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Biomedical subjects

E J Zambraski

Publications and source records attributed to E J Zambraski.

At least 37 records · Page 2Linked to original sources
PubMed1986

Renal prostaglandin E2 and F2 alpha synthesis during exercise: effects of indomethacin and sulindac.

To assess the effects of acute exercise on renal prostaglandins E2 (PGE2) and F2 alpha (PGF2 alpha) synthesis, urine collections were obtained from six women before and after 30 min of treadmill exercise at approximately 80% of their maximal oxygen consumption. After receiving a placebo for 3 days, with acute exercise, there was a significant increase only in recovery urine PGE2 concentration. Due to a decline in urine volume, PGF2 excretion was unchanged and PGF2 alpha excretion was significantly decreased by exercise. Subjects repeated the tests after 3 d of indomethacin treatment (150 mg X d-1), a known renal prostaglandin (PG) inhibitor, and 3 d of sulindac (300 mg X d-1), a non-steroidal anti-inflammatory drug which may not inhibit renal PG synthesis. Pre-exercise urine PGE2 concentrations were decreased by indomethacin but not by sulindac, whereas, PGF2 alpha concentrations were decreased by both drugs. When compared to the control test, indomethacin and sulindac had different effects on pre-exercise urine/plasma osmolality ratios and free water clearances. Neither indomethacin nor sulindac influenced the decreases in free water clearances, which were observed during the placebo tests. Exercise proteinuria was significantly increased by indomethacin but not by sulindac. In conclusion, these data demonstrate that acute exercise may stimulate renal PGE2 synthesis. During exercise, renal PG synthesis attenuates protein excretion. There also appear to be differences between indomethacin and sulindac with regard to the effects on renal PG synthesis and kidney function.

Adult↗
PubMed1985

Adrenocortical function in deoxycorticosterone acetate (DOCA)-hypertensive Yucatan miniature swine.

Adrenocortical function was assessed in six normal and six chronic (greater than 12 weeks), DOCA-hypertensive Yucatan miniature swine; mean arterial pressures were 115.3 +/- 11.7 and 163.6 +/- 27.2 mm Hg, respectively (mean +/- SEM). Adrenocortical function was evaluated in vivo by measuring changes in plasma cortisol and aldosterone in response to exogenous ACTH (0.25 mg, iv), and in vitro by measuring the responses of collagenase-isolated adrenocortical cells to ACTH and angiotensin II. Corticoids were measured by specific radioimmunoassay. Basal plasma cortisol values of conscious DOCA-hypertensive swine were approximately 53% of the values of normotensive swine (P less than 0.05). However, ACTH induced a 419% increase in plasma cortisol values in DOCA-hypertensive swine compared to a 261% increase in the normotensive swine (P less than 0.05). These differences between the two groups were not altered by anesthesia. There were no significant differences in ACTH-induced changes in plasma aldosterone between the normotensive and DOCA-hypertensive swine. Experiments in vitro showed that the corticoid secretory responses of adrenocortical cells from DOCA-hypertensive animals were 6 times more sensitive to ACTH and 3.2 times more sensitive to angiotensin II than those of cells from normotensive swine. Thus, despite the possibility of adrenocortical insufficiency due to suppressed plasma renin activity and the negative feedback of DOCA on the hypothalamic-hypophyseal-adrenal axis, adrenocortical function of DOCA-hypertensive swine was hyperresponsive to trophic hormones. Results from this study suggest that the DOCA-hypertensive swine may be a valuable model in elucidating the relationship between hypertension and adrenocortical function and in investigating nonclassical control of the adrenal cortex, that is, control exerted during the hypertensive state that exists apart from or in addition to that exerted by ACTH and angiotensin II.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1985

Effects of 100 percent oxygen on the cardiovascular responses to vasoactive compounds in the dog.

