diet (24% protein). Micropuncture and morphometric studies were performed 10 d later. Estimated single-nephron albuminuria (SNalb) was increased by renal ablation in group 2 and decreased by protein restriction in group 3 (group 1, 20 +/- 2 micrograms/d; group 2, 68 +/- 7 micrograms/d; group 3, 12 +/- 1 microgram/d, P less than 0.05 groups 2 and 3 vs. 1). Increased SNalb was associated with increased glomerular volume in group 2 and reduced SNalb was associated with reduced glomerular volume in group 3. (group 1, 1.44 +/- 0.04 x 10(6) microns 3; group 2, 1.66 +/- 0.08 x 10(6) microns 3; group 3, 1.26 +/- 0.03 x 10(6) microns 3, P less than 0.05 groups 2 and 3 vs. 1). Increased SNalb in group 2 was not associated with an increase in glomerular transcapillary hydraulic pressure. The area of epithelial cell detachment from the peripheral capillary wall was markedly increased in group 2 but not perceptibly altered in group 3 (group 1, 16 +/- 5 x 10(2) microns 2; group 2, 65 +/- 17 x 10(2) microns 2; group 3, 18 +/- 5 x 10(2) microns 2; P less than 0.05 group 2 vs. 1). These studies show that glomerular hypertrophy is associated with increased epithelial cell detachment from the peripheral capillary wall and with increased remnant nephron albuminuria after reduction of nephron number in rats with established nephrosis.

Albuminuria↗
PubMed1990

Reversal of glomerular hyperfiltration and renal hypertrophy by blood glucose normalization in diabetic rats.

Two groups of rats with streptozocin-induced diabetes and one group of nondiabetic control rats were studied. Group 1 diabetic rats received daily insulin to maintain blood glucose levels at 300-400 mg/dl for 44 wk. Group 2 diabetic rats received the same insulin regimen for 37 wk and then received an increased dose of insulin to return blood glucose levels close to normal for 7 wk. Group 3 nondiabetic rats were age-matched controls. Glomerular filtration rate (GFR) and kidney weight were elevated in moderately hyperglycemic group 1 rats compared with group 3 rats. Normalization of blood glucose returned both GFR (group 1, 1.83 +/- 0.04 ml/min; group 2, 1.36 +/- 0.05 ml/min; group 3, 1.45 +/- 0.07 ml/min) and kidney weight (group 1, 2.55 +/- 0.06 g; group 2, 1.82 +/- 0.05 g; group 3, 1.72 +/- 0.06 g) to normal in group 2 rats. Despite a sustained increase in GFR, group 1 rats did not exhibit any increase in glomerular volume (group 1, 2.77 +/- 0.09 x 10(6) microns3; group 2, 2.69 +/- 0.09 x 10(6) microns3; group 3, 2.81 +/- 0.7 x 10(6) microns3). Group 1 rats did, however, exhibit a significant increase in glomerular mesangial volume (group 1, 0.31 +/- 0.02 x 10(6) microns3; group 2, 0.28 +/- 0.02 x 10(6) microns3; group 3, 0.21 +/- 0.01 x 10(6) microns3), which was not reversed by normalization of blood glucose in group 2. These findings show that normalization of blood glucose can reverse established glomerular hyperfiltration and renal hypertrophy in moderately hyperglycemic diabetic rats. They further indicate that mesangial expansion is associated with sustained moderate hyperglycemia in this disease model.

Animals↗
PubMed1990

Effects of tissue preparation on glomerular volume and capillary structure in the rat.

