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Biomedical subjects

R Zipser

Publications and source records attributed to R Zipser.

18 recordsLinked to original sources
PubMed1987

Mast cell involvement in interstitial cystitis.

A prospective study was designed to examine the relationship of mast cells, and eosinophilic leukocyte density and mediator levels to clinical and histological parameters of interstitial cystitis. Interstitial cystitis and control patients underwent bladder biopsy with histological examination, and quantification of intact and degranulated mast cell and eosinophilic leukocyte density. In addition, bladder tissue histamine content, urinary prostaglandin E2 excretion rates, and serum and urinary major basic protein levels were determined. A strong relationship among detrusor mast cell density, especially degranulated, and degree of epithelial loss, submucosal inflammation, epithelial ulceration, urinary pyuria and response to treatment was noted. Bladder tissue histamine content and urinary prostaglandin E2 excretion were increased in the interstitial cystitis patients. Eosinophil density in bladder biopsies was low uniformly, and interstitial cystitis and control patients showed no statistical difference. In addition, serum and urinary major basic protein levels were below the accepted normal lower limits for this protein. Therefore, our study demonstrates a relationship between the mast cell and the inflammatory process of interstitial cystitis. No similar relationship was noted for the eosinophil.

Biopsy↗
PubMed1985

Role of prostaglandins and angiotensin II in experimental glomerulonephritis.

Moderate autologous nephrotoxic serum nephritis (NSN) in rats causes no reduction in GFR despite a reduction in ultrafiltration coefficient (Kf) to less than one-half of normal. An increase in intraglomerular hydraulic pressure maintains GFR, but the signal and efferent mechanisms for this adaptation remain unknown. Indomethacin and saralasin were used to study the possible roles of prostaglandins and angiotensin II (A-II) in the adaptation to NSN. Indomethacin decreased renal blood flow (RBF) in NSN (-8.6%, P less than 0.001), but not in controls. Renal vascular resistance (RVR) increased in NSN (+ 9.6%, P less than 0.01), but decreased in controls (-5.6%, P less than 0.01). GFR decreased in NSN (-22.3%, P less than 0.01), but increased in controls (+ 10.3%, P less than 0.001). Urinary PGE2 excretion decreased markedly both in NSN and controls. With combined treatment using indomethacin and saralasin, RBF increased in NSN (+ 22.4%, P less than 0.001), but did not change in controls. RVR decreased in NSN (-21.5%, P less than 0.001), but was unchanged in controls. GFR remained unchanged both in NSN and controls. With saralasin alone, RBF increased both in NSN (+ 21.4%, P less than 0.001) and in controls (+ 14.4%, P less than 0.001). RVR decreased both in NSN (-21.8%, P less than 0.001) and controls (-18.7% P less than 0.001). GFR increased (+ 12.3%, P less than 0.05) in NSN, but did not change in controls. Urinary PGE2 excretion was increased in NSN compared to controls, decreased markedly in NSN after either indomethacin or saralasin infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1981

Peptide-induced prostaglandin biosynthesis in the renal-vein-constricted kidney.

The ipsilateral kidney was removed from a rabbit 48h after unilateral partial renal-vein-constriction and was perfused with Krebs-Henseleit media at 37 degrees C. Hourly administration of a fixed dose of bradykinin to the renal-vein-constricted kidney demonstrated a marked time-dependent increase in the release of bioassayable prostaglandin E(2) and thromboxane A(2) into the venous effluent as compared with the response of the contralateral control kidney. The renal-vein-constricted kidney produced up to 60 times more prostaglandin E(2) in response to bradykinin after 6h of perfusion as compared with the contralateral kidney; thromboxane A(2) was not demonstratable in the contralateral kidney. Inhibition of protein synthesis de novo in the perfused renal-vein-constricted kidney with cycloheximide lessened the hormone-stimulated increase in prostaglandin E(2) by 94% and in thromboxane A(2) by 90% at 6h of perfusion. Covalent acetylation of the renal cyclo-oxygenase by prior oral administration of aspirin to the rabbit inhibited initial bradykinin-stimulated prostaglandin E(2) biosynthesis 71% at 1h of perfusion. However, there was total recovery from aspirin in the renal-vein-constricted kidney by 2h of perfusion after bradykinin stimulation. Total cyclo-oxygenase activity as measured by [(14)C]arachidonate metabolism to labelled prostaglandins by renal cortical and renal medullary microsomal fractions prepared from 6h-perfused kidneys demonstrated that renal-vein-constricted kidney-cortical cyclo-oxygenase activity was significantly greater than the contralateral-kidney-cortical conversion, whereas medullary arachidonate metabolism was comparable in both the renal-vein-constricted kidney and contralateral kidney. These data suggest that perfusion of a renal-vein-constricted kidney initiates a time-dependent induction of synthesis of prostaglandin-producing enzymes, which appear to be primarily localized in the renal cortex. The presence of the synthetic capacity to generate very potent vasodilator and vasoconstrictor prostaglandins in the renal cortex suggests that these substances could mediate or modulate changes in renal vascular resistance in pathological states.

