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The influence of plasma butyrylcholinesterase concentration on the in vitro hydrolysis of cocaine in human plasma.

In humans, the plasma enzyme butyrylcholinesterase, BChE (EC 3.1.1.8), mediates the in vivo plasma hydrolysis of cocaine to the pharmacologically inactive metabolite ecgonine methyl ester, EME. This enzyme has been purified from human plasma to investigate the potential as a treatment for cocaine intoxication. Cocaine (2.1 micrograms mL-1) was incubated in plasma with a BChE concentration in the normal range (3.02 micrograms mL-1) and in plasma with enhanced BChE concentrations of 9.14, 20.8 and 37.8 micrograms mL-1, respectively for time periods up to 120 min. Cocaine and the hydrolytic products, ecgonine methyl ester and ecgonine, were quantified simultaneously by gas chromatography-mass spectrometry (GC-MS). The enhancement of plasma BChE concentration resulted in a dramatic increase in the rate of hydrolysis of cocaine. There was a stoichimetric conversion of cocaine to the inactive hydrolysis product, ecgonine methyl ester. Accordingly, the half-life of cocaine in plasma decreased significantly with enhanced BChE concentration. At plasma BChE concentrations of 3.02, 9.14, 20.8 and 37.8 micrograms mL-1, half-life values of 116, 35.8, 21.4 and 9.0 min, respectively were observed. The marked reduction in cocaine half-life provides evidence supporting the potential therapeutic use of BChE for the treatment of cocaine intoxication.

Butyrylcholinesterase↗

Cholesterol supplementation with egg yolk increases plasma cholesterol and decreases plasma 7-dehydrocholesterol in Smith-Lemli-Opitz syndrome.

Smith-Lemli-Opitz syndrome (SLOS), an autosomal recessive condition comprising multiple malformations, mental retardation, and growth failure, results from reduced activity of the final enzyme in cholesterol biosynthesis, 7-dehydrocholesterol Delta(7)-reductase (DHCR7). Reduced plasma and tissue cholesterol concentrations and accumulation of cholesterol precursors including 7-dehydrocholesterol (7-DHC) are characteristic biochemical abnormalities. While it is still unclear what role these potentially toxic precursors have in the pathogenesis of this disorder, the accumulation of 7-DHC in the brain has been associated with impaired learning in rats and oxidized 7-DHC has been shown to induce growth retardation in cultured rat embryos. We hypothesized that supplemental dietary cholesterol would increase plasma cholesterol levels and suppress synthesis of 7-DHC and other abnormal sterols in individuals with SLOS. After baseline sterol levels were obtained, patients were provided supplemental cholesterol as egg yolk. Plasma sterols were analyzed by capillary-column gas chromatography over time in four children with SLOS. When evaluated at 4-8 weeks after the initiation of cholesterol supplementation, there was a marked increase in mean plasma cholesterol, from 53 mg/dl to 82 mg/dl. While the percent of total sterols as 7-DHC decreased from 15% to 10%, there was no change in total plasma 7-DHC levels. However, when evaluated 35-90 weeks after the institution of cholesterol supplementation, mean plasma 7-DHC decreased, from 11.3 mg/dl to 3.5 mg/dl (-67%, P < 0.05), along with an increase in mean plasma cholesterol from 53 mg/dl to 114 mg/dl (+116%, P < 0.05). These results support the hypothesis that over time dietary cholesterol supplementation from egg yolk increases the plasma cholesterol levels and decreases levels of 7-DHC which may be toxic. These data have important therapeutic implications in the management of SLOS.

Cholesterol↗

Haemonetics plasma collection system (PCS): automated collection of platelet-poor or platelet-rich plasma.

The PCS is an automated centrifugal system designed for rapid collection of platelet poor plasma (PPP) for source or fresh frozen uses, or platelet concentrate and PPP. The microprocessor-controlled system increases plasma collection efficiency through improved plasma yields, increased donor safety, and operation of multiple machines per operator. 600 ml of plasma can be collected in an average of 35 minutes per procedure with greater than 50,000 collections by U.S. commercial organizations. PCS plasma yields 10% greater Factor VIII recovery through fractionation when compared to manually-collected plasma based upon multiple studies throughout the world. Collection of PRP is an efficient, reliable, safe, and cost-effective method for processing plasma and the only system available for combined platelet and plasma procurement.

