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J G Umans

Publications and source records attributed to J G Umans.

At least 37 records · Page 2Linked to original sources
PubMed1995

Systemic and gut O2 extraction during endotoxemia. Role of nitric oxide synthesis.

Endotoxin administration decreases intrinsic responsiveness of arteries to contractile agonists, both in vivo and in vitro. Endotoxin also impairs systemic and intestinal ability to increase microvascular O2 extraction in response to decreases in O2 delivery. During endotoxemia, contractile responsiveness can be increased by stereospecific inhibitors of nitric oxide (NO) synthase, suggesting that the hypotension and loss of microvascular function caused by endotoxin may result from increased nitric oxide biosynthesis. This study tested whether inhibition of NO synthesis could reverse the systemic and intestinal oxygen extraction defects seen after endotoxin challenge in the dog. Oxygen extraction and hemodynamic responses to progressive decreases in O2 delivery (stagnant hypoxia) were measured systemically and in isolated autoperfused intestine segments in anesthetized dogs. Systemic and intestinal O2 extractions at the onset of O2 supply dependency were significantly impaired in endotoxin-challenged (n = 6) compared with control (n = 7) animals. Inhibition of NO synthase activity with N omega-nitro-L-arginine methyl ester (L-NAME), 50 mg/kg + 100 mg/kg/h, completely inhibited endothelium-dependent vasodilation responses evaluated in vitro, and significantly but incompletely reversed the systemic hypotension in animals previously given endotoxin (n = 9). Despite this improvement, critical O2 extraction ratios remained significantly reduced. Administration of L-NAME in the absence of endotoxin (n = 8) significantly increased systemic vascular resistance and decreased cardiac output and O2 delivery, but it did not impair critical O2 extraction ratios in whole body or isolated intestine. We conclude that inhibition of NO synthesis in this model of endotoxemia can improve arterial pressure without improving those microvascular functions that may influence tissue O2 extraction efficacy.

Acetylcholine↗
PubMed1994

Exposure of immature rats to hyperoxia increases tracheal smooth muscle stress generation in vitro.

Recently, we demonstrated that chronic exposure to hyperoxia causes in vivo airway muscarinic receptor hyperresponsiveness in the developing rat [Am. J. Physiol. 262 (Lung Cell. Mol. Physiol. 6): L263-L269, 1992]. To test whether airway cholinergic hyperresponsiveness might result from intrinsic alterations in smooth muscle contractility, we measured the effect of in vivo hyperoxia on the contractile force elicited by acetylcholine (ACh) of isometrically mounted tracheal rings in vitro. Tracheal rings were obtained from 3-wk-old rats exposed to air or to > 95% O2 for 8 days. Muscarinic responses were determined by measuring the force elicited by exposure to increasing concentrations of ACh. Responses were normalized to the morphometrically determined tracheal smooth muscle cross-sectional area in a plane perpendicular to the axis of force generation. In vivo O2 exposure significantly increased maximal ACh-induced stress generation (response to 10(-3) M ACh: air, 15.92 +/- 1.37 g/mm2; O2, 21.78 +/- 1.52 g/mm2; P = 0.010). The ACh-induced stress generation of cylinders from hyperoxic rats was substantially reduced by both epithelial removal and treatment with the cyclooxygenase inhibitor indomethacin. We conclude that in vivo hyperoxic exposure increases tracheal smooth muscle contractile function in vitro and that epithelium-derived prostaglandin(s) contributes to the observed increase in maximal contractile responsiveness.

Animals↗
PubMed1993

Measurement of peritoneal dialysis delivery in children.

We measured urea [weekly urea clearance/total body water (KT/Vurea)] and creatinine (CCr) clearances on 35 occasions in 15 stable chronic peritoneal dialysis patients to determine the feasibility and reproducibility of such measurements in children. In addition, we performed peritoneal equilibration tests (PETs) to characterize our patients' peritoneal membranes and to estimate weekly clearances. We demonstrated that dialysis delivery can be quantified by these standard measurements in children of widely varying size. Further, we found that clearances predicted from PET data were similar to measured values in all patients. However, predicted and measured values were most significantly correlated in patients with high and high-average peritoneal membrane permeability. KT/Vurea and CCr were correlated overall, but differences in scaling affected the validity of the relationship. When both clearances were scaled to weight, the correlation was closer, but still differed between PET-determined peritoneal membrane types.