Animals↗
PubMed1981

Evidence for a dual action of converting enzyme inhibitor on blood pressure in normal man.

We studied the effect of a converting enzyme inhibitor (CEI), Captopril SQ 14,225 50 mg p.o. in eight supine normal subjects under a high sodium (150 mEq/d) and low sodium (25 mEq/d) diet. On high sodium, plasma renin (PRA) and aldosterone were basal and Saralasin did not lower mean blood pressure. However, CEI induced an 11.4 +/- 3.2 mm fall in blood pressure (p less than 0.02) and either indomethacin 50 mg or ibuprofen 800 mg (PI), when given simultaneously on another day abolished the blood pressure response (2.5 +/- 0.9 mm Hg, p greater than 0.5). In contrast, on a low salt diet where renin was increased, CEI induced a drop in blood pressure which was not significantly altered by PI (12.8 +/- 1.1 vs. 10.0 +/- 3.1 mm Hg, p greater than 0.5). CEI increased plasma renin on both diets (1.7 +/- 0.5 to 3.5 +/- 0.8 and 2.8 +/- 0.6 to 12.5 +/- 3.1 ng/ml/hr respectively both p less than 0.05). Aldosterone did not change (high Na+) or fell (low Na+). Inhibition of Prostaglandin synthesis did not significantly block the renin rise from CEI suggesting that the direct angiotensin II negative feedback is relatively independent of acute prostaglandin release. Our studies suggest that CEI has a dual hypotensive action. In a low renin state, the hypotensive action appears to be mediated through vascular prostaglandins.

Adult↗
PubMed1980

Induction of renin release by exogenous prostaglandins in hyporeninemic hypoaldosteronism.

A deficiency in renal prostaglandin synthesis has been proposed as the cause of the syndrome of hyporeninemic hypoaldosteronism. To determine if renin release could be stimulated by pharmacologic infusions of PGA1, we infused PGA1 0.075 to 0.60 microgram/kg/min to nine patients with the syndrome. Total renal PGE production as measured by urinary PGE excretion was normal (650 +/- 169 vs 400 +/- 55 ng/24hr in normal subjects). Renin (PRA) was markedly depressed in all patients despite stimulation with upright posture and furosemide (1.0 +/- 0.4 vs 9.3 +/- 0.7 ng/ml/hr, p < 0.001). But in two patients PGA1, induced an increase in renin similar to that of normal subjects. PRA increased to a lesser degree in two other patients and plasma aldosterone slightly increased. Five showed no response. Infusions of nitroprusside in doses and duration that mimicked the hypotensive effects of PGA1 failed to increase PRA or aldosterone. The data suggest that total renal PGE production is normal in patients with the syndrome of hyporeninemic hypoaldosteronism. Although orthostasis, furosemide and nitroprusside do not increase renin, prostaglandin A1 infusion appears to be a potent stimulus to renin release in some of the patients.

Aldosterone↗
PubMed1980

Is urinary flow rate a major regulator of prostaglandin E excretion in man?

