Search PubMed⌕ Search

Biomedical subjects

R D Zipser

Publications and source records attributed to R D Zipser.

At least 55 records · Page 3Linked to original sources
PubMed1983

Stimulation of renal prostaglandins by pressor hormones in man: comparison of prostaglandin E2 and prostacyclin (6 keto prostaglandin F1 alpha).

The effect of vasoconstrictive agonists and their nonpressor analogs on renal prostaglandin production was investigated in normal subjects maintained on constant diets. Arginine vasopressin (AVP), 10 U, desamino-d arginine vasopressin (dDAVP), 4 micrograms, angiotensin II (AII), 5 ng/kg . min, des-Asp angiotensin II (AIII), 5 ng/kg . min, norepinephrine (NE), 0.1 microgram/kg . min, and NE plus phenoxybenzamine (PHB), 0.8 mg/kg, were administered on separate days. Prostaglandin E2 (PGE2) and the stable prostacyclin metabolite, 6 keto prostaglandin F1 alpha were measured in 4-h urine collections by procedures with high resolution chromatography and RIA using highly specific antisera. AVP and dDAVP similarly reduced urine volume and increased urine osmolality. AII, AIII, NE, and NE + PHB did not alter basal urine volume, osmolality, creatinine, or electrolyte excretion. Blood pressure was similarly increased by AII and NE infusions (23 +/- 3 vs. 19 +/- 2 (SE) mm Hg). AVP and AII increased only PGE2 excretion (61 +/- 8 to 151 +/- 34 ng/4 h for AVP, and 38.7 +/- 7 to 75 +/- 19 ng/4 h for AII, P less than 0.05). The nonpressor analogs, dDAVP and AIII, had no effect on urinary prostaglandin excretion. In contrast, NE increased both PGE2 (from 38.7 +/- 7 to 74.5 +/- 12 ng/4 h, P less than 0.02) and 6 keto prostaglandin F1 alpha (from 34.6 +/- 8 to 56.1 +/- 9 ng/4 h, P less than 0.02). alpha-Blockade with PHB totally abolished the NE-induced systemic pressor and prostaglandin stimulatory effect. These data suggest that renal PGE2 and prostacyclin are not altered in parallel by vasoactive stimuli. PGE2 appears to be released in response to agents that induce renal vasoconstriction and reduced renal blood flow whereas renal prostacyclin excretion is stimulated by an adrenergic agonist via alpha-receptor activation and not vasoconstriction per se.

6-Ketoprostaglandin F1 alpha↗
PubMed1983

Plasma corticosteroids in hyperreninemic hypoaldosteronism: evidence for diffuse impairment of the zona glomerulosa.

A subgroup of critically ill patients with selective hypoaldosteronism despite hyperreninemia has recently been defined. The mechanism underlying the subnormal response of aldosterone secretion is poorly understood. As cortisol secretion remains intact and the condition usually follows hypotensive episodes, ischemic or functional impairment restricted to the adrenal glomerulosa may be involved. To evaluate the possibility that a specific biosynthetic pathway deficiency exists in hyperreninemic hypoaldosteronism (HH), basal and ACTH-stimulated levels of aldosterone and its immediate precursors 18-hydroxycorticosterone (18-OHB) and corticosterone (B) were determined in eight HH patients, six critically ill subjects with normal aldosterone responsiveness, and nine healthy subjects. Baseline aldosterone (8.2 +/- 3.2 vs. 44.7 +/- 23.6 ng/dl) and 18-OHB (44.7 +/- 13.6 vs. 547.6 +/- 300.4 ng/dl) were lower in HH patients than in Intensive Care Unit controls (both P less than 0.01) despite similarly increased renin concentration and activity. ACTH-stimulated aldosterone and 18-OHB were significantly lower in HH patients, although the percent increase was similar to Intensive Care Unit controls. Plasma B was also lower in HH patients, though not significantly. After ACTH, B was markedly lower than both ICU controls (1764 +/- 576 vs. 6299 +/- 1266 ng/dl, P less than 0.01) and healthy controls (3261 +/- 248 ng/dl, P less than 0.01). All groups had appropriate cortisol responses demonstrating normal zona fasciculata function. Since 18-OHB arises predominantly from the zona glomerulosa, whereas B also derives in part from the zona fasciculata, the data suggest generalized impairment of the adrenal zona glomerulosa probably affecting both early and late pathway corticosteroid biosynthesis.

