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Biomedical subjects

N Bank

Publications and source records attributed to N Bank.

At least 37 records · Page 2Linked to original sources
PubMed1989

Proximal bicarbonate absorption independent of Na+-H+ exchange: effect of bicarbonate load.

To study proximal tubule bicarbonate absorption that is not due to the neutral Na+-H+ antiporter, mid to late proximal convolutions of the rat kidney were microperfused in vivo with a sodium-free choline solution containing 10(-3) M amiloride. The average sodium concentration resulting from sodium influx was 12 mM. At such low intraluminal [Na+], 10(-3) M amiloride should have inhibited the Na+-H+ antiporter by greater than 95%. When 25 mM HCO3- was in the perfusion fluid, measured total CO2 absorption was 100 pmol.mm-1.min-1. When luminal [HCO3-] was raised to 50 mM, and blood [HCO3-] was also raised to approximately 50 mM to avoid a transepithelial HCO3- concentration gradient, total CO2 absorption increased to greater than 300 pmol.mm-1.min-1. Thus raising intraluminal HCO3- concentration caused a marked increase in total CO2 absorption even though intraluminal [Na+] was low and amiloride was present. Control perfusions containing 140 mM Na+ yielded total CO2 absorption that was approximately 100 pmol.mm-1.min-1 higher than with the respective sodium-free perfusion solutions. In additional experiments, either DCCD or NEM was added to sodium-free perfusion solutions to inhibit H+-ATPase. These inhibitors reduced Na+-H+ independent total CO2 absorption markedly. Our observations suggest that under physiological acid-base conditions, sodium-independent H+ secretion can account for approximately 50% of total HCO3- absorption in mid to late proximal convolutions. This mechanism is stimulated by an increase in ambient HCO(-3) concentration to a degree that might account for the load-dependency of proximal HCO(-3) absorption in these segments of the proximal tubule.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Sorbinil prevents glomerular hyperperfusion in diabetic rats.

The role of polyol pathway metabolism in glomerular hyperperfusion of insulin-dependent diabetes mellitus (IDDM) was studied in rats. Streptozotocin-induced diabetic rats were fed the aldose reductase inhibitor, sorbinil (8 mg/day). Untreated diabetic rats and normal rats served as controls. All groups were fed the same diet, rationed to 20 g/day. Micropuncture, plasma renin activity (PRA), and glomerular angiotensin II (ANG II)-receptor measurements were made 7-15 days after streptozotocin injection. Untreated diabetic rats had higher than normal single-nephron filtration rate (SNGFR), plasma flow (QA), and blood flow (SNBF), and reduced afferent resistance. Glomerular ANG II-receptor sites were markedly decreased. In diabetic rats fed sorbinil SNGFR, QA, and SNBF were all lower than in untreated diabetic rats, and indistinguishable from values in normal rats. However, single-nephron filtration fraction (SNFF) rose above normal. PRA, glomerular ANG II receptors, and blood glucose were not affected by sorbinil. In normal rats fed sorbinil, SNGFR, QA, and SNBF were not significantly different than in normal rats. Our observations are consistent with the view that polyol pathway metabolism plays a role in glomerular hyperperfusion in IDDM. Inhibition of aldose reductase increased vascular smooth muscle tone at pre- and probably postglomerular sites.

Aldehyde Reductase↗
PubMed1989

Galactose feeding causes glomerular hyperperfusion: prevention by aldose reductase inhibition.

Experimental dietary galactosemia is known to result in accumulation of the polyol, galactitol, via the aldose reductase metabolic pathway in a variety of tissues, including renal glomeruli. Because increased polyol accumulation also occurs in insulin-dependent diabetes mellitus (IDDM), in which marked renal glomerular hyperperfusion occurs, we have studied glomerular hemodynamics in rats with experimental galactosemia. Insulin deficiency and its accompanying metabolic disorders are not present in this experimental model. In additional groups of animals, aldose reductase inhibitors, either sorbinil or tolrestat, were added to the galactose diet. In all, five groups of rats were studied: regular diet, 50% galactose diet, regular diet plus sorbinil, 50% galactose diet plus sorbinil, and 50% galactose plus tolrestat. The diets were comparable in protein and salt, and the rats were pair fed. Micropuncture and whole kidney clearance measurements were carried out after 10-14 days on these diets. Compared with rats fed the regular diet, those fed with 50% galactose diet had significantly higher glomerular filtration rates, renal plasma flow, single-nephron glomerular filtration rates, and plasma flow (QA), whereas afferent vascular resistance (RA) was decreased. Addition of sorbinil or tolrestat to the high-galactose diet not only prevented renal hyperperfusion but RA and single-nephron filtration fraction (SNFF) were higher than in normal rats, and QA was lower. In addition, sorbinil administration to rats on the control diet caused significant decreases in single-nephron blood flow and the ultrafiltration coefficient and a rise in SNFF.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldehyde Reductase↗
PubMed1988

Effects of dietary electrolyte supplementation on gentamicin nephrotoxicity.

