摘要:

Recent work suggests that oxygen radicals may be important mediators of damage in a wide variety of pathologic conditions. In this review we consider the evidence supporting the participation of oxygen radicals in the adult respiratory distress syndrome, in ischemia reperfusion injury in the myocardium, and in cerebral vascular injury in acute hypertension and traumatic brain injury. In the adult respiratory distress syndrome there is active sequestration of polymorphonuclear neutrophils in the pulmonary vascular system. There is evidence that activation of these neutrophils results in the production of oxygen radicals which injure the capillary membrane and increase permeability, leading to progressive hypoxia and decreased lung compliance which are hallmarks of the syndrome. In acute arterial hypertension or experimental brain injury oxygen radicals are important mediators of vascular damage. The metabolism of arachidonic acid is the source of oxygen free radical production in these conditions, in myocardial ischemia and reperfusion injury, the ischemic myocyte is "primed" for free radical production. With reperfusion and reintroduction of molecular oxygen there is a burst of oxygen radical production resulting in extensive tissue destruction. Myocardial ischemia–reperfusion injury shares in common with the other two syndromes activation of the arachidonic acid cascade and acute inflammation. Thus it would appear that the generation of toxic oxyoen species may represent a final common pathway of tissue destruction in several pathophysiologic states.

ISSN:0008-4212    

DOI:10.1139/y85-034

出版商:NRC Research Press    

年代:1985

数据来源: NRC

摘要:

We measured, in 11 healthy volunteers, the contributions of rib cage and abdomen–diaphragm compartments to increased ventilation caused by hypercapnia, hypoxia, and exercise to determine whether different stimuli produce similar or different patterns of ventilation with respect to the motion of rib cage and abdominal compartments. Progressive hypcroxic hypercapnia and progressive isocapnic hypoxia were induced by rebreathing methods and graded exercise performed on a treadmill, and compartmental tidal volume (VT) was measured by respiratory inductive plethysmography. For each stimulus, the wide range ofVTresponses among individuals was determined primarily by the range of rib cage contributions toVT, the abdominal compartmentVTresponse slopes accounting for less of this range. There were no significant differences between hypercapnia and hypoxia in either rib cage or abdominal contributions to ventilation (for both,p < 0.3). However, exercise rib cage and abdominal contributions to ventilation were significantly different from those during chemically driven breathing: for the rib cage compartment,p < 0.0001 and for the abdominal compartment,p < 0.05. Whereas, in 8 of 10 subjects the rib cage contribution toVTduring exercise was similar to or exceeded that during rebreathing, in 7 of 10 subjects the abdomen–diaphragm contribution fell below that measured during both hypercapnia and hypoxia. There was a significant correlation between hypercapnia and hypoxia in theVTcontribution of each compartment at equivalent levels of ventilation (rib cage,p < 0.0001; abdomen,p < 0.0005), but there was no significant correlation in theVTcontribution of either compartment between exercise and hypercapnia or exercise and hypoxia. The pattern of compartmental contributions to ventilation during treadmill exercise differs significantly from that observed during chemically driven breathing.

ISSN:0008-4212    

DOI:10.1139/y85-035

出版商:NRC Research Press    

年代:1985

数据来源: NRC

摘要:

The Ca2+channel antagonists D-600, diltiazem, and nifedipine are competitive antagonists of Ca2+responses in K+-depolarized guinea pig taenia coli and rat mesenteric artery preparations. pA2values for D-600, diltiazem, and nifedipine in taenia coli were 8.28, 7.44, and 9.27, respectively and in mesenteric artery, 9.6, 7.83, and 10.4, respectively. The combination of nifedipine plus diltiazem gave in both tissues antagonism greater than that calculated on the basis of additivity. This suggests, consistent with published3H-Sabelled radioligand binding data, that diltiazem and nifedipine interact at distinct sites. However, the combination nifedipine plus D-600 yielded antagonism consistent with additivity of response.