Hyperoxia has been shown to disrupt certain membrane bound enzyme systems within the pulmonary endothelium which are responsible for the metabolism of several endogenous vasoactive compounds. This study was to evaluate whether the potential disruption of the prostaglandin dehydrogenase/reductase and angiotensin converting enzymes, as a consequence of hyperoxia, would alter the activation/deactivation of prostaglandins or the angiotensins (I and II) and thereby alter their peripheral cardiovascular actions. Two groups of anesthetized dogs, one group ventilated with ambient air and the other with 100% oxygen, were given bolus injections of angiotensin I, angiotensin II, prostaglandin E2, sodium nitroprusside, and phenylephrine before and during 8 h of exposure to air or oxygen. The hyperoxic animals demonstrated a significant increase in mean arterial pressure responsiveness to both angiotensin I and angiotensin II. The responsiveness to the drugs increased by 41% for angiotensin I and 43% for angiotensin II. The ambient air control dogs showed no significant changes for any compounds tested. These data indicate that with 8 h of hyperoxia the renin-angiotensin system's ability to influence cardiovascular function is augmented, whereas, the hemodynamic effects of prostaglandins are unaltered.

Angiotensin I↗
PubMed1985

Non-invasive blood pressure measurement in Yucatan miniature swine using tail cuff sphygmomanometry.

A relatively new non-invasive method using a photo-electric flow sensor in non-heated animals, was evaluated for its accuracy in measuring systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) in 40-90 Kg normotensive and hypertensive Yucatan miniature swine. Directly measured SBP, DBP and electronically averaged MAP were recorded from chronic arterial catheters simultaneously with indirect pressures, cuff pressure and tail blood flow under various conditions. In all of the tests tail cuff SBP estimation averaged within 5% of directly measured SBP. The correlation of the two methods was significant (r = .95, P less than 0.01). Over a 60 to 202 mmHg range of blood pressure induced pharmacologically or due to DOCA hypertension, the tail cuff SBP was within 4-10% of directly measured SBP. The tail cuff method was also used to determine DBP and MAP. DBP determined from the tail cuff record was found consistently to underestimate the direct measured DBP by approximately 17%. The two methods were correlated (r = .87 P less than 0.01). The measured tail cuff MAP generally underestimated the direct MAP by approximately 5%. The correlation of directly measured MAP and tail cuff methods was significant (r = .72, P less than 0.01). These results indicated that this system may be used to accurately assess blood pressure in miniature swine.

Animals↗
PubMed1984

Mechanism of renin release in exercising dog.

Exercise is associated with an increase in plasma renin activity (PRA). The purpose of this study was to determine the role of the prostaglandin (PG) and adrenergic pathways in the renin release with exercise in the dog. One group of animals (n = 4) was exercised under control untreated and indomethacin- and meclofenamate- (2 mg/kg) treated conditions. A 155% increase in PRA was not influenced by PG inhibition. In a second group (n = 7) PRA was 1.22 +/- 0.32, 3.29 +/- 1.59, 6.28 +/- 2.85, and 5.30 +/- 2.00 ng ANG I X ml-1 X h-1 at rest and during light, moderate, and heavy exercise, respectively. Guanethidine treatment (15 mg/kg) decreased mean PRA by 41, 50, 70, and 73% at rest and during the three levels of exercise, respectively. In a third group (n = 5) control exercise runs were repeated after metoprolol treatment. Selective beta 1-blockade completely abolished the increment in PRA observed with exercise. These data demonstrate that the elevation of PRA during exercise in the dog is mediated by increased sympathetic nerve activity involving beta 1-receptors and that it is not dependent on alterations in PG synthesis.

Animals↗
PubMed1984

Comparison of the effects of sulindac with other cyclooxygenase inhibitors on prostaglandin excretion and renal function in normal and chronic bile duct-ligated dogs and swine.

Sulindac sulfoxide is a prodrug which must be converted to a reduced active metabolite, sulindac sulfide, in order to inhibit arachidonate cyclooxygenase. Oral administration of sulindac sulfoxide does not yield substantial amounts of sulindac sulfide in the urine. To determine whether sulindac sulfide inhibits renal prostaglandin (PG) synthesis, the active form of the drug, sulindac sulfide (5 mg/kg i.v.), was administered to four sham-ligated dogs and four dogs with liver disease induced by chronic (6 weeks) common bile duct ligation (CBDL). In both the sham and CBDL animals the sulindac sulfide caused a 60 to 90% reduction in PGE2, PGF2 alpha and 6-keto-PGF1 alpha excretion rates. In the same animals, subsequent treatment with another cyclooxygenase inhibitor, naproxen (10 mg/kg i.v.), did not result in any further decrease in PGE2 or PGF2 alpha excretion but did decrease 6-keto-PGF1 alpha excretion. In the CBDL animals, sulindac sulfide treatment decreased renal blood flow, glomerular filtration rate and urine volume and resulted in the urinary excretion of large amounts of the sulindac sulfide. Similar changes in PG excretion and renal function were observed in CBDL animals treated solely with naproxen (10 mg/kg i.v.) or with ibuprofen (20 mg/kg i.v.). In four normal and three CBDL animals, we determined that i.v. administration of the prodrug, sulindac sulfoxide (5-15 mg/kg), resulted in plasma levels of 2-5 micrograms/ml of the active drug, sulindac sulfide, only in the CBDL animals. In subsequent experiments, we gave sulindac sulfoxide, 5 mg/kg i.v., to five CBDL dogs and three CBDL miniature swine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Importance of renal prostaglandins in control of renal function after chronic ligation of the common bile duct in dogs.