Adolescent↗
PubMed1993

Glomerular disease and urinary Sézary cells in cutaneous T-cell lymphomas.

We report three cases of biopsy-documented renal glomerular disease occurring in patients with cutaneous T-cell lymphomas. One patient had immunoglobulin A (IgA) nephropathy and another had membranous nephropathy. The remaining patient had an immune complex glomerulonephritis without immunofluorescent evidence of IgA, but with mesangial deposits and a clinical course notable for stable renal function, minimal proteinuria, and episodic gross hematuria of renal origin. These three cases, along with IgA nephropathy in two of the four previously reported cases, suggest a possible association between cutaneous T-cell lymphoma and this glomerular lesion. In addition, Sézary cells were observed in the urine of two patients, one without evidence of glomerular disease. The prognostic value of this new observation is unknown.

Adult↗
PubMed1993

Effects of endotoxin in vivo on endothelial and smooth-muscle function in rabbit and rat aorta.

In order to determine whether endotoxemia induced generalized defects in vascular contraction and endothelium-dependent relaxation, we studied the effect of in vivo endotoxin administration in Sprague-Dawley rats and New Zealand White rabbits on endothelial and arterial smooth-muscle responses of isolated thoracic aorta in vitro. Endotoxin treatment significantly decreased contractile responses to phenylephrine (PE), angiotensin II (AII), serotonin (5-HT), and potassium chloride. This effect was not altered by indomethacin or endothelial denudation. Treatment of vessels with NG-nitro-L-arginine (NNLA), an inhibitor of arginine-dependent nitric oxide biosynthesis, or with methylene blue, an inhibitor of soluble guanylate cyclase, resulted in significant improvement of the contractile defect in endotoxin-treated vessels. The restorative effect of NNLA on contractile responses in endotoxin-treated aortic rings was similar in the presence or absence of an intact endothelium. Endothelium-dependent relaxation in response to acetylcholine, substance P, or the calcium ionophore A23187 was markedly impaired in vessels from endotoxin-treated rabbits, while endothelium-independent relaxation in response to nitroprusside was similar in both groups. These results suggest that endotoxemia both induces basal, nonendothelial nitric oxide synthesis and impairs the agonist-stimulated release of endothelium-derived relaxing factor (EDRF). These findings may have mechanistic importance in the hemodynamic derangements of endotoxemia.

Angiotensin II↗
PubMed1993

Phosphate kinetics during high-flux hemodialysis.

Phosphate clearance by polysulfone (PS) and cuprophane (CU) membranes and the relationship of peridialytic changes in serum phosphate with those of serum-ionized calcium, parathyroid hormone (PTH), and insulin were studied in six stable patients undergoing chronic hemodialysis (HD). Dietary phosphate intake was 25.7 mmol/day, and total dose of elemental calcium was 3.2 g/day. Patients were dialyzed for 2 to 4 h, once with each membrane. Serum phosphate levels fell precipitously during the first hour of HD with both dialyzers, from 1.42 and 1.49 mM to nadirs of 0.53 and 0.69 mM for PS and CU, respectively. Phosphate levels began to increase either late in HD or at the end of HD and, by 4 h post-HD, did not differ from predialysis values. Total mass transfer of phosphate was greater during the first hour (3.4 and 3.2 mmol for PS and CU, respectively) than during the remainder of HD (2.4 and 2.6 mmol/h). There were no significant differences in intradialytic serum phosphate changes, postdialytic phosphate rebound, or total phosphate removal between the two dialyzers. Ionized calcium increased by 0.11 mM, and PTH was suppressed to 40 to 50% of baseline values during dialysis with either membrane. Although phosphate removal continued for the duration of dialysis, serum phosphate did not continue to decrease, either reaching an apparent steady state or beginning to rebound, even during dialysis. This suggests active phosphate mobilization from a pool other than the extracellular fluid and demonstrates the inadequacy of a one-compartment model to explain these data. Further, these data do not support the regulation of intradialytic phosphate mobilization by serum PTH or insulin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Extracellular calcium and intrinsic tone in the human umbilical artery.