Autoanalysis↗

Self-inhibiting action of nortriptylin's antidepressive effect at high plasma levels: a randomized double-blind study controlled by plasma concentrations in patients with endogenous depression.

Below the toxic plasma level of nortriptyline (NT) an upper therapeutic limit has been postulated in patients with endogenous depression. If so the clinical significance is obvious and a double-blind, randomized study was performed in order to solve this problem. Two groups of patients were controlled at different plasma levels (less than 150 ng/ml and less than 180 ng/ml). The degree of depression was rated weekly. Only about one third (n equals 24) of the patients originally included, were carried through the full protocol, the most prominent reason for drop out beeing spontaneous remission during an initial placebo period. After 4 weeks of NT treatment the majority in the high level group was still depressed, but the difference barely significant (P equals 5.5%). However, a randomized reduction of the plasma level among the patients at the high level resulted in a significant correlation to remission. Evaluation of the total material after 6 weeks of NT treatment demonstrated a strong correlation of high plasma level to poor antidepressive effect of NT. No correlation could be obtained between side-effects, which were few, and plasma level. The non-proteinbound fraction in plasma was found to 7% (SD 1.83) by simultaneous determinations of NT in plasma and CSF in 13 patients. The variation in the proteinbinding was not likely to invalidate the over all results based on total NT determination. A therapeutic plasma range of 50-150 ng/ml is recommended.

Adult↗

Plasma renin activity and plasma catecholamines in intact and splenectomized running and swimming beagle dogs.

The influence of splenectomy in the dog on plasma catecholamine levels and plasma renin activity during treadmill running and swimming was investigated. Plasma catecholamines were measured by a radioenzymatic assay and plasma renin activity by a radioimmunoassay. Exercise consistently increased plasma catecholamine levels before and after splenectomy (range of increase:3--38 pmol X ml-1). Swimming, however, was a stronger stimulus than running. No change in the ratio between noradrenaline and adrenaline was found. In intact dogs exercise results in a marked increase in hematocrit due to splenic contraction (range of increase 3--8 volume %), while renal blood flow and plasma renin activity remain virtually constant. In splenectomized dogs, exercise has been reported to induce a decrease in renal blood flow. In contrast to this known effect on renal blood flow, splenectomy did not affect plasma renin activity in treadmill running dogs. In swimming dogs, however, plasma renin activity was increased after splenectomy (range of increase 3.3--6.9 ng X Ang I X ml-1 X h-1). Possibly, a threshold in sympathetic tone is required to increase renin release in the dog.

Animals↗

Attempts to prepare 'insulin-free plasma' from human subjects: effects of serial dilution and insulin recovery studies on immunoreactive insulin activity of partially insulin-free plasma.

The reason for attempts to prepare insulin-free plasma from human plasma is discussed. Binding agent, employed to prepare insulin-free plasma, had a capacity to bind 40% of insulin in the system. Insulin recovery from the filtrate of human standard insulin-binding agent reaction was 60%. Human plasma incubated with binding agent gave a filtrate--partially insulin-free plasma (PIFP)--which contained significantly higher amounts of insulin compared to calculated values. Insulin in PIFP was not augmented by serial dilution. Human standard insulin added to PIFP was recovered in full and the mixture was not dilution augmentable. Incubation of human plasma--human standard insulin (106 microunits/ml) mixture with binding agent gave a PIFP which had 60% of total insulin in the mixture. Dialysis did not alter the immunoreactive insulin activity of plasma. Dialysed samples showed augmentation of insulin activity on serial dilution. These observations strongly suggest the presence of a high molecular-weight, insulin-like inhibitory component in human plasma.

Antigens↗

80-year-old men have elevated plasma concentrations of catecholamines but decreased plasma renin activity and aldosterone as compared to young men.

Plasma concentrations of adrenaline, noradrenaline, aldosterone and plasma renin activity were determined in a selected group of 80-year-old men (N = 41) in good health without clinical signs of cardiovascular disease, and were compared to levels in young healthy males (N = 20, 24-28 years). Plasma adrenaline and noradrenaline concentrations were higher (0.24 median; 25th-75th percentiles 0.16-0.34 nmol/L vs 0.15; 0.11-0.18 nmol/L, p < 0.01 and 2.22; 1.58-3.27 nmol/L vs 1.15; 1.00-1.74 nmol/L, p < 0.001), and plasma renin activity and plasma aldosterone concentration were lower in the old than in the young men (0.65; 0.35-1.04 micrograms/L/1h vs 2.09; 1.23-2.41 micrograms/L/1h, p < 0.001 and 0.12; 0.09-0.19 nmol/L vs 0.38; 0.28-0.54 nmol/L, p < 0.001). In conclusion, increased plasma concentrations of catecholamines and decreased plasma concentration of aldosterone and plasma renin activity in old men, as compared to young men, must be considered when interpreting data of these hormones in elderly men.