18-Hydroxycorticosterone↗
PubMed1983

Association of hypotension with hyperreninemic hypoaldosteronism in the critically ill patient.

Paradoxical suppression of plasma aldosterone (PA) despite increased plasma renin activity (PRA) has recently been noted in some critically ill patients. To determine the prevalence of this entity and to identify possible etiologic factors, we studied 100 consecutive patients admitted to a medical intensive care unit (ICU). Twenty-two of 100 ICU patients had hyperreninemia and inappropriately reduced PA concentrations, with a PA to PRA ratio less than the 98th percentile of the control population. Comparison of clinical data of these 22 patients with the other hyperreninemic ICU patients revealed no differences in electrolyte concentrations, nutrition, medications, or survival. However, persistent hypotension was much more frequent (91% v 53%). Thus, impaired aldosterone response to hyperreninemia has a high prevalence among critically ill patients and may be related to adrenal damage from persistent hypotension.

Acute Disease↗
PubMed1983

Urinary thromboxane B2 and prostaglandin E2 in the hepatorenal syndrome: evidence for increased vasoconstrictor and decreased vasodilator factors.

Vasodilatory prostaglandins function to maintain renal perfusion in patients with cirrhosis and ascites. To evaluate the potential contribution of the vasodilator prostaglandin E2 and the vasoconstrictor metabolite thromboxane B2 to the development of the hepatorenal syndrome, we measured urinary excretion of these products in 14 patients with hepatorenal syndrome and in control populations with acute or chronic liver or kidney failure. Radioimmunoassay measurements were confirmed by bioassay and by mass spectrometry. Prostaglandin E2 was decreased compared with healthy controls (2.2 +/- 0.3 vs. 6.3 +/- 0.8 ng/h, p less than 0.01) and compared with acute renal failure (9.6 +/- 2.1 ng/h) and with alcoholic hepatitis (9.2 +/- 3.3 ng/h). Thromboxane B2 concentration was normal in patients with alcoholic hepatitis (0.12 +/- 0.02 vs. 0.15 +/- 0.03 ng/ml) and minimally increased in acute renal failure (0.18 +/- 0.15 ng/ml), but markedly elevated in hepatorenal syndrome (0.69 +/- 0.15 ng/ml, p less than 0.001). Urinary thromboxane B2 concentration fell with improved renal function in 3 patients who survived. These data suggest an imbalance of vasodilator and vasoconstrictor metabolites of arachidonic acid in patients with the hepatorenal syndrome.

Acute Disease↗
PubMed1982

Urinary excretion of arterial blood prostaglandins and thromboxanes in man.

To determine the fraction of the arterial prostaglandin E2 (PGE2), 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha), and thromboxane B2 (TXB2) that is excreted unmetabolized into human urine, the 3H-labeled compounds were separately infused into the renal artery or brachial vein of 23 subjects. Urine extracts were subjected to sequential chromatography on thin-layer plates, Sephadex LH-20, and reverse-phase high-pressure liquid chromatography to isolate the unmetabolized fraction. Dual isotope ratio techniques were used to identify peak fractions, to assess purity, and to calculate recovery. Following renal artery infusions, 32.2% of 6-keto-PGF1 alpha, 13.5% of TXB2, and 3.9% of PGE2 were excreted unmetabolized. Calculated fractional excretion of these compounds on a single transit through the kidney are approximately 30, 13, and 3.9%, respectively. Following brachial vein infusion of [3H]prostaglandin I2, 2.7% of the infusate was excreted as 6-keto-PGF1 alpha, suggesting that circulating prostaglandin I2 may contribute to urinary 6-keto-PGF1 alpha. When combined with published measurements of urinary PGE2, 6-keto-PGF1 alpha, and TXB2, these data can be used to calculate the maximum arterial blood concentration of these substances. The results indicate that arterial blood concentration of PGE2, TXB2, and 6-keto-PGF1 alpha in man are only a few picograms per milliliter or less.

Adult↗
PubMed1982

Arachidonic acid protection of rat gastric mucosa against ethanol injury.