Previous in vitro studies of the human umbilical artery (HUA) have suggested that this vessel exhibits significant intrinsic tone, even in the absence of contractile agonists. Other investigators have found that these vessels are unresponsive to nitrovasodilators, suggesting that the guanylate cyclase-mediated relaxation mechanism may not be operative. To clarify these observations, human umbilical cords were obtained at the time of delivery and HUA rings were studied in organ baths. In contrast to other systemic arteries, HUA rings exhibited unstable initial tone in the absence of pharmacologic agonists. This intrinsic tone was augmented when the extracellular ionized calcium concentration was increased and abolished when extracellular calcium was removed. Rings maintained in the presence of extracellular calcium for 1 hr became less responsive to changes in extracellular calcium than did rings maintained in calcium-free buffer. Serotonin produced oscillatory, quantal contractions in the presence of calcium; in the absence of extracellular calcium, it elicited only concentration-dependent graded contractions. In the presence of nifedipine or in the absence of extracellular calcium, nitroglycerin fully relaxed contractions elicited by serotonin. Thus, in HUA, extracellular calcium produces intrinsic tone that diminishes spontaneously with time.

Calcium↗
PubMed1992

L-canavanine selectively augments contraction in aortas from endotoxemic rats.

Contractile responses to KCl or phenylephrine were inhibited in endothelium-denuded aorta from endotoxin-treated rats. L-Canavanine, a selective inhibitor of inducible nitric oxide synthase, augmented contractile responses in vessels from endotoxin, but not saline-pretreated animals. In contrast to nitroarginine, L-canavanine did not inhibit endothelium-dependent relaxation induced by acetylcholine. Selective inhibitors of inducible nitric oxide synthase may be useful probes of vascular dysfunction in sepsis.

Animals↗
PubMed1992

Vancomycin elimination during high-flux hemodialysis: kinetic model and comparison of four membranes.

Vancomycin clearance was measured in five patients during dialysis with cuprophane (CU), polysulfone (PS), cellulose triacetate (CT), and polyacrylonitrile (PAN) dialyzers. Vancomycin was significantly cleared during routine high-flux (HF) hemodialysis (HD) with the latter three membranes, but not by CU. Postdialytic rebound of serum vancomycin concentrations was noted following HF dialysis, necessitating use of a two-compartment pharmacokinetic model. Measurement of serum vancomycin concentration immediately postdialysis significantly overestimates intradialytic removal, possibly resulting in inappropriate dose adjustment. Vancomycin infusion during HF HD results in significant drug removal during its administration to the patient, complicating the calculation of an adequate dose.

Acrylic Resins↗
PubMed1992

Direct effects on airway smooth muscle contractile response caused by endothelin-1 in guinea pig trachealis.

Endothelin-1 (ET-1), a peptide derived from vascular endothelial cells, causes tracheal smooth muscle (TSM) relaxation followed by sustained contraction when administered intravenously in guinea pigs by a mechanism that depends upon an intact airway epithelium. To elucidate the potential role of the epithelium in modulating the response to ET-1 and the potential effects of local release of ET-1, we studied the effects of topical application of ET-1 to a segment of TSM in situ. An epithelium smooth muscle preparation that does not disrupt normal anatomic relationships was used; smooth muscle contraction was measured isometrically in vivo. Application of 10(-10) mol/cm2 ET-1 to the epithelial surface in six animals caused 2.27 +/- 0.45 g/cm active tension (AT) of the TSM segment after 30 min (p less than 0.05 versus baseline); an initial relaxation response was not observed. Endothelin-1 was dose-dependent and was 1,000 times more potent than acetylcholine in causing AT in TSM. Pretreatment with ET-1 did not alter the subsequent response to acetylcholine. Contraction elicited by topical application of ET-1 persisted greater than 3 h. In five animals in which the epithelium was removed, 10(-10) mol/cm2 ET-1 caused 4.45 +/- 0.92 g/cm AT after 30 min (p less than 0.05 versus intact epithelium). These data suggest that topical application of ET-1 elicits responses that are different from those elicited in the same preparation after intravenously administered ET-1: (1) TSM contraction that is not preceded by a transient relaxation phase, and (2) contraction that is not reduced after removal of the epithelium.

Acetylcholine↗
PubMed1991

Epithelial modulation of airway smooth muscle response to endothelin-1.