Urinary PGE2 excretion is enhanced in several polyuric states in man suggesting that PGE2 synthesis could be a mediator of diuresis. To explore the alternate hypothesis that polyuria is the cause of the increased PGE2 excretion, we increased urine flow rate by intravenous administration of dextrose and water with different magnesium, calcium and potassium solutions in four normal males. Urinary PGE excretion rose in parallel with urine volume (r = 0.65 p < 0.01) independently of the electrolyte solution. To determine the effects of chronic alterations in water balance in 5 female subjects, we sequentially regulated oral water intake to induce 1, 2, 4 and 8 liters of urine volume/day. During low (40 mEq) sodium diets, PGE increased from 540 +/- 50 to 4880 +/- 1240 ng/d with increasing urinary volume (r = 0.81, p < 0.01). Similarly, for 200 mEq sodium intake PGE paralleled urinary volume (from 630 +/- 100 to 4740 +/- 800 ng/d, r = 0.61, p < 0.01). In vitro sample dilution studies demonstrated no interference from method blank, and the addition of thin layer chromatography prior to Sephadex chromatography failed to alter assay measurements. We conclude that extreme increases in urinary flow rate may directly enhance PGE excretion in man.

Adult↗
PubMed1980

Contribution of urine volume to the elevated urinary prostaglandin E in Bartter's syndrome and central and nephrogenic diabetes insipidus.

1. Urinary PGE is elevated above normal in patients with Bartter's syndrome, central and nephrogenic diabetes insipidus. 2. K+ loading, Mg2+ infusion, and water-loading-all of which increased urine volume-were associated with augmented urinary PGE in Bartter's syndrome, while fluid restriction decreased urinary PGE to normal. 3. Antidiuresis in central diabetes insipidus with DDAVP, and with indomethacin or ibuprofen in nephrogenic diabetes insipidus, is associated with a decrease in urinary PGE. 4. High urine volume may be a contributing factor to the elevated urinary PGE in Bartter's syndrome, central and nephrogenic diabetes insipidus.

Bartter Syndrome↗
PubMed1978

Prostaglandins: renin release and renal function.

Renal prostaglandins have several potential functions in renal physiology. Perhaps their best documented role is the maintenance of renal blood flow during renal ischemia, although they are apparently not essential to blood flow autoregulation in the absence of ischemia. Alterations in sodium excretion parallel the hemodynamic changes induced by prostaglandin infusions and prostaglandin inhibition with indomethacin. A direct action on sodium balance is unproven. Numerous studies, in vivo and in vitro, have convincingly demonstrated that prostaglandins or their precursors stimulate renin release and prostaglandin inhibition blunts renin release independent of hemodynamic and electrolyte balance. These functions of prostaglandins have implicated them in the manifestations of Bartter's syndrome, the nephropathy of liver cirrhosis, renovascular hypertension, and other nephropathies.

Animals↗
PubMed1978

The measurement of urinary prostaglandin E in normal subjects and in high-renin states.

Antisera generated toward PGE was obtained from rabbits immunized with PGE2 conjugated to bovine thyroglobulin by the carbodiimide reaction. The specificity of the antibody is such that only PGE1 and PGE2 has significant cross-reactions. 13, 14-Dihydro and 15-keto PG's did not react. An RIA capable of measuring 6 pg of PGE2 was developed to measure PGE in human urine. Urine samples adjusted with buffer to pH-5 are extracted with 5% MeOH in CH2CI2 and chromatographed through Sephadex LH-20 columns. The second-antibody technique is used to separate bound from free. This urine method yields blank values of 2 +/- 2 pg per sample, with a between-assay precision determined by duplicate analysis of 14% and intra-assay precision of 8%. The mean urinary excretion rate is 500 +/- 74 (S.E.), +/- 209 (S.D.) ng/day (n = 8) in men and 300 +/- 70, +/- 242 (n = 12) in women. These values are in agreement with those reported by others using gas chromatography-mass spectrometry of receptor assay with hepatic plasma membranes. Patients in a high-renin state, whether normotensive or hypertensive, have elevated PGE in urine. These studies suggest a relationship between the renin-angiotensin system and renal PG's in man.