AA, an essential dietary fatty acid, is a precursor for synthesis of prostaglandins. The ability of prostaglandins to protect the gastric mucosa against ethanol injury prompted us to investigate the possibility of AA providing similar protection in the rat. AA or its solubilizer were instilled intragastrically 60 min prior to absolute ethanol. The gastric lining was examined at 3 and 15 hr after the administration of ethanol. The extent of damage was assessed both macroscopically and histologically. AA administration 30 or 60 min prior to ethanol ingestion protected the gastric mucosa against macroscopic and histological damage for 3 to 15 hr. The intragastric concentration of prostaglandin E2 was 5,000 to 13,000 times higher in the animals pretreated with AA than in the controls. The protective action of AA was markedly diminished by indomethacin pretreatment. Intrajejunal administration of AA did not protect the gastric mucosa. These experiments demonstrate that a dietary constitutent--arachidonic acid--can protect the gastric mucosa against alcohol injury by inducing the synthesis of prostaglandins by the gastric mucosa.

Animals↗
PubMed1981

Studies of the renal vasoactive systems in hyporeninemic hypoaldosteronism.

Plasma renin activity, total renin, active renin, and aldosterone were measured as well as urinary prostaglandin E2 and kallikrein in a group of patients with hyperkalemia (6.1-7.7 mEq per liter) and hyporeninemic hypoaldosteronism. Plasma renin activity and aldosterone were low and the response was markedly blunted to upright posture, and furosemide. The rise in cortisol but not aldosterone was normal following ACTH stimulation. Active renin was depressed; however, total renin was normal. Urine PGE was variable including some low values, but the mean of the group was normal (p greater than 0.1). Urine kallikrein excretion was markedly diminished and undetectable in most cases. Fludrocortisone normalized potassium but minimally increased kallikrein in the patients. The possibility exists that kallikrein deficiency in these patients may underlie the inability to generate active renin.

Adrenocorticotropic Hormone↗
PubMed1981

Stimulation of renal prostaglandin synthesis by the pressor activity of vasopressin.

Renal prostaglandin E2 (PGE2) synthesis is enhanced by exogenous vasopressin (AVP). To determine whether the pressor or the antidiuretic activities of AVP are related to its effect on PGE2 synthesis, AVP and the nonpressor analog, 1-deamino-8-D-arginine vasopressin (dD'AVP), were administered to the isolated perfused rabbit kidney, PGE2 was measured in the renal venous effluent by RIA and validated by bioassay. AVP in doses of 20, 200, and 2,000 ng progressively increased perfusion pressore by 12.1 +/- 2.4, 62.0 +/- 7.9, and 74.3 +/- 13.5 mm Hg, respectively, and increased PGE2 by 28 +/- 7, 80 +/- 3, and 129 +/- 57 ng/50 ml effluent, respectively. Bradykinin and angiotensin II induced a similar dose response on PGE2 release. However, dD'AVP in doses up to 20,000 ng minimally enhanced PGE2 release (20 +/- 16 ng/50 ml) and did not alter perfusion pressure. Simultaneous administration of AVP (200 ng) with the specific AVP pressor antagonist, d-cyclo-O-methyl-tyrosine-AVP, in a 1:10 (agonist to antagonist) weight ratio blunted the increase in perfusion pressure by 59 +/- 9% and blunted the increase in PGE2 release by 59 +/- 10% (P < 0.05). In a 1:100 weight ratio, the pressure antagonist reduced the AVP pressure response by 86 +/- 6% and reduced PGE2 by 84 +/- 7% (P < 0.01). These data suggest that the AVP stimulation of renal PGE2 synthesis is related primarily to its pressor and not to its antidiuretic activity in this in vitro kidney model. (Endocrinology 108: 495, 1981)

Angiotensin II↗
PubMed1981

Dual effects of antidiuretic hormone on urinary prostaglandin E2 excretion in man.

To evaluate the relationship of renal prostaglandin synthesis to urine-concentrating mechanisms, 14 healthy subjects received antidiuretic hormone (ADH) and the nonpressor ADH analog desamino-d-arginine vasopressin (dD'AVP). Endogenous ADH was increased by water deprivation. Urinary prostaglandin E2 (PGE2) was measured by RIA and by bioassay. ADH, dD'AVP, and dehydration each reduced urinary volume by a similar amount (from 582 +/- 66 to an average of 141 +/- 13 ml/4 h) and similarly increased osmolality (from 231 +/- 13 to 721 +/- 31 mosmol/kg). Dehydration and dD'AVP reduced PGE2 from 44 +/- 4 to 25 +/- 5 and 30 +/- 5 ng/4 h, respectively (P less than 0.01), suggesting an inverse correlation of PGE2 with urine osmolality (r = -0.48; P less than 0.005). In contrast, ADH increased urinary PGE2 to 102 +/- 23 ng/4 h (P less than 0.02). Infusions of another vasoconstrictor peptide, angiotensin II, to six of the subjects doubled urine osmolality and also increased urinary PGE2 excretion. These data do not support the theory that the antidiuretic effect of ADH enhances PG synthesis; instead, the data indicate that ADH has two effects on PGE2 excretion: 1) stimulation, presumably by pharmacological pressor activity, and 2) inhibition by antidiuresis.