Adult↗

Phosphatidylinositol phosphate, phosphatidylinositol bisphosphate, and the phosphoinositol sphingolipids are found in the plasma membrane and stimulate the plasma membrane H(+)-ATPase of Saccharomyces cerevisiae.

Several plasma membrane phospholipids have been studied for their ability to modulate the activity of the plasma membrane H(+)-ATPase of Saccharomyces cerevisiae. We show here that phosphatidylinositol phosphate (PIP), phosphatidylinositol bisphosphate (PIP2), and/or the phosphatidylinositol and PIP kinases are localized primarily in the plasma membrane. Previous in vivo studies with S. cerevisiae have shown that large, rapid, and reversible changes occur in the levels of PIP and PIP2 congruent with changes in cellular ATP levels. We demonstrate here that isolated plasma membranes exhibit the same changes in PIP and PIP2 content when they are supplied with or washed free of ATP. Using a mixed micellar assay we systematically studied the efficacy of the plasma membrane lipids in sustaining the activity of the plasma membrane H(+)-ATPase. We demonstrate for the first time that a number of plasma membrane glycerophospholipids effectively stimulate the ATPase, including PIP, PIP2, and cardiolipin. Phosphoinositol-containing sphingolipids, major components of the plasma membrane, are also shown to stimulate the ATPase at significantly lower levels than the glycerophospholipids and must also be considered as important effectors in vivo.

Cell Fractionation↗

Effect of dietary proteins on hepatic and plasma lipids, and some properties of major plasma lipoprotein fractions during dietary-induced hypercholesterolemia in male rats.

In order to characterize further the cholesterolemic effect of casein compared with soybean protein isolate, each of these proteins were fed to male rats at different levels of dietary cholesterol administration. An increase in the dietary cholesterol level from zero to 0.25% led to a several-fold increase in plasma triacylglycerols with a comparatively small rise in plasma cholesterol. Further increase in the cholesterol content of diet to 0.5, 1 and 2% resulted in a return of plasma triacylglycerols to normal or even subnormal values, whereas the plasma cholesterol values rose progressively. The triacylglycerolemic and cholesterolemic effects were 2-3-fold higher with casein diet than with soybean protein diet, respectively. A major part of the increased plasma cholesterol value was accounted for by cholesterol in the very-low-density lipoprotein (VLDL) fraction. Even at moderate levels (0.05-0.5%), the dietary cholesterol administration produced a series of changes in the electrophoretic pattern of plasma lipoproteins. These changes were more prominent in the rats fed casein diet, which often showed an enhanced VLDL band even on a cholesterol-free diet. An additional lipoprotein band, localized between VLDL and the LDL/HDL1 band, was observed in several rats fed casein diet with 0.05 or 0.1% cholesterol, and in rats fed soybean protein diet containing 0.25 or 0.5% cholesterol. In contrast, at the 0.25 and 0.5% levels of dietary cholesterol, plasma of casein-fed rats contained only one broad band within the VLDL-LDL/HDL1 region. All these findings indicate that casein diet promotes the appearance of one or more specific type(s) of cholesterol-induced plasma lipoprotein particles even at a comparatively low level of dietary cholesterol.

Animals↗

Seasonal variations of plasma lipids and lipoproteins in the hedgehog, an animal model for lipoprotein (a) metabolism: relation to plasma thyroxine and testosterone levels.