ISSN:0008-4212    

DOI:10.1139/y85-036

出版商:NRC Research Press    

年代:1985

数据来源: NRC

摘要:

Vanadium (V) as sodium orthovanadate induces an increase in lipid peroxidation in the kidneys after a single subcutaneous or intraperitoneal injection to rats or mice. The rate of malondialdehyde (MDA) formation, an index of lipid peroxidation, by-kidney homogenates increased by more than 100% 1 h after injection. Chronic exposure of rats to vanadium sulfate, initially through maternal milk and later in the drinking water, resulted after 10 weeks in a significant increase in MDA formation by kidney but not by other tissues, in both acute and chronic studies in rats and mice, no significant increase in lipid peroxidation by V treatment was detected in brain, heart, lung, spleen, or liver. In mice, administration of ascorbate prior to acute exposure to V diminished both toxicity, i.e., respiratory depression and limb paralysis, and the formation of MDA in kidney.

ISSN:0008-4212    

DOI:10.1139/y85-037

出版商:NRC Research Press    

年代:1985

数据来源: NRC

摘要:

Binding of (−)-[3H]quinuclidinyl benzilate (QNB) to muscarinie sites in guinea-pig atrial and ileal longitudinal muscle homogenates showed the presence of a single population of binding sites in atria (KD = 41 (32–53) (95% confidence limits) pM;Bmax = 0.225 ± 0.02 pmol/mg protein (3)) and two binding sites in the ileum (KD = 20.9 (8.8–49) pMand 11.3 nM;Bmax = 0.436 ± 0.09 and 11.85 ± 2.63 pmol/mg protein (4), respectively). Atropine, gallamine, and pancuronium displaced (−)-[3H]QNB binding from the high affinity binding sites in the two tissues in a dose-dependent manner with –logKivalues of 8.6, 6.4, and 6.9, respectively, in atria and 8.7, 6.8, and 6.9, respectively, in ileal longitudinal muscle. The lack of selectivity of gallamine and pancuronium in binding experiments differed from results obtained in isolated tissue experiments where these antagonists showed a marked difference in their ability to antagonize cholinomimetics in the two tissues. In addition, theKivalues for gallamine and pancuronium in ileal homogenates wereca. 130- and 16-fold lower, respectively, than theirKBvalues determined from isolated tissue experiments. Attempts to correlate data from binding experiments and isolated tissue experiments using combinations of antagonists led to variable results attributed to differences in the rates of dissociation of the antagonists from muscarinic receptors. It is concluded that the interaction of gallamine or pancuronium with agonists or antagonists at muscarinic receptors is not a simple bimolecular interaction.

ISSN:0008-4212    

DOI:10.1139/y85-038

出版商:NRC Research Press    

年代:1985

数据来源: NRC

摘要:

Alterations of smooth muscle function can just as easily stem from mechanical alterations in its ability to relax as from alteration in contraction. Since a failure of arterial smooth muscle to relax may contribute to the development of hypertension, we felt it necessary to study the relaxation process in greater depth. The effect of load on the time course of relaxation of rat caudal artery smooth muscle was analyzed either by comparing afterloaded contractions against various loads or by imposing abrupt alterations in load. Unlike mammalian striated muscles in which relaxation was reported sensitive to loading conditions, relaxation in the smooth muscle of the rat caudal artery (n = 17) was found to be largely independent of loading conditions. This type of relaxation has been termed "inactivation-dependent" relaxation; it is typical of muscle tissue in which the calcium sequestering apparatus is poorly developed. Our results suggest that calcium resequestration, or some biochemical process downstream to it, is the rate-limiting step during relaxation in arterial smooth muscle and that this is not qualitatively different for hypertensive arterial smooth muscle. These analytic techniques were used in the study of relaxation of hypertensive vessels. Quantitative analysis of the relaxation curves showed that both isometric and isotonic relaxation time was prolonged in hypertensive arterial smooth muscle. Prolonged isotonic relaxation indicates that hypertensive arteries remain narrowed for prolonged periods compared with normotensive vessels. Such narrowed vessels may be a factor in the increased total peripheral resistance seen in genetic hypertension.