Adolescent↗
PubMed1981

Hyperreninemic hypoaldosteronism in the critically ill: a new entity.

To define the changes in adrenal gland function during critical illness, we evaluated 28 severely ill patients with persistent hypotension who were hospitalized in a medical intensive care unit. The patients had increased plasma cortisol (mean +/- SE, 40.1 +/- 10.1 micrograms/dl). PRA was increased in all subjects (21.6 +/- 7.2 ng/ml.h); however, the plasma aldosterone concentration was inappropriately low in 18 of the subjects, with values ranging from 1-9 ng/dl, despite normal serum potassium concentrations (4.3 +/- 0.1 meq/liter) and increased concentrations of the aldosterone percursor, 18-hydroxycorticosterone. These 18 patients had hypotension associated with major infections and a high mortality rate (78%). Infusions of ACTH or angiotensin II were associated with a normal aldosterone response in only 2 of the 14 patients tested, also suggesting that the defect was probably at the level of the zone glomerulosa cell. Although infection was a common underlying illness, no other factors, such as dopamine administration, decreased angiotensin-converting enzyme activity, or increased aldosterone clearance, could be implicated as the cause of the phenomena. Thus, selective hypoaldosteronism in the presence of high renin levels exists in a substantial percentage of hypotensive critically ill patients.

Acute Disease↗
PubMed1981

Renal kallikrein excretion in alcoholic cirrhosis. Relationship to other vasoactive systems.

Severe liver disease is often associated with renal hemodynamic changes, and these changes may involve vasoactive hormones. The vasodilatory renal kallikrein-kinin system has received little previous study in these patients. We measured urinary kallikrein in nine patients with alcoholic cirrhosis under rigid metabolic conditions and simultaneously evaluated renin, aldosterone and urinary prostaglandins. Plasma renin and aldosterone were generally increased as expected but urinary kallikrein was surprisingly diminished (13.3 +/- 3.7 vs. 38.8 +/- 11.1 SE, E.U./day, P less than 0.05), despite adequate creatinine clearance (81 +/- 9 ml./min.). Administration of prostaglandin inhibitors reduced urinary prostaglandin E by 72% and creatinine clearance by 56% but did not alter urinary kallikrein. Mineralocorticoid inhibition by spironolactone induced a natriuresis in four patients with ascites (from 1.4-140 mEq.Na+/day) but also failed to alter kallikrein. Thus, kallikrein excretion is paradoxically reduced and seemingly unresponsive to alterations in the prostaglandin and renin-aldosterone systems. If urinary kallikrein quantitatively reflects intrarenal kallikrein-kinin activity, the impairment in this vasodilatory system may mediate the altered renal hemodynamics of severe liver disease.

Adult↗
PubMed1980

Deoxycorticosterone and aldosterone clearance and binding in normal and hypertensive man.

Deoxycorticosterone (DOC) may play a role in several hypertensive disorders in man, but the dynamics of DOC metabolism are unclear. To characterize DOC binding to plasma proteins and its MCR, 12 patients with essential hypertension and 10 age-matched controls were studied. In control subjects, the DOC MCR was nearly identical to the stimultaneously measured aldosterone MCR (719 +/- 32 vs. 734 +/- 61 liters/m2 x day, respectively), and the MCRs of both steroids were not significantly different in essential hypertension (682 +/- 49 and 672 +/- 50 liters/m2 x day, respectively). Whole blood MCR was also unaltered by hypertension. The DOC whole blood MCRs were 1056 +/- 85 and 1040 +/- 69 liters/m2 x day for control and hypertensive subjects, respectively. The aldosterone whole blood MCRs were 916 +/- 96 and 941 +/- 67 liters/m2 x min. The similarity of the DOC MCR to the aldosterone MCR suggested minimal binding of DOC to high affinity carrier proteins, and this was confirmed by equilibrium dialysis with [3H]DOC at 37 C. In plasma, 6 +/- 1% of DOC is unbound, 84 +/- 3% is bound to albumin, and only 10 +/- 4% is bound to nonalbumin proteins. We conclude that the dynamics of DOC closely resemble those of aldosterone, with minimal plasma binding to specific binding proteins and high MCR that are unaltered in essential hypertension.