We describe a study of the seasonal variations of hedgehog plasma lipids and lipoproteins and their correlation with changes in the activities of the thyroid and testis. In ten male hedgehogs, plasma concentrations of lipids, thyroxine and testosterone were assayed each month for 1 year beginning in September, while plasma lipoproteins from five of these animals were analyzed at the same dates using density gradient ultracentrifugation. All classes of plasma lipids (cholesterol, total glycerol and phospholipids) exhibited statistically significant seasonal variations in their respective concentrations, with simultaneous maxima (cholesterol: 207 +/- 39 mg/100 ml; total glycerol: 50 +/- 9 mg/100 ml; phospholipids: 266 +/- 25 mg/100 ml) during late fall-early winter, i.e., during the period of the year when plasma levels of both thyroxine and testosterone were minimal. Plasma lipids subsequently decreased to minimal levels either in early summer (cholesterol: 129 +/- 18 mg/100 ml; phospholipids: 178 +/- 20 mg/100 ml) or in late winter (total glycerol: 22 +/- 9 mg/100 ml). Very low density lipoproteins (d less than 1.015 g/ml) were found at low levels (less than 15 mg/100 ml) during the cold months, and then became detectable as trace components only. The total concentration of the mixed lipoprotein population (i.e., low density lipoproteins, Lp(a), and high density lipoprotein (HDL)-like particles) in the d 1.015-1.065 g/ml interval decreased by almost 50% from January to February (from 164.3 to 89.2 mg/100 ml), i.e., following a 10-fold increase in the level of plasma testosterone, and immediately before the rapid doubling in plasma thyroxine concentration. The staining intensity of the electrophoretic band with migration characteristics corresponding to those of Lp(a) decreased considerably during winter. At the same period of the year, lower density (1.032-1.055 g/ml) HDL-like particles disappeared. The concentration of lipoproteins with d 1.065-1.162 g/ml, which included Lp(a) particles in addition to typical HDL, equally underwent seasonal variations. These variations consisted of two successive maxima in late fall (426.4 mg/100 ml) and late winter (458.3 mg/100 ml) with two subsequent decreases leading to minima in February (327.8 mg/100 ml) and August (257.1 mg/100 ml). Finally, very high density lipoproteins (d 1.162-1.259 g/ml) were heterogeneous, containing both cholesterol-rich (d 1.162-1.227 g/ml) and phospholipid-rich (d 1.194-1.259 g/ml) subpopulations.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Human liver plasma membranes contain an enzyme activity that removes membrane anchor from alkaline phosphatase and converts it to a plasma-like form.

Treatment of liver plasma membranes with Triton X-100 allowed an endogenous alkaline phosphatase-converting activity to convert amphiphilic alkaline phosphatase (membrane anchor covalently attached) to hydrophilic dimers that resemble the enzyme found in normal plasma. The Triton-solubilized activity was unaffected by protease inhibitors. Amphiphilic alkaline phosphatase purified from human liver and placenta were both substrates. The Triton-solubilized enzyme would not hydrolyze L-3-phosphatidyl(2-3H)-inositol or p-nitrophenylphosphoryl choline, nor would it cleave endogenous alkaline phosphatase from intact plasma membranes. These observations and the analysis of the protein product of the hydrolysis of placental alkaline phosphatase, following treatment with the converting activity, indicated that the enzyme has the specificity of a glycosyl-phosphatidylinositol phospholipase D. Further characterization of the enzyme activity suggests additional similarities with the glycosyl-phosphatidylinositol phospholipase D found in mammalian plasma. Alkaline phosphatase-converting activity in plasma membranes represented the same percent of total protein as it did in whole liver, whereas serum contained 3- to 10-times this amount. Endogenous converting activity in plasma membranes was not solubilized by salt washes, sonication, or repeated freeze-thaw treatments. We believe it is unlikely that the alkaline phosphatase-converting activity in liver plasma membranes resulted from adsorption of the enzyme present in plasma.

Alkaline Phosphatase↗

Plasma high density lipoproteins HDL2, HDL3 and postheparin plasma lipases in relation to parameters of physical fitness.

