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S L Linas

Publications and source records attributed to S L Linas.

At least 55 records · Page 3Linked to original sources
PubMed1988

Neutrophils accentuate ischemia-reperfusion injury in isolated perfused rat kidneys.

The contribution of neutrophils to reperfusion injury after ischemia is not known. To determine the effect of neutrophils on the function of ischemic kidneys, we added purified human neutrophils during perfusion of isolated ischemic or nonischemic rat kidneys. Reperfusion of ischemic kidneys with neutrophils caused a distinct morphological lesion of vascular endothelial and smooth muscle cells and more functional injury than reperfusion with buffered albumin alone; with neutrophils, glomerular filtration rate (GFR) was 113 +/- 7 microliter.min-1.g-1, tubular sodium reabsorption (TNa) was 72 +/- 2%; without neutrophils, GFR was 222 +/- 18 microliter.min-1.g-1; TNa was 90 +/- 2%; both P less than 0.01 vs. reperfusion with neutrophils. In contrast, addition of neutrophils did not injure control kidneys, unless the neutrophil activator, phorbol myristate acetate, was also added. Two experiments suggested that O2 metabolites contributed to neutrophil-mediated injury to ischemic kidneys. First, reperfusion of ischemic kidneys with O2 metabolite-deficient neutrophils from a patient with chronic granulomatous disease did not cause more injury than reperfusion with buffered albumin alone. Second, simultaneous addition of the O2 metabolite scavenger, catalase, prevented the GFR and TNa decreases caused by neutrophils but did not decrease injury in the absence of neutrophils. We conclude that neutrophils by an O2 metabolite-dependent mechanism contribute to ischemia-reperfusion injury in the isolated perfused kidney.

Animals↗
PubMed1988

The milk-alkali syndrome in pregnancy. Case report.

We present a case of the milk-alkali syndrome occurring in pregnancy, an association not described in the medical literature. Ingestion of calcium carbonate and calcium-containing food was precipitated by the hyperemesis of pregnancy. Complications--hypercalcemia, dehydration, renal insufficiency, and pancreatitis--resolved within days. Here, the milk-alkali syndrome was the cause of the hypercalcemia of pregnancy. This case illustrates a rare cause of and complications from the milk-alkali syndrome.

Adult↗
PubMed1987

Mechanism of decreased vascular response to angiotensin II in renal vascular hypertension.

Compared to many forms of hypertension, vascular reactivity to angiotensin II (AII) is decreased in the early phase of two-kidney, one clip (2-K, 1C) renovascular hypertension (RVH). To determine the role of the AII receptor, we examined vascular responsiveness and 125I-AII binding to mesenteric artery membrane fractions after three weeks of 2-K, 1C RVH. Systolic blood pressure was 165 +/- 8 in RVH and 105 +/- 4 mm Hg in controls, P less than 0.001. Plasma renin activity was 4.2 +/- 0.6 in RVH and 1.4 +/- 0.5 ng AI/ml/hr in controls, P less than .001. The pressor response to exogenous AII was reduced by 40% in RVH. Since administration of a single dose of converting enzyme inhibitor (CEI) did not normalize the response to exogenous AII, the decreased reactivity was not caused by receptor occupancy. 125I-AII binding to mesenteric arteries was equal to or greater in RVH than controls at all concentrations of AII. Scatchard analysis revealed an increase in the total number of binding sites (BMAX): 140.8 +/- 6.3 in RVH versus 91.7 +/- 6.5 fmol/mg in controls, P less than 0.01, while the apparent dissociation constant was unchanged. To determine if the increase in circulating AII caused these binding alterations, rats were either treated with CEI for three days; or unilaterally nephrectomized. Both of these manipulations reversed the decrease in vascular responsiveness as well as the increase in receptor number (BMAX = 136 +/- 13.4 in RVH vs. 94 +/- 9.4 fmol/mg in RVH + nephrectomy, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1987

O2 metabolites cause reperfusion injury after short but not prolonged renal ischemia.

