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Biomedical subjects

M Epstein

Publications and source records attributed to M Epstein.

At least 19 recordsLinked to original sources
PubMed1992

Attenuation of endothelin effects by a chloride channel inhibitor, indanyloxyacetic acid.

We have recently proposed that the actions of endothelin (ET) are in part mediated by opening of chloride channels (K. Iijima, L. Lin, A. Nasjletti, and M. S. Goligorsky. Am. J. Physiol. 260 (Cell Physiol. 29: C982-C992, 1991). In the present study the ability of a chloride channel inhibitor, an indanyloxyacetic acid (IAA-94), to block ET-induced effects was examined in cultured vascular smooth muscle cells (VSMC) by spectrofluorometry and direct videomicroscopic visualization of the renal microcirculation in isolated perfused hydronephrotic kidneys (IPHK). A fluorescein isothiocyanate (FITC)-labeled IAA-94 analogue showed specific binding to VSMC. IAA-94 (30 microM) neither affected basal cytosolic calcium concentration ([Ca2+]i) in VSMC nor peak response to ET, but it significantly curtailed sustained elevation of [Ca2+]i (half-time recovery was 147 +/- 23 vs. 248 +/- 33 s in control, P less than 0.05). IAA-94 blunted ET-induced membrane depolarization from 24.5 +/- 3.3 to 8.0 +/- 1.8 mV. In IPHK, ET constricted afferent arterioles (AA) by 29 +/- 2% (18.7 +/- 0.8 to 13.2 +/- 0.6 microns, P less than 0.001). Isradipine reversed this ET-induced vasoconstriction. Pretreatment with IAA-94 did not alter AA diameter, but markedly attenuated ET-induced AA constriction (reduction of AA diameters by only 9 +/- 2%, P less than 0.001). The subsequent addition of isradipine (0.1-1 microM) did not further dilate AA. Our data indicate that IAA-94 markedly attenuates AA vasoconstriction elicited by ET and suggest that ET-induced opening of chloride channels, membrane depolarization, and subsequent activation of voltage-dependent calcium channels contribute to the vasoconstrictor mechanisms of this peptide.

Animals↗
PubMed1992

[Effect of octopamine on arterial pressure and renal function in the normal rat].

Octopamine is a beta hydroxylated phenylethanolamine which accumulates in patients with chronic liver damage. A pathogenic role of octopamine in hemodynamic and systemic alterations of advanced liver failure was investigated in normal awake rats. An infusion of octopamine (220 ug/kg/min) was associated with an increase in mean arterial pressure, urinary volume, urinary Na and K output and their filtration fractions. Glomerular filtration rate and renal plasma flow were not affected. A sudden and marked decrease in mean blood pressure and diuresis was observed after stopping octopamine infusion. Findings during the infusion differ from those observed in the hepatorenal syndrome, although the post infusion period was characterized by hypotension and oliguria. Octopamine behaves as a vasoconstrictor and may interfere with the action of physiologic neurotransmitters.

Animals↗
PubMed1979

Fate of bradykinin-potentiating peptide 9a after intravenous injection.

The fat of less than Glu1-3H-labelled bradykinin-potentiating peptide 9a [BPP9a; less than Glu-Trp-Pro-Arg-Pro-Gln-Ile-Pro-Pro, an inhibitor of angiotensin-converting enzyme (peptidyl dipeptidase)] was studied in the rabbit. After intravenous injection, BPP9a was rapidly removed from blood and much of the associated radioactivity was excreted in urine. Approx. 8% of the radioactivity in urine collected 2h after drug administration occurred in the form of BPP9a itself, the remainder occurring in three lower homologues: less than Glu-Trp (60%), less Glu-Trp-Pro-Arg-Pro-Gln (20%) and less than Glu-Trp-Pro-Arg-Pro-Gln-Ile (12%). Hydrolysis was not accounted for by enzymes in blood or urine. Apparently hydrolysis occurred within the kidney, as less than Gl-Trp was obtained in 60% yield in urine of isolated rat kidney perfused with [less than Glu1-3H]BPP9a.

Animals↗
PubMed1979

Renal 'salt wasting' despite apparently normal renal, adrenal and central nervous system function.

The inability of the kidney to conserve sodium appropriately in response to a restricted sodium intake is reported in a subject who had entirely normal renal and adrenal function and no evidence of central nervous system disease. Subsequent transplantation of his left kidney to his son afforded a unique opportunity to assess renal sodium conservation in each kidney separately: both the patient and his son were unable to achieve balance in response to dietary sodium restriction after transplantation, indicating that the sodium wasting was due to a process intrinsic to both kidneys. The assessment of intrarenal hemodynamics with xenon-133 washout prior to nephrectomy provided insight into the role of intrarenal hemodynamics in the maintenance of sodium homeostasis in man. The xenon washout curve failed to disclose an identifiable second most rapid exponential (CII). This finding, in concert with previous studies demonstrating that diuretic agents with a primary action in the ascending limb of the loop of Henle caused a marked slowing of CII flow, raises the possibility that limited perfusion in the outer medulla of the kidney may be rate-limiting for sodium conservation in man.