A number of studies has shown that the plasma levels of high density lipoprotein (HDL) are increased by regular aerobic exercise. The plasma HDL, particularly HDL2, is regulated by the activity of 2 endothelial lipases, viz. lipoprotein lipase (LPL) and hepatic lipase (HL), which both can be assayed in postheparin plasma. In the present study the plasma levels of HDL2 and HDL3 cholesterol and the postheparin plasma lipase activities were related to parameters of physical fitness obtained from a pulse conducted maximal bicycle ergometer test. There was a significant positive correlation between HDL2 cholesterol and physical fitness (r = 0.52, P less than 0.01). On the other hand, the postheparin plasma hepatic lipase activity showed a significant negative correlation to physical fitness (r = -0.57, P less than 0.01). The HDL2 cholesterol was inversely correlated with the HL activity (r = 0.57, P less than 0.001). Application of partial correlation analysis to the data showed that the relationship between HDL2 cholesterol and fitness disappeared by keeping the HL activity constant whereas the correlation between HDL2 and HL was not influenced by fitness. The relation of HDL2 to fitness was independent in body fat and basal plasma insulin level; in addition the relationship between HL and fitness was not accounted for by body fatness. No relationship was found between physical fitness and LPL activity or between HDL3 and fitness. The results support the hypothesis that hepatic endothelial lipase has a role in the regulation of plasma HDL2 cholesterol and that the activity of this enzyme decreases upon increase of physical fitness.

Adult↗

Plasma volume expansion increases lysophosphatidylcholine and digitalis-like activity in rat plasma.

A circulating factor with digitalis-like activity has been proposed to play a role in the regulation of plasma volume. Lysophosphatidylcholine has been found to be active in many assays for digitalis-like activity. To examine the relationship between plasma digitalis-like activity and plasma lysophosphatidylcholine, the effect of plasma volume expansion with saline on the plasma levels of phospholipids and on the ability of delipidated extracts of plasma to displace tritiated ouabain from the digitalis receptor was determined. Lysophosphatidylcholine was elevated after 15, 30, and 120 minutes of volume expansion but was decreased at 60 minutes. Phosphatidylcholine was decreased at 15, 60, and 120 minutes. Plasma sphingomyelin was not altered at any time point. The ability of plasma to displace tritiated ouabain was increased only at the 60 minute time point. These results indicate that the increase in digitalis-like activity in volume expanded states is mediated by a combination of at least two factors, lysophosphatidylcholine and another factor whose digitalis-like activity is not related to the surfactant actions of a lipid.

Animals↗

Postprandial plasma vitamin A metabolism in humans: a reassessment of the use of plasma retinyl esters as markers for intestinally derived chylomicrons and their remnants.

We investigated postprandial vitamin A metabolism by measuring retinyl ester, triglyceride, and apolipoprotein (apo)B-48 in the plasma lipoproteins of human subjects before and after fat-feeding. Following a 14-hour fast, eight healthy subjects (two men, six women, 28 to 79 years) were given a fat-rich meal (1 g fat/kg body weight) containing vitamin A (40 retinol equivalents per kilogram body weight). Blood was collected every 3 hours for 12 hours and lipoproteins were isolated by sequential ultracentrifugation. Mean plasma retinyl ester concentration peaked 6 hours after the fat-rich meal, whereas mean plasma triglyceride peaked at 3 hours. Data obtained from hourly samples in 3 subjects showed that changes in the postprandial plasma concentration of retinyl ester occurred 1 to 2 hours after changes in the plasma triglyceride concentration. In triglyceride-rich lipoproteins (TRL) of d less than 1.006 g/mL, retinyl ester similarly peaked at 6 hours, whereas triglyceride as well as apoB-48 peaked at 3 hours. Although retinyl esters were found mainly in TRL in the initial postprandial period (84%, 3 hours; 83%, 6 hours), in fasting and postprandial plasma, particularly 9 or more hours after fat-feeding, a large percentage of plasma retinyl esters were in low-density lipoproteins (LDL) (44%, fasting; 9%, 3 hours; 9%, 6 hours; 19%, 9 hours; 32%, 12 hours). A small percentage of retinyl esters were also found in postprandial high-density lipoproteins (HDL) (2% to 7%). ApoB-48 was not detected in LDL of fasting or postprandial plasma.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Plasma levels of lathosterol and phytosterols in relation to age, sex, anthropometric parameters, plasma lipids, and apolipoprotein E phenotype, in 160 Dutch families.