The effects of electrolyte supplementation via drinking solutions on gentamicin-induced nephrotoxicity were studied in rats. Four groups of animals were injected with gentamicin, 120 mg/kg daily for 5 days and were studied 2-4 days after the last injection. Electrolyte supplements were begun before the gentamicin injections and were continued throughout the study. The drinking solutions were tap water, NaCl, NaCl + KCl, or NaHCO3 + KHCO3 + diamox. At the end of the study, blood urea nitrogen (BUN) and serum creatinine were markedly increased only in the group receiving tap water. Nevertheless, 24 hour creatinine clearance in awake rats and inulin clearance in anesthetized rats were found to be severely reduced in all gentamicin-treated animals. However, the rats receiving NaHCO3 + KHCO3 + diamox had significantly higher creatinine clearance than all other experimental groups. Proximal intratubular free-flow pressure, measured by micropuncture, and internal proximal diameters were significantly increased above normal controls in all groups, but were least abnormal in the rats receiving HCO3- and diamox. Semiquantitative histologic evaluation revealed significantly less tubular necrosis and cast formation in this group than in all the other experimental groups. The observations suggest that dietary sodium, potassium, and chloride supplements, even accompanied by large fluid intake, provide relatively little protection against gentamicin nephrotoxicity. In contrast, HCO3- and diamox supplements resulted in significant, albeit incomplete, protection of GFR and renal histology.

Animals↗
PubMed1988

Vasoregulatory hormones and the hyperfiltration of diabetes.

The role of renal vasoregulatory hormones in the hyperfiltration of early insulin-dependent diabetes mellitus (IDDM) was studied by micropuncture methods in rats with streptozotocin-induced diabetes. Seven to ten days after streptozotocin injection, untreated diabetic rats had elevated glomerular filtration rate (GFR) and single-nephron glomerular filtration rate (SNGFR), compared with normal euvolemic rats. Infusion of indomethacin (5 mg/kg) markedly reduced urinary and proximal tubular fluid prostaglandin E2 (PGE2), but GFR and SNGFR did not change. In a second group, intrarenal infusion of aprotinin (1,000 kallikrein inhibitor units.min-1.kg-1) to inhibit kallikrein also had no effect on GFR or SNGFR. In a third group, intrarenal infusion of angiotensin II (ANG II, 0.1 microgram.min-1.kg-1) reduced GFR, renal plasma flow (RPF), SNGFR, and glomerular plasma flow rate (QA) to values close to those in normal euvolemic rats. Single-nephron filtration fraction rose significantly with ANG II, but glomerular pressure (PG) was unaltered. Tubular fluid PGE2 increased in response to ANG II. Saralasin infusion following ANG II returned GFR, RPF, SNGFR, and QA to supernormal levels, and PG fell. In chronically salt-loaded normal rats, the responses to intrarenal ANG II and saralasin were similar to those observed in the diabetic rats. We conclude that hyperfiltration in early IDDM is not dependent on intact renal PGE2 or bradykinin synthesis. The results with ANG II infusion indicate that pre- and postglomerular and glomerular contractile cells of the diabetic kidney are able to constrict in response to this hormone.

Algorithms↗
PubMed1988

Sodium restriction corrects hyperfiltration of diabetes.

The effect of a low-sodium diet on the abnormal glomerular hemodynamics of early diabetes was studied in rats. Starting 5 to 7 days after onset of streptozotocin-induced insulin-dependent diabetes mellitus (IDDM), rats were fed a low-sodium diet for 4-5 days. Normal rats fed the same diet served as controls. Micropuncture measurements were made during a control period, followed by a second period when saralasin was infused into the left renal artery. During the first period, single-nephron glomerular rate (SNGFR), glomerular plasma flow (QA), glomerular blood flow (SNBF), filtration fraction (SNFF), and glomerular hydraulic pressure (PG) in the diabetic rats were not significantly different from the normal controls. Saralasin infusion resulted in striking increases in SNGFR, QA, SNBF, and Kf, and significant decreases in SNFF, PG, and delta P. The responses to saralasin imply that the low-sodium diet resulted in ANG II-mediated vascular constriction at pre- and postglomerular sites, and probably the glomerular mesangial cells as well. Our observations suggest that the abnormally elevated glomerular blood flow and filtration rate of early IDDM can be corrected by a low-sodium diet via stimulation of endogenous ANG II.