Adult↗
PubMed1979

Renal prostaglandins and sodium balance in normal man.

We investigated the relationship between urinary prostaglandin E (PGE) excretion and sodium and water balance. PGE excretion was measured in thirteen healthy male volunteers on the metabolic ward during conditions of high sodium (200 mmols/day) and low sodium diets (40 mmols/day) and during intravenous administration of saline and of dextrose and water, using each subject as his own control. PGE excretion was higher on the high sodium than on the low sodium diet (191 +/- 37 SE versus 98 +/- 41 ng/6h, p less than 0.01). Saline and dextrose and water infusions significantly increased PGE excretion while subjects were on low sodium diets (to 314 +/- 74 and 443 +/- 152 ng/6h, respectively, p less than 0.01). While on high sodium diets the increase in PGE excretion during infusions was not significant. To further evaluate the role of prostaglandin in sodium excretion the study was repeated with simultaneous administration of indomethacin or ibuprofen to inhibit prostaglandin synthesis. Sodium excretion from saline and dextrose and water infusions were unaltered. The data suggest that dietary content of sodium may alter PGE excretion, but that acute changes in PGE excretion during saline administration reflect water balance rather than sodium load.

Adult↗
PubMed1979

Prostaglandins: modulators of renal function and pressor resistance in chronic liver disease.

Prostaglandins may modulate renal function and play a role in the hyperreninism and angiotensin pressor resistance of chronic liver disease. To study this possibility, we evaluated 12 patients with alcoholic cirrhosis and ascites. Urine immunoassayable prostaglandin E in 5 female patients was 3.3 +/- 0.5 micrograms/day [normal, 0.3 +/- 0.1 (SE)], renin was 14.6 +/- 3.7 ng/ml.h, and aldosterone was 76 +/- 19 ng/dl. After either indomethacin (200 mg) or ibuprofen (2000 mg) for 1 day, urine immunoassayable prostaglandin E fell to 0.8 +/- 0.4 micrograms/day, renin to 8.0 +/- 2.4 ng/mol.h, and aldosterone to 54 +/- 14 ng/dl (all P less than 0.01). Pressor sensitivity increased dramatically, and creatinine clearance transiently fell from 73 +/- 10 to 32 +/- 7 cc/min (P less than 0.01). Because a primary effect on renin might explain the renal impairment, an additional study used propranolol to lower renin activity. Renal function was unaltered by propranolol. We conclude that prostaglandins play a supportive role in maintaining renal function and are involved in the hyperreninism and pressor resistance of patients with liver disease.

Adult↗
PubMed1979

Adrenocorticotropin-dependent virilizing paraovarian tumors in Nelson's syndrome.

A 35-yr-old woman with Nelson's syndrome presented with amenorrhea and virilization. Serum testosterone (T) concentration was 605 ng/dl and fell to 33 ng/dl when dexamethasone was administered. The MCR of T fell from 1383 to 991 liters/day and the T production rate decreased by 96%. With administration of synthetic ACTH, T concentration rose to 338 ng/dl. Plasma ACTH concentration paralleled T during repeated suppression testing, suggesting that T secretion was dependent on ACTH hypersecretion. Preoperative and intraoperative ovarian vein catheterization suggested that the predominant source of androgen production was from the right ovarian vein. Laporatomy revealed multiple paraovarian tumors in the right mesosalpinyx and mesovarium. Incubation of tumor slices and ovarian tissue with [3H]pregnenolone and [14C]17-hydroxyprogesterone demonstrated conversion of both precursors to T by the tumor and confirmed that the tumors were the source of androgen excess. The microscopic appearance of the tumors closely resembled the morphology of testicular and paratesticular tumors of men with congenital adrenal hyperplasia and Nelson's syndrome. The analogous dependency of the tumors on ACTH hypersecretion in men with paratesticular tumors and in this woman with paraovarian tumors suggests that the tumors may arise in both males and females from a common steroid-secreting cell of adrenogenital origin.

Adrenocorticotropic Hormone↗