Toxic O2 metabolites have been postulated to contribute to renal ischemia-reperfusion injury, but their biochemical assessment and contribution as a function of the duration of ischemia is unclear. To address this issue we measured renal function and renal cortical glutathione levels following 20, 30, or 45 min of ischemia in situ and then 60 min of reperfusion by the isolated kidney technique. Increasing durations of ischemia were associated with progressive decreases in perfusion flow rate, glomerular filtration rate, tubular Na reabsorption, and renal cortical glutathione following reperfusion. However, reperfusion following simultaneous addition of the permeable O2 metabolite scavenger dimethylthiourea (DMTU; but not urea) prevented glutathione consumption and attenuated reperfusion-induced injury after 20 and 30 min of ischemia. In contrast, reperfusion with DMTU prevented glutathione consumption but did not improve renal function after 45 min of ischemia. Similarly, reperfusion with dimethyl sulfoxide also attenuated renal injury after 20 and 30 min, but not after 45 min of ischemia. Thus reperfusion of kidneys made ischemic for 20 or 30 min is associated with decreases in tissue glutathione and renal function that were both inhibitable by addition of O2 metabolite scavengers during reperfusion. In contrast, addition of O2 metabolite scavengers during reperfusion of kidneys previously made ischemic for 45 min prevented decreases in glutathione but did not improve renal function. We conclude that O2 metabolites formed during reperfusion contribute to functional impairment in kidneys made ischemic for short durations up to 30 min) but that after prolonged ischemia (greater than 30 min) injury is primarily mediated by non-O2 metabolite-dependent cellular events.

Animals↗
PubMed1987

O2 metabolite-mediated injury in perfused kidneys is reflected by consumption of DMTU and glutathione.

The contribution of toxic oxygen (O2) metabolites to ischemic renal injury is unclear because they have not been added directly to the kidney and few ways exist to effectively measure and assess the effect of these highly reactive products in biological systems. Our goal was to determine the effect of hydrogen peroxide (H2O2) or H2O2-derived products on renal function and to determine whether H2O2-mediated renal injury was reflected by consumption of dimethylthiourea (DMTU) (an exogenous O2 metabolic scavenger), depletion of renal cortical total glutathione (an endogenous O2 metabolite scavenger), and/or adenosine triphosphate (ATP). We found that addition of glucose oxidase (GO) or H2O2 to isolated perfused rat kidneys caused injury that was manifested by decreases in glomerular filtration rate, perfusion flow rate, and sodium reabsorption and that was prevented by addition of catalase (CAT) (but not inactivated CAT) or large doses of DMTU (15 mM), but not urea (15 mM). To further ascertain if the protective effect of DMTU was due to reacting with a scavenging H2O2, we conducted parallel experiments in which we measured the consumption of smaller doses of DMTU (1 mM) in kidneys perfused with GO or H2O2. We found that addition of increasing concentrations of H2O2 decreased DMTU concentration. Renal cortical total glutathione and ATP levels were also decreased by addition of GO or H2O2. In contrast to perfusion with GO or H2O2, perfusion with elastase or collagenase also caused renal injury and decreases in ATP but did not decrease DMTU concentration or tissue total glutathione. We conclude that H2O2 or H2O2-derived products are acutely toxic to the kidney and that decreases in perfusate DMTU concentration and tissue total glutathione, but not tissue ATP, may be useful for specifically assessing the presence and/or toxicity of H2O2 in renal and other biological systems.

Adenosine Triphosphate↗
PubMed1986

Peritoneovenous shunt in the management of the hepatorenal syndrome.

The hepatorenal syndrome (HRS) is a terminal complication of severe liver disease associated with a mortality of 80 to 90%. Although the renal functional abnormalities in the HRS suggest prerenal azotemia, volume expansion with saline, albumin or ascitic fluid rarely results in reversal of the HRS because fluid redistributes from the vascular space. Since the peritoneovenous (PV) shunt causes sustained central volume expansion, it has been advocated for the treatment of the HRS. We prospectively compared the PV shunt (N = 10) to Medical Therapy (MED) (N = 10) on renal function and mortality in 20 patients with the HRS associated with alcoholic liver disease. The HRS was diagnosed on the basis of clinical, hemodynamic, and laboratory criteria. The insertion of a PV shunt resulted in an increase in pulmonary capillary wedge pressure (4.2 +/- 1.1 vs. -1.5 +/- 1.0 mm Hg, P less than 0.01) and in cardiac index (0.8 +/- 0.3 vs. -0.2 +/- 0.3 1/min/m2, P less than 0.05). After 48 to 72 hours, weight (+3.1 +/- 1.1 kg) and serum creatinine (3.9 +/- 0.5 to 5.5 +/- 0.7 mg/dl, P less than 0.001) were increased with MED therapy and decreased (weight: -3.7 +/- 0.7 kg; serum creatinine: 3.6 +/- 0.4 to 3.0 +/- 0.5, P less than 0.05) with the PV shunt. Despite improvement in renal function, only one patient with the PV shunt had prolonged survival (210 days). In the remainder, survival was 13.8 +/- 2.2 days compared to 4.1 +/- 0.6 days with MED therapy. We conclude that the PV shunt often stabilizes renal function, but does not prolong life in patients with the HRS.