We investigated the role of epithelial modulation of contraction caused by endothelin-1 in airway smooth muscle in guinea pigs in situ. Airway responses were assessed isometrically as tracheal force and simultaneously as change in lung resistance. Intravenous administration of 10(-8) mol/kg endothelin-1 caused a biphasic response in tracheal active tension: initial relaxation (-0.82 +/- 0.22 g/cm after 30 s, p less than 0.05 versus baseline) followed by contraction (1.65 +/- 0.28 g/cm after 7 min, p less than 0.05 versus baseline). Endothelin-1 also elicited immediate bronchoconstriction; lung resistance increased from 0.148 +/- 0.030 to 0.992 +/- 0.274 cm H2O/L/s (p less than 0.005) after 10(-8) mol/kg endothelin-1 given intravenously. Active tension elicited by 10(-8) mol/kg endothelin-1 after removal of the epithelium from the tracheal segment (0.59 +/- 0.16 g/cm) was less than in segments with an intact epithelium (1.65 +/- 0.28 g/cm, p less than 0.01). Both tracheal contraction and bronchoconstriction were attenuated by pretreatment with indomethacin orally, BW 755C intravenously, or substitution of endothelin-C-terminal hexapeptide for endothelin-1. However, the initial tracheal relaxation response was similar after each intervention. These data suggest actions of endothelin-1 that have not been demonstrated previously: (1) endothelin-1 elicits a biphasic response in tracheal smooth muscle (an initial relaxation response elicited by the carboxy-terminal residues and a later contractile response that requires synthesis of a cyclooxygenase mediator) and (2) epithelium adjacent to the airway smooth muscle modulates contraction elicited by endothelin-1.

Animals↗
PubMed1990

Pressor effect of endothelium-derived relaxing factor inhibition in conscious virgin and gravid rats.

We used pressor responses to N-methylarginine (NMA), a specific inhibitor of endothelium-derived relaxing factor (EDRF) biosynthesis, to assess the contribution of EDRF to control of basal blood pressure in conscious, chronically instrumented virgin and gravid rats. Hypotheses were that NMA would raise blood pressure in conscious animals in spite of intact cardiovascular reflexes and that differing effects in virgin and pregnant animals would reveal contributions of EDRF to the physiological vasodilation of pregnancy. Basal mean arterial pressure (MAP) and heart rate (HR) were 106 +/- 12 mmHg and 394 +/- 27 beats/min (n = 31) in virgin and 102 +/- 8 mmHg and 378 +/- 18 beats/min (n = 14) in gravid rats. After NMA (150 mg/kg iv), increments in MAP and decreases in HR were similar in each group (virgin, delta MAP = 38 +/- 12 mmHg, delta HR = -65 +/- 27 beats/min, n = 14; gravid, delta MAP = 33 +/- 8 mmHg, delta HR = -63 +/- 20 beats/min, n = 6). Pretreatment with excess L-arginine reduced pressor responses to NMA by 80% in both pregnant and virgin animals. In contrast, L-arginine had no significant effect on the pressor response to phenylephrine (6.4 mg/kg iv). EDRF contributes importantly to regulation of basal blood pressure in conscious animals, and pregnancy does not alter the pressor effect of EDRF inhibition in the rat.

Animals↗
PubMed1990

Endotoxin in vivo impairs endothelium-dependent relaxation of canine arteries in vitro.