Adrenal Glands↗
PubMed1979

A new method of preparing Ca2+-ATPase from sarcoplasmic reticulum: extraction with octylglucoside.

A fast method for preparing Ca2+-ATPase from rabbit muscle sarcoplasmic reticulum was devised. The method involves extracting extrinsic membrane proteins with the non-ionic detergent octylglucoside at high salt concentration. A Ca2+-ATPase of consistently high specific activity (about 25 mumoles/mg.min) is found in the insoluble residue. The method was optimized with respect to the concentrations of detergent and salt, pH, and other extraction conditions. By the criteria of the protein pattern in SDS-polyacrylamide gel electrophoresis, dependence of the hydrolytic activity on the presence of Ca2+, and the phosphoprotein formation, the preparation is identical with the Ca2+-ATPase isolated previously by MacLennan [10] and other authors. The main advantages of the new method are its rapidity, its reliability, and the high specific activity of the purified enzyme.

Animals↗
PubMed1979

Long-term analysis of cerebrospinal fluid shunt infections. A 25-year experience.

The authors have retrospectively analyzed 840 cerebrospinal fluid shunting procedures over a 25-year period to determine the relationships between infection rates and several possible influences on infection. Two-thirds of all shunt infections occurred within 1 month of surgery. The very young and very old had higher infection rates. Infections became less prevalent over the period of the study, and mortality from infection decreased from 35% to 6%. Successive shunts (revisions) were found to have progressively higher infection rates. Ventriculoatrial and ventriculoperitoneal silicone plastic shunts had similar infection rates (11.4% and 12.0%). The uncontrolled use of prophylactic antibiotics had no effect on shunt infections. Staphylococcus epidermidis became gradually more prevalent over the period of the study, and eventually caused one-half of all infections. Where infection occurred in the presence of prophylaxis, the infectious organism was usually sensitive to the antibiotic being used. The surgeon was found to be the largest single factor in the incidence of shunt infections. A 25-fold variance in infection rates among surgeons could be related to individual experience and technique.

Adolescent↗
PubMed1979

Effects of aging on the kidney.

A host of abnormalities of renal structure and function accompany advancing age. This presentation briefly surveys the renal anatomical and functional changes associated with senescence. Four areas of renal functional change have been selected for in-depth discussion: a) renal blood flow; b) glomerular filtration rate; c) renal sodium handling; and d) renal concentrating ability. The methodologic considerations including population selection which confound the assessment of the effects of aging on renal function are discussed. In addition, the functional changes associated with senescence are discussed in the context of longitudinal studies and studies utilizing appropriate patient cohorts, including potential kidney transplant donors. The clinical implications of senescent changes with regard to adjusting "normative" standards to fit the age of the patient are addressed. Furthermore, the implications of age-related renal functional alterations in predisposing the elderly patient to a number of fluid and electrolyte derangements are considered.--Epstein, M. Effects of aging on the kidney.

Adult↗
PubMed1978

Reconstitution of carbamylcholine-dependent sodium ion flux and desensitization of the acetylcholine receptor from Torpedo californica.

Membranes rich in acetylcholine receptor were isolated from Torpedo californica by a modification of the procedure of Sobel et al. (Sobel, A., Weber, M., and Changeux, J.-P. (1977) Eur. J. Biochem. 80, 215-224). The receptor was extracted with 2% potassium cholate in the presence of 2.5% soybean phospholipids. After reconstitution by the cholate dialysis procedure, the vesicles exhibited a rapid, carbamylcholine-dependent uptake of 22Na+, which was inhibited by alpha-bungarotoxin and several other known inhibitors. At concentrations above 5 x 10(-5) M carbamylcholine, the fast phase of Na+ influx lasted less than 10 sec. At 5 x 10(-6)M, it lasted 30 sec but was only about 50% of the maximal total uptake observed at optimal agonist concentration. The phenomenon of desensitization was exhibited by the reconstituted vesicles. When 2 x 10(-4)M carbamylcholine was added, 15 sec before 22Na+, the rapid Na+ influx phase was no longer observed.

Acetylcholine↗
PubMed1978

Metabolism of arginine by the isolated perfused rat kidney.

In order to evaluate the renal contribution to the metabolism of arginine, we have evaluated its biosynthesis and catabolism in the isolated perfused rat kidney. The kidneys of eight male Sprague-Dawley rats were perfused with Krebs-Ringer-bicarbonate buffer containing albumin and amino acids. Twenty-five muCi of L-[guanidino-14C]arginine or 25 muCi L-[guanidino-14C]citrulline were added to the system and radiochromatograms of the perfusate were obtained at 0, 30, 60, and 90 min. Perfusate levels of urea, creatine, and guanidine derivatives were measured with high-pressure liquid chromatography. During perfusion there was net utilization of arginine and net production of creatine, guanidinoacetic acid (GAA) and guanidinosuccinic acid (GSA). The guanidino carbon of arginine was incorporated by the kidney into urea, creatine GSA, GAA, and guanidinobutyric acid. The production of 14C-labeled urea from L-[guanidino-14C]citrulline was substantially lower than that previously demonstrated in the liver, while that of arginine was approximately 20 times greater. These studies demonstrate the important contribution of the kidney to the synthesis and metabolism of arginine.

Acetates↗