Adult↗
PubMed1986

Prevention of hypercalcemia-induced renal concentrating defect and tissue calcium accumulation.

The mechanism of the concentrating defect of hypercalcemia is explored by examining the effect of concomitant phosphate restriction. Rats were pair fed a normal phosphorus diet, without (group 1) or with dihydrotachysterol (group 2), or a low-phosphorus diet (group 3). Hypercalcemia was comparable in groups 2 (12.1 +/- 0.6 mg/dl) and 3 (11.8 +/- 0.4 mg/dl), but serum phosphate was lower in group 3 than group 2 (3.8 +/- 0.7 vs. 7.1 +/- 1.1 mg/dl, P less than 0.005). Group 2 rats had impaired maximum urinary concentration after 24 h of fluid deprivation (2,441 +/- 450 mosmol/kg H2O, P less than 0.001) compared with group 1 (3,263 +/- 466 mosmol/kg H2O) or group 3 (3,332 +/- 515 mosmol/kg H2O) animals. Polydipsia and polyuria were found in group 2 rats only. Tubular calcium reabsorption was higher in group 2 (83.1 +/- 33.5 mg/24 h, P less than 0.001) than group 1 (47.0 +/- 26.1 mg/24 h) or group 3 (52.8 +/- 19.3 mg/24 h) animals, and medullary calcium concentration was higher in group 2 (7.57 +/- 3.08 nmol/mg dry wt, P less than 0.05) as compared to group 1 (5.04 +/- 1.37 nmol/mg dry wt) or group 3 (5.32 +/- 0.98 nmol/mg dry wt) rats. Total medullary solute concentration was significantly higher in group 3 than group 2 animals. Thus phosphate restriction prevents the defect of urinary concentrating ability of chronic hypercalcemia, probably by decreasing tubular uptake and tissue accumulation of calcium.

Animals↗
PubMed1986

Potassium depletion ameliorates hypertension in spontaneously hypertensive rats.

The hemodynamic effect of moderate K+ depletion in hypertension is unknown. Since severe K+ depletion reduces systemic vascular resistance in normotensive rats, we determined the effect of K+ depletion on the natural history of hypertension in spontaneously hypertensive rats (SHR). Wistar-Kyoto rats (WKY) and SHR were fed a K+-replete, a moderately K+-depleted, or a severely K+-depleted diet. After 6 weeks, systemic vascular resistance was reduced by 25% in WKY on the severely K+-depleted diet while mean arterial pressure and systemic vascular resistance were comparable in WKY on the other two diets. In SHR on the severely K+-depleted diet for 6 weeks, muscle K+ was reduced by 23% and growth rate by 65%. In SHR on the moderately K+-depleted diet, growth rate was reduced by 23% after 3 weeks. By 6 weeks, however, muscle K+ was reduced by 5 to 6% and growth rate was comparable to that in SHR receiving the K+-replete diet. The administration of either K+-depleted diet prevented the development of hypertension (systolic blood pressure: severely depleted, 116 +/- 4; moderately depleted, 122 +/- 3; K+-replete, 155 +/- 5 mm Hg; p less than 0.001 compared with both K+-depleted groups) and reversed established hypertension (systolic blood pressure: severely depleted, 116 +/- 4; moderately depleted, 128 +/- 3; K+-replete, 171 +/- 5 mm Hg; p less than 0.001 compared with both K+-depleted groups). The protective effect of K+ depletion was mediated by a 40% reduction in systemic vascular resistance. These results suggest that K+ depletion has a potent antihypertensive effect in SHR.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Hydrogen peroxide causes dimethylthiourea consumption while hydroxyl radical causes dimethyl sulfoxide consumption in vitro.

Addition of increasing concentrations of hydrogen peroxide (H2O2) caused progressive decreases in dimethylthiourea (DMTU) concentrations which were inhibitable by simultaneous addition of catalase, but not the superoxide anion (O2-.) scavenger, superoxide dismutase (SOD), or hydroxyl radical (.OH) scavengers, such as mannitol, sodium benzoate or dimethyl sulfoxide (DMSO). In parallel, addition of increasing concentrations of H2O2 with FE++/EDTA (but not H2O2 alone) caused decreases in DMSO concentrations which were inhibitable by simultaneous addition of .OH scavengers but not SOD or catalase. Addition of DMTU, but not DMSO, also decreased H2O2 concentrations in vitro. The results indicate the relative scavenging specificities of DMTU and DMSO for H2O2 and .OH, respectively. The findings also suggest that measurement of DMTU or DMSO consumption could help assess the contribution of O2 metabolites in biological systems.