The effect of tissue preparation on glomerular volume in normal rats was assessed. In group 1 rats (N = 8), kidney tissue was obtained by immersion-fixation of needle biopsy cores and excised slices from the left kidney and by perfusion-fixation of the remaining right kidney at close to ambient arterial pressure. In group 2 rats (N = 8), tissue was obtained by kidney perfusion at a supernormal pressure (approximately 165 mm Hg). Studies in group 1 showed that mean glomerular volume (VG) was not different in biopsy cores (1.07 +/- 0.13 x 10(6) mu 3) and in kidney slices fixed by immersion (0.92 +/- 0.09 x 10(6) mu 3). A significantly higher value for VG (1.51 +/- 0.18 x 10(6) mu 3) was obtained in kidneys perfusion-fixed at close to ambient arterial pressure. Morphometric studies showed that reduced VG in immersion-fixed tissue was associated with lowered values for peripheral capillary wall surface area (225 +/- 21 x 10(3) mu 2 versus 159 +/- 27 x 10(3) mu 2, p less than 0.05) and reduced mean capillary radius (4.5 +/- 6 mu versus 2.7 +/- 3 mu, p less than 0.05) compared with perfusion-fixed tissue. The data suggest that glomerular capillaries contract when tissue is immersion-fixed and shows that values for mean peripheral capillary wall surface area/glomerulus and mean glomerular capillary radius obtained in immersion- and perfusion-fixed tissue cannot be directly compared. Studies in group 2 showed that VG was not altered by perfusion at a supernormal pressure (1.40 +/- 0.16 x 10(6) mu 3) as compared with perfusion at ambient pressure (1.51 +/- 0.18 x 10(6) mu 3). Further studies in group 1, however, showed that values for VG obtained in paraffin-embedded tissue were approximately 40% lower than values for VG obtained in methacrylate-embedded tissue from the same kidneys.

Animals↗
PubMed1989

Diabetic nephropathy: hemodynamic basis and implications for disease management.

New evidence shows that systemic and intrarenal hemodynamic abnormalities are major factors in the initiation and progression of diabetic nephropathy. Genetic predisposition to elevated systemic blood pressure may contribute to its development. Glomerular vasodilation and hyperfiltration, mediated in part by prostaglandins, may play a role in glomerular damage early in the course of diabetes, but clinical studies are limited. The development of more sensitive assays for albuminuria now allows early diagnosis of incipient nephropathy in the "microalbuminuria" phase. Treatment during this phase with antihypertensive agents, including angiotensin-converting enzyme inhibitors, or with dietary protein restriction, can decrease the degree of albuminuria, but data on their long-term effects on disease progression are limited. In hypertensive patients with established clinical diabetic nephropathy characterized by proteinuria in excess of 0.3 to 0.5 g/d, antihypertensive therapy has a major impact on delaying renal failure. Modalities that lower both systemic and intraglomerular pressure may be more beneficial in preserving renal function than those that primarily lower systemic pressure. Any therapeutic intervention should be monitored meticulously to establish its efficacy and safety in the individual patient. Therapy specifically directed against hemodynamic abnormalities throughout the course of diabetic renal disease may significantly delay and decrease the negative impact of this diabetic complication on survival and quality of life.

Angiotensin II↗
PubMed1989

Angiotensin-converting enzyme inhibitors in the prevention of experimental diabetic glomerulopathy.

Continuous therapy with an angiotensin-converting enzyme (ACE) inhibitor has been shown to have a glomerular vasodepressor effect in the newly diabetic rat and to largely prevent the subsequent development of a severe, sclerosing glomerular injury. Preliminary studies in humans with established diabetic glomerular injury (DGI) reveal that ACE inhibitor therapy has an antiproteinuric effect and may also show the decline in glomerular filtration rate that usually attends this disorder. Although promising, the human studies are inconclusive because of short duration and other limitations in experimental technique and study design. Additional trials are needed to confirm a specific effect of ACE inhibitor therapy to ameliorate human diabetic glomerular injury.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1989

Effect of converting enzyme inhibition on the course of adriamycin-induced nephropathy.