To explore the possible vasoregulatory role of renal prostaglandins during liver disease, excretory rates of PGE2, PGF2 alpha, and a metabolite of PGI2, 6k-PGF1 alpha, were determined before and after chronic ligation of the common bile duct in 23 dogs. Bile duct ligation for 50 +/- 3.7 days (mean +/- SEM) significantly increased serum bilirubin and alkaline phosphatase. PGE2, PGF2 alpha, and 6k-PGF1 alpha excretion rates were significantly (p less than 0.01) increased following chronic bile duct ligation, by approximately 100%, 80%, and 500%, respectively, with similar increments in both ascitic and nonascitic animals. In 10 sham-ligated animals, PGE2, PGF2 alpha, and 6k-PGF1 alpha excretion rates were unchanged. In 6 dogs sequential measurements of urine prostaglandins indicated that PGE2 and 6k-PGF1 alpha excretion were significantly increased at 2, 4, and 6 weeks after ligation, whereas the increase in PGF2 alpha excretion was not significant until 6 weeks. Indomethacin (2 mg/kg) reduced prostaglandin excretion by 65% to 90% and significantly increased arterial pressure, decreased glomerular filtration rate and renal blood flow, and increased renal vascular resistance from 0.53 +/- 0.09 to 0.90 +/- 0.13 mm Hg/ml/min. Fractional renal blood flow, assessed by microspheres, was disproportionately reduced in the inner cortex after prostaglandin inhibition in the chronic bile duct ligation group. Indomethacin did not significantly alter renal function in sham animals, despite comparable reductions in prostaglandin excretion. These data demonstrate that, in dogs with experimental liver disease produced by chronic bile duct ligation, renal prostaglandin synthesis is increased, and the enhanced synthesis of vasodilatory prostaglandins serves to maintain renal blood flow and glomerular filtration rate.

6-Ketoprostaglandin F1 alpha↗
PubMed1983

Effects of phenoxybenzamine, metoprolol, captopril, and meclofenamate on cardiovascular function in deoxycorticosterone acetate hypertensive Yucatan miniature swine.

Eight adult Yucatan miniature swine were implanted with deoxycorticosterone acetate (DOCA) impregnated silicone strips (100 mg X kg-1). After 16 weeks of DOCA treatment mean arterial pressure (MAP) increased to 183 +/- 4 mmHg (1 mmHg = 133.322 Pa). In four normal animals arterial pressure was 126 +/- 8 mmHg. The increase in MAP in the DOCA animals was due to an elevated total peripheral resistance (TPR) with cardiac output remaining normal. In tests with conscious animals, phenoxybenzamine (1 mg X kg-1) significantly decreased arterial pressure via a selective decrease in TPR. Neither meclofenamate, metoprolol, nor captopril affected MAP in these DOCA hypertensive animals. Dose--response curves to exogenous norepinephrine and angiotensin II revealed that the DOCA animals had an increased pressor sensitivity to both of these agents. These data suggest that in the DOCA hypertensive Yucatan swine an increase in alpha adrenergic activity and (or) an increase in smooth muscle responsiveness to circulating catecholamines is responsible for the increase in blood pressure as a result of an increase in total peripheral resistance.

Animals↗
PubMed1982

Effects of aspirin treatment on kidney function in exercising man.