Chromatography, Gas↗
PubMed1985

Sodium chloride pica secondary to iron-deficiency anemia.

A young woman was referred for nephrologic evaluation of hypertension and a curious desire for table salt. Suspicion of iron-deficiency anemia arose only after it was determined that sodium balance was achievable during supervised sodium restriction. This salt craving abated within 2 weeks of initiation of iron replacement therapy. Although pica is a common manifestation of iron deficiency, this appears to be the first reported case of salt pica secondary to iron deficiency.

Adult↗
PubMed1985

Effect of potassium depletion on two-kidney, one-clip renovascular hypertension in the rat.

There is considerable controversy about the hemodynamic effect of potassium in hypertension. To determine if K depletion could alter the control of blood pressure, studies were performed in rats with 2-kidney, 1-clip renovascular hypertension (RVH) after 3 to 6 wks of severe and moderate K depletion. After application of a 0.23 mm clip to the left renal artery, rats were placed on a K-replete (KR) (240 mEq/kg), a moderately K-depleted (KDM) (59 mEq/kg), or a severely K-depleted (KDS) (5 mEq/kg) diet. After 3 wks, mean arterial pressure (MAP) reached 154 +/- 3 in KR but only 121 +/- 2 in KDM (P less than 0.01) and 106 +/- 4 mm Hg in KDS (P less than 0.001). After 6 wks, MAP was 160 +/- 8 in KR, but only 132 +/- 5 in KDM (P less than 0.01) and 129 +/- mm Hg in KDS (P less than 0.01). Plasma K at 3 wks was 4.1 +/- .1 in KR, but only 3.5 +/- .1 in KDM (P less than 0.05) and 2.3 +/- .1 mEq/liter in KDS (P less than 0.001). This was associated with an 8% decrease in muscle K in KDM and a 16% decrease in muscle K in KDS. Although KDS animals did not grow during the 6 wks of study, KDM rats gained 60% as much weight at 3 wks, and, by 6 wks, weight gain was comparable in KDM (101 +/- 9) and KR (110 +/- 9 g) animals (P = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Water intoxication in a psychotic patient with normal renal water excretion.

A psychotic patient with hyponatremia and obtundation following short-term ingestion of large amounts of water was found to have maximally dilute urine, and underwent brisk diuresis until the serum osmolality returned to normal. This is the first report of normal renal diluting capacity as documented by measurement of urine osmolality in a water-intoxicated, schizophrenic patient, and demonstrates that normal renal diluting mechanisms may on occasion be overwhelmed by massive water ingestion.

Adult↗
PubMed1984

Role of angiotensin II, alpha-adrenergic system, and arginine vasopressin on arterial pressure in rat.

Three pressor systems regulate arterial pressure (MAP): angiotensin II (ANG II), the alpha-adrenergic system, and arginine vasopressin (AVP). In this study we determined the ability of each system to support MAP in the conscious rat when the other two systems were inactivated. After administration of the converting-enzyme inhibitor teprotide (CEI) and the alpha-adrenergic receptor antagonist phenoxybenzamine (POB), MAP decreased 40% as a result of a 45% decrease in peripheral vascular resistance (PVR). Despite hypotension, plasma AVP levels were not increased, and an AVP pressor antagonist (AVP-A) did not result in a further decrease in MAP. Thus the profound hypotension after POB plus CEI was the result of inhibition of all three systems. POB, rather than CEI, prevented AVP release since following hypotensive hemorrhage, plasma levels reached 51 +/- 13 pg/ml with CEI but only 4.7 +/- 0.8 pg/ml with POB. To study the pressor effect of AVP alone, AVP was infused in POB plus CEI-treated rats. AVP increased MAP (from 68 +/- 4 to 92 +/- 5 mmHg; P less than 0.005) and plasma AVP (to 13.8 +/- 1.9 pg/ml). Since POB inhibited both the AVP and the alpha-adrenergic system, the role of ANG II alone was determined in POB-treated rats. In the presence of ANG II MAP was 97 +/- 1 mmHg. To study the alpha-adrenergic system, MAP was determined in CEI plus AVP-A-treated rats. In the presence of an intact alpha-adrenergic system MAP was 101 +/- 1 mmHg. We conclude that PVR and MAP are profoundly decreased in the absence of all three pressor systems.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1984

Role of prostaglandins in renin secretion in the isolated kidney.