Antibodies↗
PubMed1977

The effect of sodium restriction and prostaglandin inhibition on the renin-angiotensin system in man.

To investigate the possible interrelationship between the renin-angiotensin and prostaglandin systems, two groups of normal men were evaluated under conditions of varied sodium intake and after indomethacin, an inhibitor of prostaglandin synthesis. Eight subjects were placed on a 200 mEq Na diet and given 45 min infusions of prostaglandin A1 (PGA1) at 0.075 microng/kg/min and angiotensin II at 10 ng/kg/min on separate mornings. PGA1 produced a significant rise in both plasma renin activity (PRA) and aldosterone. Angiotensin II caused a similar rise in aldosterone. The patients were then placed on a 10-20 mEq Na diet and the infusions repeated. PGA1 again induced a further increase in both PRA and aldosterone. Angiotensin II produced the expected increase in aldosterone while PRA decreased. Body weight and 24 h sodium excretion were not different from control days on either diet. When indomethacin was administered to patients on the low sodium diet, PRA fell significantly and there was an increased pressor responsiveness to angiotensin. In a separate group of 4 patients on a low salt intake, basal PRA fell significantly during a 4 day period of indomethacin administration and returned to control values within 48 h after discontinuing the drug. These studies suggest that PGA1 infusions stimulate renin release independently of sodium balance. Inhibition of prostaglandin synthesis lowers PRA and increases pressor responsiveness to angiotensin. The data provide further evidence that vasodepressor prostaglandins may play a role in renin release and blood pressure homeostasis.

Adult↗
PubMed1976

The effect of angiotensin II and indomethacin on immunoreactive prostaglandin "A" levels in man.

The effect of angiotensin II on peripheral levels of immunoreactive prostaglandin A2 (IR-PGA) was determined in 17 normal male volunteers. IR-PGA rose from 338 +/-65 (SE) pg/ml to 635+/-142 in response to pressor infusions of angiotensin II (p less than 0.05 on paired analysis). This increase was not observed when indomethacin, 75 mg p.o., was given to 8 patients two hours prior to a repeat infusion. Five patients of the original group were placed on a low sodium diet (10-20 mEg). The response to angiotensin was now exaggerated (278+/-52 pg/ml to 916+/-284). These five patients were kept on a low sodium intake and given indomethacin 50 mg p.o. g 6 hourly for 4 days. There was no significant rise with angiotensin infusion (106+/-31 pg/ml to 120+/-70). Pressor infusions of angiotensin II raise peripheral levels of IR-PGA, and this response is exaggerated by a low sodium diet and blocked by either acute or chronic indomethacin administration. This data supports the concept that vasodilatory prostaglandins may be released by endogenous angiotensin and thus provide a dynamic antagonism to the renin angiotensin system in man.

Angiotensin II↗
PubMedDate not supplied

Increased excretion of immunoreactive thromboxane B2 in cerebral ischemia.

Thromboxane B2 (TXB2) is the stable metabolite of thromboxane A2 (TXA2), a potent vasoconstrictor which induces irreversible platelet aggregation. The inhibition of TXA2 by aspirin and other agents has been associated with improved outcome following cerebral ischemia in clinical and laboratory studies. To investigate the relation of TXA2 production to cerebral ischemia, we measured the urinary excretion of TXA2 metabolites in 30 patients with acute cerebral ischemia. Urinary immunoreactive TXB2 for this group of ischemic patients was elevated compared to normals, 1818 +/- 344 pg/mg Cr (mean +/- SE) vs 880 +/- 122 pg/mg Cr (p less than .05). Among various subsets of the ischemic patients, those with severe stroke (2108 +/- 536 pg/mg Cr), large vessel disease (1646 +/- 335 pg/mg Cr), and cardiogenic stroke (2712 +/- 1045 pg/mg Cr) were all significantly elevated. Of the stroke patients, only the males demonstrated this significant elevation. These elevations of urinary immunoreactive TXB2 are consistent with a role for increased platelet activation in the pathogenesis of some forms of cerebral ischemia and suggest that gender differences in arachidonate metabolism may exist for stroke patients.

Acute Disease↗