The effect of the converting enzyme inhibitor (CEI) enalapril was assessed in Munich-Wistar rats with established adriamycin nephrosis. Rats were given a single dose of adriamycin and one month later divided into four groups matched for albuminuria, blood pressure, and plasma albumin concentration. Groups 1 and 3 remained untreated while groups 2 and 4 received enalapril. Groups 1 and 2 underwent micropuncture studies after 10 days. These short-term studies showed that enalapril reduced arterial blood pressure (101 +/- 2 vs. 124 +/- 3 mm Hg, group 2 vs. 1, P less than 0.05) and glomerular capillary pressure (54 +/- 1 vs. 61 +/- 2 mm Hg, P less than 0.05) without reducing albuminuria (617 +/- 50 vs. 570 +/- 47 mg/day) or GFR (1.03 +/- 0.04 vs. 1.04 +/- 0.11 ml/min). Groups 3 and 4 were studied at four and at six months to assess the effect of enalapril on progression of renal injury in adriamycin nephrosis. Chronic enalapril treatment reduced blood pressure without reducing albuminuria in group 4. Untreated group 3 rats exhibited a progressive reduction in GFR (0.35 +/- 0.08 ml/min at 4 months, 0.27 +/- 0.07 ml/min at 6 months). Enalapril treatment blunted but did not prevent reduction in GFR in group 4 (0.86 +/- 0.15 ml/min at 4 months, 0.69 +/- 0.13 ml/min at 6 months, both P less than 0.05 vs. group 3). Reduction in GFR was associated with the development of glomerular sclerosis in both treated and untreated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1989

Control of glomerular hypertension by insulin administration in diabetic rats.

Micropuncture studies were performed in Munich Wistar rats made diabetic with streptozotocin and in normal control rats. Diabetic rats received daily ultralente insulin to maintain moderate hyperglycemia (approximately 300 mg/dl). Group 1 diabetic rats studied after routine micropuncture preparation exhibited elevation of the single nephron glomerular filtration rate (SNGFR) due to increases in the glomerular transcapillary hydraulic pressure difference and glomerular plasma flow rate. In group 2 diabetic rats infusion of insulin to achieve acute blood glucose control normalized the glomerular transcapillary pressure gradient while increasing the glomerular ultrafiltration coefficient, so that SNGFR remained elevated. Persistent elevation of SNGFR despite normalization of the transcapillary pressure gradient was also observed in group 3 diabetic rats infused with insulin plus sufficient dextrose to maintain hyperglycemia. These studies indicate that glomerular capillary hypertension in diabetes is an acutely reversible consequence of insulin deficiency and not the result of renal hypertrophy.

Animals↗
PubMed1989

Glomerular hypertrophy and epithelial cell injury modulate progressive glomerulosclerosis in the rat.

The effects of glomerular size and visceral epithelial cell integrity upon the development of progressive glomerulosclerosis was studied by superimposing renal ablation on adriamycin-induced nephropathy in rats. Adriamycin alone caused focal epithelial cell injury and proteinuria but minimal segmental glomerulosclerosis. In normal rats, renal ablation was accompanied by mild progressive proteinuria and glomerulosclerosis. However, renal ablation in rats with adriamycin nephropathy caused a dramatic increase in proteinuria and a disproportionately high frequency of segmental glomerulosclerosis. Accelerated glomerular injury after renal ablation in adriamycin-treated rats was associated with substantial glomerular hypertrophy with near doubling of the tuft volume. Morphometric and autoradiographic studies showed that compensatory glomerular hypertrophy occurs without a proportional increase in the number of visceral epithelial cells, leading to a substantial reduction in the density of these cells within the capillary tuft. The severity of segmental glomerulosclerosis showed a significant correlation with the glomerular volume and the reciprocal of the visceral epithelial cell density. Ultrastructural observations indicate that epithelial defects with detachment of the cell processes from the underlying basement membrane are almost invariably seen in areas of segmental glomerulosclerosis with hyalinosis. These findings suggest that the process of progressive glomerulosclerosis is, to a great extent, contingent upon the development of epithelial cell defects, that result from direct injury or from a reduction in the cell density after inordinate compensatory glomerular hypertrophy.

Analysis of Variance↗
PubMed1988

Plasma protein concentration and colloid osmotic pressure in nephrotic rats.