Algorithms↗
PubMed1987

Evidence against increased glomerular pressure initiating diabetic nephropathy.

Studies were carried out to determine whether exaggerated glomerular hydraulic pressure (PG) initiates the development of glomerular pathology and proteinuria in insulin-dependent diabetic rats. Normotensive (WKY) and hypertensive rats (SHR) were made diabetic by streptozotocin injection. One group of SHR diabetic rats was treated with antihypertensive drugs to reduce blood pressure. One week after onset of diabetes, micropuncture determinations of PG, measured by stopped-flow technique, revealed that PG was higher in WKY diabetics than in non-diabetic WKY controls, and that PG was even higher in SHR diabetics (P less than 0.05). Similarly prepared groups of animals were followed for six months, approximately one fifth to one third of the expected life span of these rats. Tail systolic blood-pressure measurements documented continuous severe systolic-hypertension in SHR diabetics, normal pressure in the WKY diabetics and hypotension in the SHR diabetics treated continuously with antihypertensive drugs. Urinary protein excretion, measured monthly, was statistically the same in all groups, with no evidence of a progressive rise in the SHR diabetics. PG measured in two rats from each group after four months of diabetes was similar to values found after one week of diabetes. Semiquantitative histologic scoring of glomerular mesangial expansion after six months of diabetes failed to demonstrate any significant difference between the normotensive WKY diabetics and the hypertensive SHR diabetics. These observations suggest that elevated PG does not in itself initiate glomerular pathology or proteinuria in diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Acute effect of calcium and insulin on hyperfiltration of early diabetes.

We examined the effect of calcium administration on renal hyperfiltration in streptozotocin-treated diabetic rats. Rats were studied 7-10 days after streptozotocin injection. Intrarenal infusion of CaSO4 in Ringer's solution had no effect on the hyperfiltration of the diabetic kidney. Infusion of insulin in a dose that did not effect hyperglycemia also had no effect on the hyperfiltration. However, when insulin and calcium were infused together, a rapid decrease in glomerular filtration rate, single-nephron filtration rate, glomerular hydraulic pressure, and renal plasma flow occurred. The contralateral control kidney was unaffected. Verapamil infusion had no significant effect in untreated diabetic rats, but immediately reversed the vasoconstriction induced by insulin plus calcium. Similar intrarenal insulin and calcium infusions had no effect in euvolemic or chronically salt-loaded nondiabetic rats. The observations indicate that renal vascular cells (probably preglomerular) are hyperresponsive to calcium in early insulin-dependent diabetes mellitus and that this response requires insulin. We suggest that decreased renal vascular tone in early insulin-dependent diabetes mellitus may be due in part to defective transmembrane calcium flux across vascular smooth muscle cells. Insulin appears to be required for calcium entry or mobilization, to initiate renal vascular smooth muscle contraction in diabetes.

Animals↗
PubMed1987

In vivo demonstration of glomerular PGE2 responses to physiological manipulations and experimental agents.

Experiments were carried out in rats to determine whether prostaglandin E2 (PGE2) synthesized in vivo by individual glomeruli could be measured in fluid obtained from early proximal tubule convolutions. A newly developed nonradioactive enzyme-linked immunoassay for PGE2, capable of measuring 0.1- to 0.25-pg quantities, made this approach feasible. In salt-deprived rats, recollection micropuncture samples were obtained from the earliest proximal convolution [tubular fluid-to-plasma insulin ratio (TF/PIn) 1.13] for measurement of PGE2, and then single-nephron glomerular filtration rate (SNGFR). PGE2 was also measured in serum ultrafiltrate, and theoretical maximum "filtered" PGE2 was calculated for each nephron. This was compared with the measured PGE2 from the same nephron. Indomethacin was then given to inhibit cyclooxygenase. We found that measured PGE2 in early proximal fluid (TF) was higher than could be attributed to glomerular filtration. Indomethacin markedly decreased measured PGE2 in early TF. Administration of probenecid, to block tubular transport of PGE2, did not alter the observations. In chronically salt-loaded rats early TF PGE2 was significantly less compared with the salt-deprived rats. Intrarenal infusion of a nonpressor dose of angiotensin II (ANG II) doubled PGE2 appearance in early TF samples. We conclude from these observations that PGE2 in early TF is derived in part from the glomerulus. In the intact rat, glomerular PGE2 synthesis is higher after salt deprivation than after salt loading, inhibited by indomethacin, and stimulated by ANG II. This new approach will allow evaluation of the role of in vivo glomerular PGE2 production in various pathophysiological conditions.