The effects of aspirin treatment on kidney excretory function were investigated in treadmill-exercised men. Six individuals ran for 30 min at 70% of their maximal oxygen consumption. Exercise tests were conducted for control and aspirin-treated conditions. Aspirin (3.25 g/d) was administered for 3 d prior to testing. Experiments were carried out with the subjects non-hydrated and hydrated (4 ml H2O/kg body weight). Aspirin treatment did not influence the alterations in creatinine clearance, urine volume, osmolar clearance, and/or sodium and potassium excretion seen with exercise. The only effect of aspirin was observed in the recovery samples of the non-hydrated tests in which aspirin treatment significantly decreased urine volume and increased urine specific gravity, osmolality, and the urine/plasma osmolality ratio. These results suggest that aspirin treatment does not have any significant effects on the renal excretory response to short-term moderate exercise.

Adult↗
PubMed1982

Oxygen consumption in treadmill-exercised Yucatan miniature swine.

Oxygen consumption was measured in Yucatan miniature swine during various intensities of treadmill exercise. Nine animals were evaluated at rest and at various treadmill velocities ranging from 2.5-4.5 mph. Oxygen consumption was linearly related to treadmill speed during sub-maximal exercise work loads (r = 0.92, P less than 0.01). Maximal oxygen consumption was also determined in two groups of animals. In one group (N = 6) the highest attainable oxygen consumption was 24.0 +/- 1.31 ml . min-1 . kg-1. In the second group (N = 9) an electric prod was utilized to encourage the animals to run. Their maximal oxygen consumptions ranged from 33.9-51.1 ml . min-1 . kg-1 with a mean of 41.7 +/- 1.8 ml . min-1 . kg-1. These data indicated that Yucatan swine have a relatively low aerobic capacity compared to the rat or dog, but their oxygen consumptions are similar to that observed in untrained man.

Animals↗
PubMed1981

Effects of prostaglandin inhibition on renal function in deoxycorticosterone-acetate hypertensive Yucatan miniature swine.

This study evaluated the effect of prostaglandin (PG) on renal function in normal and deoxycorticosterone-acetate (DOCA) hypertensive Yucatan miniature swine. Eight animals were implanted with DOCA impregnated silicone strips. MAP increased in the conscious DOCA animals from a normal pressure of 110-115 mmHg, to 148 +/- 4 mmHg. After 3-4 weeks, the DOCA hypertensive and eight normal (sham or non-implanted) animals were anesthetized with sodium pentobarbital which reduced MAP in the DOCA pigs to normotensive levels. Under anesthesia, PG inhibition (indomethacin or meclofenamate, 2 mg/kg i.v.) increased MAP only in the normal group (P less than .05). PG inhibition caused a significant reduction in renal blood flow in both groups, but only decreased glomerular filtration rate in the DOCA animals (P less than .05). Radioactive microsphere distribution to the other cortex of the normal animals was significantly decreased with PG inhibition, (P less than .05). No consistent changes in electrolyte excretion or urine flow rate was seen in either group following PG inhibition. These data indicate that PG may influence renal hemodynamics in both normal and DOCA hypertensive Yucatan miniature swine. The finding that PG inhibition selectively decreases GFR in the DOCA animals suggests a possible protective role of these hormones in this hypertensive animal model.

Animals↗
PubMed1981

Changes in renal cortical sialic acids and colloidal iron staining associated with exercise.

The purpose of this study was to determine if exercise was associated with alterations in renal cortical sialic acid content or glomerular capillary anionic character. These factors have been shown to be important, insofar as they contribute to an electrostatic barrier which prevents the filtration of negatively charged macromolecules. In unilaterally nephrectomized dogs (n=7), exercised kidneys tended to have increased amounts of sialic acids and a decrease in glomerular anionic character, as evaluated by the intensity of colloidal iron staining, however, nephrectomy alone also caused similar changes. Additional experiments were conducted using rat litter mates assigned to control or treadmill-exercise groups. Exercised animals were run for 60-80 min. Renal cortical sialic acids were 2.74 +/- 0.07 mumol/g for controls (n=12) and 3.03 + 0.09 mumol/g for the exercised animals (n=10) (P less than 0.05). Colloidal iron staining, rated on a 0-3 scale (0=no uptake, 3=maximum staining) was 2.5 +/- 0.1 and 1.3 +/- 0.3 for the controls and exercised animals, respectively (P less than 0.05). Colloidal iron staining remained below control levels for 24 h post-exercise. These data suggest that exercise increases glomerular sialic acid content and decreases colloidal iron staining. This latter effect may decrease the glomerular capillary electrostatic barrier and thereby may be an important factor in causing exercise proteinuria.