Colloid osmotic pressure (COP) was related to plasma total protein concentration in rats with adriamycin nephrosis. Nephrotic rats were divided into three groups on the basis of plasma albumin concentration. Measured values for COP were 6 to 8 mm Hg below those predicted by the Landis-Pappenheimer equation in group 3 plasma samples with albumin concentrations 0.5 to 1.0 g/dl. In contrast, measured values for COP were only slightly below those predicted by the Landis-Pappenheimer equation in group 2 plasma samples with albumin concentrations 1.0 to 1.5 g/dl and in group 1 plasma samples with albumin concentrations 1.5 to 2.0 g/dl. The reduction in concentration of albumin was accompanied by an increase in the concentration of non-albumin proteins in each group of nephrotic rats. COP exerted by these non-albumin proteins partially offset the reduction in COP attributable to reduced albumin concentration. Results show that the Landis-Pappenheimer equation significantly overestimates COP only in nephrotic rats whose plasma albumin concentration is very markedly reduced.

Animals↗
PubMed1988

Progressive glomerular injury after limited renal infarction in the rat.

Wistar Munich rats subjected to partial renal ablation were compared with intact rats. Group 1 rats were subjected to bilateral segmental infarction of 40% of their total renal mass. Group 2 rats underwent uninephrectomy. Group 3 rats underwent sham operation. Micropuncture and morphological studies were performed in each group at 28 wk after operation. In group 1, glomerular capillary pressure was elevated by 7 mmHg and systemic blood pressure was elevated by 31 mmHg despite reduction of nephron number by only 40% and reduction of glomerular filtration rate (GFR) by only 10%. Progressive albuminuria and segmental glomerular sclerosis were associated with elevation of glomerular capillary pressure in this group. In group 2, single-nephron glomerular filtration rate (SNGFR) was higher than in group 1, but systemic and glomerular capillary pressure remained normal. Group 2 rats developed markedly less albuminuria and glomerular sclerosis than group 1 rats despite more pronounced remnant nephron hyperfiltration. These studies support the view that glomerular hypertension is the major hemodynamic derangement contributing to remnant glomerular injury and show that capillary hypertension can initiate remnant glomerular injury even when the majority of the renal mass remains intact.

Aging↗
PubMed1988

Increased single-nephron protein excretion after renal ablation in nephrotic rats.

The effects of reducing nephron number in rats with established nephrosis were investigated. Rats received an injection of adriamycin and were divided into three groups with similar values for proteinuria after 4 wk. Group 1 rats were then subjected to sham operation. Group 2 rats were subjected to four-fifths renal ablation, and group 3 rats were subjected to four-fifths renal ablation and then maintained on enalapril. Micropuncture and morphological studies were performed 3 wk later. During this 3-wk period, proteinuria increased slightly in each group. Increased proteinuria in groups 2 and 3 reflected a dramatic increase in remnant nephron proteinuria after renal ablation in nephrotic rats. Increased remnant nephron proteinuria in groups 2 and 3 was associated with increased single-nephron glomerular filtration rate (group 1, 30 +/- 2 nl/min; group 2, 54 +/- 3 nl/min; group 3, 41 +/- 4 nl/min) and increased glomerular volume (group 1, 0.93 +/- 0.05 x 10(6) micron 3; group 2, 1.30 +/- 0.09 x 10(6) micron 3; group 3, 1.27 +/- 0.05 x 10(6) micron 3). The increase in single-nephron glomerular filtration rate after renal ablation in both group 2 and 3 rats was attributable to an increase in glomerular plasma flow (group 1, 119 +/- 14 nl/min; group 2, 217 +/- 18 nl/min; group 3, 183 +/- 13 nl/min) without a significant increase in glomerular transcapillary hydraulic pressure (group 1, 45 +/- 1 mmHg; group 2, 48 +/- 3 mmHg; group 3, 44 +/- 2 mmHg). Group 2 exhibited an increase in systemic blood pressure that was prevented by enalapril treatment in group 3. These studies show that an increase in remnant nephron proteinuria accompanies glomerular hypertrophy and hyperfiltration when nephron number is reduced in nephrotic rats. This increase in remnant nephron proteinuria is not attributable to elevation of systemic or glomerular capillary pressure.

Animals↗