Prostaglandins (PG) stimulate renin secretion through a mechanism that does not require activation of the intrarenal vascular, macula densa (MD), or beta-adrenergic receptors. In the present study the isolated perfused rat kidney was used to study the role of PG as a mediator of renin secretion when extracellular calcium was decreased and after activation of each of the intrarenal receptors. A decrease in extracellular calcium resulted in an increase in renin (from 2.1 to 4.5 ng ANG I/ml, P less than 0.01) and a decrease in PGE2 excretion (from 102 to 44 pg X min-1 X g-1, P less than 0.01). PG synthesis inhibition with indomethacin did not attenuate the increase in renin secretion. Following beta-receptor stimulation with isoproterenol, there was an increase in renin (from 2.1 to 6.6 ng ANG I/ml, P less than 0.01) not associated with changes in PGE2 excretion and not prevented by PG inhibition. When the isolated vascular receptor was stimulated by perfusing either filtering or nonfiltering kidneys below the autoregulatory range of pressure, both renin and PGE2 production were increased, and the increases were prevented by PG inhibition. The MD was activated by three methods: eliminating distal nephron fluid delivery by perfusing with hyperoncotic albumin; perfusing at 60 mmHg in the presence of papaverine; and limiting chloride transport by partially replacing chloride with nitrate in the perfusate. In each circumstance renin and PGE2 production were increased and the increase was prevented by PG inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Mechanism of decreased vascular reactivity to angiotensin II in conscious, potassium-deficient rats.

Chronic potassium deficiency in the rat results in a decrease in the pressor sensitivity to exogenous angiotensin II (AII). To define the mechanism of this resistance to AII, studies were performed in conscious rats after 14-21 d of dietary potassium deficiency. The pressor response to graded doses of AII was 50% less in potassium-deficient than control animals. In contrast, the pressor response to graded doses of norepinephrine was preserved in potassium-deficient rats; therefore, the decreased response to AII was not due to a generalized defect in vascular reactivity. Pretreatment with either the converting enzyme inhibitor, teprotide, or the prostaglandin synthesis inhibitor, indomethacin, failed to normalize the response to AII. Thus, neither prior receptor occupancy with endogenous AII nor the presence of vasodilatory prostaglandins caused the decreased AII response in potassium deficiency. Since the pressor response to AII involves angiotensin interaction with its vascular receptor, binding studies of mesenteric artery and uterine smooth muscle AII receptors were performed. Scatchard analysis showed that potassium deficiency resulted in a decrease in binding affinity (50% increase in Kd) in both uterine (6.00 vs. 3.82 nM; P less than 0.05) and vascular (1.39 vs. 0.973 nM; P less than 0.005) smooth muscle. Furthermore, despite increased circulating AII, there was an increase in AII receptor number in potassium-deficient uterine (308 vs. 147 fmol/mg protein; P less than 0.005) and vascular (470 vs. 316 fmol/mg protein; 0.05 less than P less than 0.1) smooth muscle. Although potassium deficiency resulted in alterations in receptor-binding parameters, the changes in binding affinity and number were directionally opposite, so that in potassium deficiency there was either no change or an increase in total AII binding. We conclude that the decrease in angiotensin pressor sensitivity in potassium-deficient rats is mediated by a postreceptor defect since it occurs subsequent to the binding of AII to its vascular smooth muscle receptor.

Angiotensin II↗
PubMed1983

Role of vasopressin in support of blood pressure in potassium deficient rats.

Arginine vasopressin (AVP) has been found to contribute to the maintenance of blood pressure (BP) in the rat. Since potassium deficiency results in alterations in systemic hemodynamics, the role of AVP in the control of BP was studied after 14 to 21 days of dietary potassium deficiency. When potassium deficient and control rats were allowed free access to water, plasma osmolality (301.4 +/- 1 vs. 293.4 +/- 3 mOsm/kg; P less than 0.02) and plasma AVP (3.5 +/- 0.2 vs. 2.4 +/- 0.2 pg/ml; P less than 0.02) were increased in potassium deficient animals. To determine the role of this increase in AVP in the maintenance of BP, BP was determined in rats made polydipsic by adding glucose to the drinking water. In both control and potassium deficient rats, increased fluid intake resulted in increased urine output, decreased urinary and plasma osmolality, and a decrease in plasma AVP. While there was no change in BP in control rats when fluid intake was increased, BP fell from 103.9 +/- 1.8 to 96 +/- 2.6 mm Hg (P less than 0.05) in potassium deficient rats with increased fluid intake. To confirm that the decrease in plasma AVP caused the decrease in BP in potassium deficient rats, an AVP pressor antagonist was employed. Following the administration of the AVP pressor antagonist, there was no change in BP in control animals. In contrast, BP fell from 104.3 +/- 1.9 to 98.3 +/- 2.5 mm Hg; P less than 0.05 in potassium deficient rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