We studied the effect of endotoxin administration in vivo on arterial smooth muscle responses in vitro, testing the hypotheses that endotoxin augments adrenergic vasoconstriction and impairs endothelium-dependent vascular relaxation. Ten mongrel dogs were anesthetized and mechanically ventilated. Five received a bolus infusion of Escherichia coli endotoxin (5 mg/kg), and the remainder received a sham infusion. After 4 to 5 h, the anesthetized dogs were rapidly exsanguinated, and femoral, renal, and superior mesenteric arteries were removed. Arterial rings were mounted on force transducers in organ baths; contraction to phenylephrine or potassium-substituted Krebs-Henseleit solution (KCl), and relaxation to nitroprusside or acetylcholine were studied. Smooth muscle contractions to phenylephrine or KCl were similar between sham and endotoxin for each agonist. Also, nitroprusside-elicited relaxation from half-maximal phenylephrine-elicited contraction was similar. However, relaxation elicited by acetylcholine was markedly impaired in vessels from endotoxin-treated dogs. The negative log molar concentration of acetylcholine producing 50% relaxation for femoral arteries was 7.38 +/- 0.11 (endotoxin) versus 8.09 +/- 0.12 (control, p = 0.002), for renal arteries it was 6.71 +/- 0.33 (endotoxin) versus 7.81 +/- 0.18 (control, p = 0.019), and for mesenteric arteries it was 7.27 +/- 0.03 (endotoxin) versus 7.95 +/- 0.15 (control, p = 0.002). These results demonstrate that endotoxin treatment impairs endothelium-dependent relaxation of canine arteries in vitro. The data suggest that vascular changes in endotoxemia are accompanied by alteration in endothelial cell function, perhaps through altered endothelial production of vasodilatory mediators.

Acetylcholine↗
PubMed1988

Dual action of morphine on fetal breathing movements.

Morphine has been reported to both stimulate and suppress fetal breathing movements (FBM). In light of these conflicting reports, we have conducted a systematic dose-response analysis of the effects of morphine on FBM in 27 fetal lambs. Morphine was infused directly to the fetus in doses ranging from 0.075 to 80 mg/hr. Low doses (0.075-2.5 mg/hr) resulted in a progressive increase in the relative incidence of FBM, whereas higher doses (greater than 2.5 mg/hr) decreased FBM with total apnea observed at 80 mg/hr. This biphasic response can be fitted as the sum of two sigmoidal log dose-response curves. Both stimulation and suppression of FBM by morphine were abolished by naloxone pretreatment, indicating that both responses are mediated by activation of opioid receptors. The dual action of morphine on FBM may be due to different opioid receptor subtypes or different sites of action.

Animals↗
PubMed1986

Effects of thyrotropin-releasing hormone in the fetal lamb.

Thyrotropin-releasing hormone causes neurobehavioral arousal and stimulates breathing in adult, newborn, and preterm experimental animals. Its effects on behavioral state, breathing, blood pressure, and heart rate were studied in the chronically instrumented late term fetal lamb. Fetal intravenous administration of thyrotropin-releasing hormone resulted in behavioral arousal with electrocortical desynchronization, increased body and eye movements, rapid and deep breathing movements, and a transient bradycardia followed by prolonged tachycardia, associated with an increase in both systolic and diastolic blood pressure. The effects were similar following intracisternal administration of thyrotropin-releasing hormone. The effects of thyrotropin-releasing hormone on behavior, but not breathing, was abolished in the presence of muscarinic blockade. Thyrotropin-releasing hormone may play a role in the modulation of central regulation of cardiovascular, respiratory, and behavioral activity in the fetus.

Animals↗
PubMed1985

The development of electrocortical activity in the fetal and neonatal guinea pig.

We have developed techniques for chronic recording of electrocortical activity in the fetal and neonatal guinea pig with subsequent power spectral analysis. Thirty-four unanesthesized, unrestrained pregnant Hartley guinea pigs were studied 1 to 14 days following surgical procedures. Twelve neonatal animals instrumented during the first week of life were studied at 3 to 30 days. Spontaneous, undifferentiated electrocortical activity was recorded from the youngest fetuses studied, with high-voltage slow activity appearing at 50 days' gestation. Cycling electrocortical activity and sleep spindles could be observed in the late-term fetal and neonatal animals, with rapid eye movements and behavioral state defined in the latter. Power spectral analysis demonstrated more predominant delta activity, faster beta frequencies, and better-developed sleep spindles in the neonatal animal as compared to the fetus.

Analog-Digital Conversion↗
PubMed1985

The graded and quantal nature of opioid analgesia in the rat tailflick assay.

Opioid agonists routinely increase the latency to respond in the rodent tailflick assay. The nature of this effect was investigated in 5 experiments using several parametric variations and routes of administration. Morphine and methadone were found to produce both quantal and graded effects in all experiments. In cases where quantal effects were observed, the majority of animals also responded in a graded manner during subsequent testing. The increase in latency to respond in the tailflick assay produced by opioid agonists is not accurately characterized as predominantly quantal.

Animals↗