Animals↗
PubMed1980

Renal prostaglandin E2 and D2 alpha secretion and excretion in exercising conscious dogs.

Renal prostaglandin E2 (PGE2) and F2 alpha (PGF2 alpha) secretion and excretion rates were determined in dogs at rest and during various levels of treadmill exercise. Four animals were chronically instrumented to measure mean arterial pressure (MAP), heart rate (HR), left renal blood flow (RBF), and to sample renal venous (RV) blood. In four additional animals, the bladder was cannulated to enable urine collection prior to and after exercise. When compared to resting values, RV PGE2 concentrations increased by 99, 119, and 50 percent during light, moderate and heavy exercise workloads, respectively. RBF was constant during exercise and consequently renal PGE2 secretion increased as a function of RV PGE2 concentration. Similar changes were observed in PGF2 alpha in 2 dogs. When compared to resting values, excretion rates of PGE2 respectively, due to an increase in urine PGE2 and PGF2 alpha concentrations. The data demonstrate that renal PG synthesis, as evaluated by PG secretion and excretion, is increased during exercise in the dog.

Animals↗
PubMed1980

Effect of dichloroacetate on plasma lactic acid in exercising dogs.

Dichloroacetate sodium (DCA) has been shown to reduce circulating levels of lactic acid (LA) under a variety of experimental and clinical conditions. We have examined the effect of DCA on the lactacidemia of exercise in treadmill-exercised dogs. One group of animals (n = 8) was tested at light, moderate, and heavy exercise work loads. Plasma LA, 19 +/- 2mg/dl at rest, increased to 26 +/- 4, 38 +/- 5, and 52 +/- 6 mg/dl during the three workloads, respectively. In the same animals, when identical treadmill tests were conducted after DCA (100 mg/kg, iv), the rise in LA was significantly attenuated. Lactic acid values were 11 +/- 2 mg/dl at rest after DCA and 15 +/- 2, 20 +/- 4, and 23 +/- 3 mg/dl for the light, moderate, and heavy workloads, respectively. Another group of dogs (n = 6) performed prolonged moderate exercise. Under untreated conditions, LA increased from 24 +/- 1 mg/dl at rest, to 41 +/- 6 mg/dl at 10 min, and 50 +/- 5 mg/dl at 50 min. During repeat tests, DCA was given at 12 min when LA was 30 +/- 6 mg/dl. At 50 min, LA was 18 +/- 3 mg/dl or 60% lower than that observed during the untreated run. Because DCA has been shown to increase pyruvate dehydrogenase enzyme activity, these data suggest that this enzyme may be an important factor in LA metabolism during exercise.

Acetates↗
PubMed1980

Failure of prostaglandin inhibition to attenuate the tolerance to hemorrhage in domestic chicken.

Domestic fowl have been shown to have the ability to withstand severe hemorrhage. Recent studies in mammals have suggested that prostaglandin hormones may be beneficial during hemorrhagic shock. It has been reported that chickens have high circulating levels of prostaglandins. Anesthetized chickens were stressed by the removal of 45% of the their estimated total blood volume. When compared to controls, neither prostaglandin inhibition with indomethacin or meclofenamate decreased the ability of these animals to tolerate hemorrhage. Changes in mean arterial pressure following hemorrhage were not altered by prostaglandin inhibition. These data demonstrate that prostaglandins are not responsible for the tolerance to hemorrhage observed in domestic fowl.

Animals↗
PubMed1980

Resting metabolism of Yucatan miniature swine.

Oxygen consumption, carbon dioxide production, rectal temperature and skin temperatures were measured in six conscious Yucatan miniature swine. Heat production was calculated from oxygen consumption and carbon dioxide production data. Under ambient conditions (20 degrees C), the parameters studied were similar to what has been reported for conventional domestic swine. During 90 minutes of cold exposure (0 degrees C), oxygen consumption increased by approximately 50%. At 0 degrees C, excessive shivering and grunting were noticeable and were associated with decreases in skin and rectal temperature.

Animals↗