Angiotensin II↗
PubMed1986

Microperfusion study of proximal tubule bicarbonate transport in maleic acid-induced renal tubular acidosis.

Microperfusion studies were carried out in rats to examine the abnormality in proximal tubule HCO3- transport caused by maleic acid administration. Permeability of the proximal tubule to HCO-3 was measured by perfusing proximal tubules with a HCO3- -free low-buffer isotonic equilibrium solution containing acetazolamide after plasma [HCO3-] had been raised by intravenous NaHCO3 infusion. Insulin recovery in the collected perfusate was approximately 100% in control and maleic acid-treated rats. CO2 influx measured by microcalorimetry was not significantly different in control vs. maleic acid-treated rats. Thus maleic acid did not cause increased permeability of the proximal tubule to either inulin or HCO3-. In a second group of experiments, proximal tubule fluid and HCO3- efflux were measured in paired-reperfusion experiments before and after maleic acid administration. The perfusion fluid contained 25 mM HCO3- and 120 mM Cl-. HCO3- absorption was inhibited 25% (79 pmol/min), Na+ was inhibited 22% (164 pmol/min), and Cl- absorption (calculated as the anion gap) by 85 pmol/min. [HCO3-] in the collected perfusate rose significantly after maleic acid, presumably accompanied by a fall in [Cl-]. The observations indicate that proximal renal tubular acidosis (RTA) induced by maleic acid is characterized by impaired lumen-to-blood transport of sodium bicarbonate and chloride but not by increased backflux. Based on previously demonstrated effects of maleic acid on mitochondrial energy metabolism and cellular ATP levels, we postulate that the principal transport abnormality is impaired basolateral membrane active sodium transport, leading to a secondary reduction in brush border Na+-H+ exchange.(ABSTRACT TRUNCATED AT 250 WORDS)

Acidosis, Renal Tubular↗
PubMed1985

Evidence for a DCCD-sensitive component of proximal bicarbonate reabsorption.

To examine the possible contribution of active H+ secretion mediated by brush border enzymes to proximal tubule HCO-3 absorption, paired reperfusions of surface proximal convoluted tubules were performed with the inhibitor dicyclohexylcarbodiimide (DCCD). In control studies using a solution devoid of HCO-3 but containing 5.5 mM glucose, 1 mM DCCD had no effect on glucose or fluid (Na+) absorption, suggesting that this inhibitor did not interfere with sodium entry at the brush border or mitochondrial energy production (ATP synthesis). In experiments using a perfusion solution containing 18-25 mM HCO-3, DCCD caused a fall in absolute CO2 absorption of approximately 15% under eucapneic conditions and 30% during acute hypercapnia. One millimole per liter amiloride (an inhibitor of the passive Na+-H+ exchanger) caused a 15% inhibition of CO2 absorption during acute hypercapnia and a disproportionately large reduction in fluid (Na+) absorption. The latter was not due to cell poisoning, since 1 mM amiloride had no inhibitory effect on fluid or glucose absorption when a HCO-3-free perfusion solution was used. Addition of 1 mM DCCD to a perfusion solution containing either 10(-3) M amiloride or 10(-4) M acetazolamide caused a significant inhibition of CO2 absorption compared with amiloride or acetazolamide alone. The observations are consistent with the view that in addition to passive Na+-H+ exchange, active transport mediated by either a H+-ATPase or a redox-driven H+ pump in the brush border contributes significantly to HCO-3 absorption in the proximal tubule.

Absorption↗
PubMed1984

Comparison of long-term renal hemodynamic effects of methyldopa and propranolol in patients with hypertension and renal insufficiency.