ISSN:0008-4212    

DOI:10.1139/y85-039

出版商:NRC Research Press    

年代:1985

数据来源: NRC

摘要:

Two types of cytoplasmic 17 β-estradiol (E2) binding activity were identified and characterized in the uteri of pregnant, cycling and prepubertal, cycle-induced (400 IU pregnant mare's serum gonadotrophin (PMS) + 200 IU human chorionic gonadotropin (hCG)) gilts. Overall, type I affinity and capacity wereKd1.94 ± 0.51 nMand 5.410 ± 1.09 pmol/mg protein, respectively; type II apparent dissociation constant and capacity wereKd21.34 ± 6.83 nMand 62.58 ± 15.96 pmol/mg protein, respectively. Cytoplasmic luteal E2receptors were undetectable in all groups. Uterine E2receptor activity was eluted from diethylaminoethyl columns by a 0.05–0.15 MKCl gradient. Sodium dodecyl sulfate polyacrylamide gel electrophoresis indicated a molecular weight of 70 400–79 000. Excluding gilts with cystic ovarian follicles (16.67%), prepubertal gilts treated with PMS + hCG versus cycling sows had lower serum progesterone on days 6 and 9–13 of the estrous cycle and lower 13,14-dihydro-15-keto prostaglandin F2αlevels on days 0–9 and 13–17 of the cycle. Implants, containing 200 mg estrone inserted subcutaneously on days 12–19 after PMS + hCG treatment in gilts, had no discernible effects on these parameters. These results indicate that the diminished reproductive capacity of the gilt, in which cycle activity is induced by PMS + hCG, is likely due to decreased luteal progesterone secretion. Preliminary data also suggest that the lack of E2receptors may contribute to the low reproductive performance in gilts with cystic ovarian follicles.

ISSN:0008-4212    

DOI:10.1139/y85-040

出版商:NRC Research Press    

年代:1985

数据来源: NRC

摘要:

The effect of converting enzyme inhibitor (CEI) on the renal response to atrial natriuretic factor (ANF) was determined in the rat. In the absence of CEI, ANF produced rapid and significant increases in sodium, potassium, calcium, and urine excretions while blood pressure declined transiently. In the presence of CEI, ANF enhanced the excretion of sodium and potassium but not of calcium and urine. The activity of CEI was documented by observing that, in the presence of CEI, the elevation of blood pressure produced by angiotensin I was significantly attenuated. The potentiating effect of CEI on the natriuretic response to ANF supports the hypothesis that converting enzyme may be involved in the metabolism of ANF.

ISSN:0008-4212    

DOI:10.1139/y85-041

出版商:NRC Research Press    

年代:1985

数据来源: NRC

摘要:

In chloralose-anaesthetized dogs, plasma vasopressin concentration was measured by radioimmunoassay during step changes in blood volume of 4 mL/kg over a range of blood volume from +20 to −12 mL/kg. Blood volume was both increased and decreased over this range. There was a logarithmic relationship between blood volume and plasma vasopressin concentration over the range of blood volume examined. There was also a logarithmic relationship between blood volume and mean left atrial pressure. Linear regression between the natural logarithm of plasma vasopressin concentration and mean arterial pressure, heart rate, and mean left atrial pressure gave the highest correlation coefficient (r = 0.94) between vasopressin and mean arterial pressure. The results support the hypothesis that there are sensitive mechanisms controlling the release of vasopressin in response to changes in blood volume. Observations were also made of changes in atrial pressure and activity of left atrial receptors during changes in blood volume over the same range. The results suggest that changes in atrial receptor activity are unlikely to be the major cause of the large increases in plasma vasopressin concentration associated with hypovolemia.

ISSN:0008-4212    

DOI:10.1139/y85-042

出版商:NRC Research Press    

年代:1985

数据来源: NRC

摘要:

The pressure at zero flow was examined using three independent techniques in island epigastric skin flaps in dogs under sodium pentobarbital anesthesia. (i) The flap was perfused from a reservoir which was varied in height to supply a range of pressures. The corresponding flows were measured by electromagnetic blood flowmetry and the pressure at zero flow was determined by extrapolation to zero flow. (ii) Arterial inflows as low as 2.2 μL/min were delivered by a Harvard pump and corresponding pressures were measured. The pressure at zero flow was determined by inspection. (iii) The artery supplying the flap was occluded with a microclip and the plateau following the decay of pressure was read as the pressure at zero flow. The pressure decay technique was the simplest, most reproducible method and was verified by the other two methods. It gave a pressure at zero flow of 5.8 ± 0.4 mmHg (0.77 ± 0.05 kPa). The critical closing pressure is discussed and related to the pressure at zero flow.

ISSN:0008-4212    

DOI:10.1139/y85-043

出版商:NRC Research Press    

年代:1985

数据来源: NRC