Studies were carried out in 15 patients with renal insufficiency and hypertension to compare the long-term effects of methyldopa and propranolol on renal hemodynamics. Inulin and PAH clearance measurements were made under baseline conditions and four to six months of antihypertensive therapy with each of the two drugs. Eight of the 15 patients (group I) were started on methyldopa and then switched to propranolol; and in the other seven (group II), the sequence was reversed. There were no statistical differences in blood pressure or inulin or PAH clearances under baseline conditions between the two groups of patients. Blood pressure was controlled equally with the two drugs in combination with furosemide. In group I, there was no significant effect of either antihypertensive drug on inulin clearance, but PAH clearance was significantly higher during methyldopa than propranolol therapy. In group II, the same higher PAH clearance was found with methyldopa, even though the sequence of drug administration was opposite to that of group I. Challenge with iv furosemide resulted in a greater 3-hour natriuresis during methyldopa than propranolol treatment. The observations indicate that glomerular filtration rate (GFR) is not significantly affected by long-term treatment with methyldopa or propranolol but that renal plasma flow (RPF) is higher during treatment with methyldopa in patients with renal insufficiency and hypertension. The higher RPF apparently enhances the acute natriuretic effect of iv furosemide.

Adult↗
PubMed1984

Failure of changes in intracapillary pressures to alter proximal fluid reabsorption.

To determine the role that peritubular capillary oncotic and hydraulic pressures play in regulating urinary sodium excretion in the euvolemic state, experiments were carried out in rats under conditions which altered these pressures without volume expanding the animal. In cross-circulation experiments, the donor rat was expanded with plasma or Ringer's solution while the recipient rat remained euvolemic. Micropuncture measurements in the euvolemic recipients demonstrated significant increases in efferent plasma flow rate (QEA), capillary hydraulic pressure (Pc), and decreases in mean capillary oncotic pressure (pi c). There were no changes in nephron GFR (SNGFR), absolute proximal reabsorption (APR), or UNaV. In additional studies, peritubular oncotic pressure was lowered markedly by plasmapheresis of the experimental animal. Large decreases in pi c were produced without any change occurring in SNGFR, APR, or UNaV. Measurements of interstitial hydraulic pressure (Pi) with a subcapsular pressure pipet revealed that Pi was unaltered under all of these conditions but rose markedly in rats undergoing a saline-expansion diuresis. Our findings indicate that APR and UNaV can remain constant despite large changes in pi c, Pc, and QEA in nonexpanded animals. Furthermore, the changes in pi c, Pc, and QEA induced in the euvolemic non-diuretic rats were the same as those in the saline-expanded diuretic rats. We conclude that under euvolemic experimental conditions, urinary sodium excretion and APR do not correlate with intracapillary pressures or flow rates in the renal cortex. The only difference found between the nondiuretic and diuretic rats was a rise in Pi in the latter group.

Animals↗
PubMed1984

Increased peritoneal permeability in rats with alloxan-induced diabetes mellitus.

Increased capillary permeability to small and large molecules has been demonstrated in several organs of human diabetics and in animal models of the disease. To assess the effects of diabetic microangiopathy on peritoneal clearances, peritoneal dialysis was performed in normal rats, rats with gentamicin-induced acute renal failure, and rats with mild and severe alloxan-induced diabetes mellitus. Peritoneal clearances of urea, inulin, and albumin were significantly increased in the severely diabetic rats compared with other groups. Microscopic examination revealed abnormally small adipose cells in the peritoneums of the severely diabetic rats, associated with a generally malnourished appearance. Vascular abnormalities attributable to diabetes mellitus, such as capillary basement membrane layering and neovascularization, were demonstrated in the peritoneums+ of both mildly and severely diabetic rats, though not to a greater extent in either group. We conclude that, as in many other parts of the body, peritoneal permeability to small, middle and large molecules is increased in early, severe, untreated diabetes mellitus.

Acute Kidney Injury↗
PubMed1983

Triad of glomerulonephritis, antinuclear antibodies, and positive skin immunofluorescence. Variant of systemic lupus erythematosus.

We are reporting findings in 13 patients who presented with glomerulonephritis without evidence of systemic disease, but who were found to have positive antinuclear antibody results and immunoglobulin and/or complement deposits at the dermal-epidermal junction of normal skin not exposed to light. There was no evidence of other organ involvement, and serologic tests for systemic lupus erythematosus (SLE) gave negative results. The renal disease is characterized by severe proteinuria, focal or diffuse proliferative glomerular lesions on biopsy, with variable patterns of immunoglobulin deposits. No clinical manifestations or serologic results typical of SLE have developed during prolonged observation. HLA phenotyping carried out in eight of the 13 patients revealed DR2 or DR3 alloantigens or both in seven of the eight patients, an incidence similar to that in patients with overt SLE. Because of the specificity of the skin biopsy immunofluorescence, the similarity of HLA-DR antigens, and a favorable response of the renal disease to therapy, we believe that these patients have a variant of SLE.

Adolescent↗