In this study, the relation of plasma levels of lathosterol (an indicator of whole body cholesterol synthesis) and plant sterols (indicator of cholesterol absorption) with age, sex, weight, height, plasma lipids, and lipoproteins, and with apolipoprotein (apo) E phenotype, was investigated in a group of 160 nuclear families consisting of twins living with their parents. Lathosterol was higher in fathers than in mothers, but not different between boys and girls. In each of these four groups, there was a strong correlation with plasma and low-density lipoprotein (LDL)-cholesterol and -triglyceride, as well as with body weight, but not with height or high-density lipoprotein (HDL)-cholesterol. In adults, lathosterol was inversely correlated with plant sterols. Lathosterol was higher in children with E4/3 phenotype than in those with E3/3 or E3/2; in adults, lathosterol did not differ among the various E phenotypes. The plasma levels of the two plant sterols, campesterol and beta-sitosterol, were highly correlated with each other, and also with plasma or LDL-cholesterol, in each of the four groups. Plant sterols were higher in adults or children with E4/3 phenotype as compared with those with other phenotypes. In multivariate analysis (performed separately for two groups of adults and children) plasma cholesterol, plasma plant sterols, plasma triglycerides, and weight were found to make significant contributions to the variation of lathosterol in all groups, and E phenotype and sex only in one group, while age did not contribute in any group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Plasma tissue factor pathway inhibitor in disseminated intravascular coagulation: comparison of its behavior with plasma tissue factor.

In order to assess the clinical implication of tissue factor pathway inhibitor (TFPI) in disseminated intravascular coagulation (DIC), plasma concentrations of TFPI were measured together with plasma tissue factor (TF) in 30 healthy subjects and 49 patients with DIC associated with a variety of underlying diseases. The mean TFPI concentration was elevated in patients with DIC at presentation (205.8 +/- SD 79.1 ng/ml) as compared with healthy subjects (97.3 +/- 22.2 ng/ml, P < 0.001). The mean plasma TF concentration in patients with DIC (412.7 +/- 445.7 pg/ml) was also higher than that in healthy subjects (137.5 +/- 50.6 pg/ml, P < 0.001). Elevated TF levels were found predominantly in patients with DIC caused by cancer and leukemia, whereas TFPI was elevated in all underlying disease categories. Plasma TFPI concentration did not correlate with plasma TF. In addition, hemostatic markers of DIC such as thrombin-antithrombin complex, prothrombin fragment 1 + 2, plasmin-plasmin inhibitor complex, FDP or fibrinogen did not correlate with TFPI. Serial determinations of plasma TFPI in each patient demonstrated that the behavior of TFPI was independent of the changes in plasma TF and other hemostatic parameters. These findings indicate that plasma TFPI does not decrease in DIC and is not valuable for monitoring the progress of DIC.

Disseminated Intravascular Coagulation↗

Surface characterization and ex vivo blood compatibility study of plasma-modified small diameter tubing: effect of sulphur dioxide and hexamethyldisiloxane plasmas.

The development of a small diameter artificial vascular graft or prosthesis is limited by rapid thrombus formation and subsequent embolization upon blood contact. Plasma surface modification was employed to modify the inner surface of small diameter low density polyethylene (LDPE) tubing without varying the outer surface chemistry and physical properties of the tubing. A sulphur dioxide (SO2) plasma was used to form sulphonate functionality on the surface. In addition, a hexamethyldisiloxane (HMDSO) plasma and different gas flow ratios of SO2-HMDSO gas mixture plasmas were used to form ultrathin polysiloxane-like coatings inside the LDPE tubing. X-ray photoelectron spectroscopy (XPS) indicated that the inner surface of the tubing can be modified uniformly with this treatment. In addition, XPS results showed that the percentage of sulphur atoms bound to two or three oxygen atoms (sulphone or sulphonate) increased with the SO2-HMDSO mass flow rate ratio. The blood compatibility of the plasma-modified model materials was evaluated using an ex vivo canine arteriovenous shunt model. Similar thrombogenicity was observed comparing the untreated control and the surfaces modified by HMDSO plasma and SO2-HMDSO gas mixture plasmas, despite the differences in surface chemistry. The SO2 plasma-modified surface, which is the most hydrophilic as measured by the captive bubble contact angle measurement technique, was more thrombogenic than the untreated control. This may be attributed to the combined effect of the surface chemistry and surface hydrophilicity.

Animals↗

Changes in plasma catecholamines and plasma renin activity during hypotension in conscious rats with lesions of the nucleus tractus solitarii.

The purpose of the present study was to examine the effects of lesions of the nucleus tractus solitarii on the reflex control of sympathetic activity and renin release in the conscious rat. Two doses of the arteriolar vasodilator hydralazine (0.3 and 1 mg/kg, i.v.) were used to activate reflexively the sympathetic nervous system in nucleus tractus solitarii lesion and control rats. Administration of 1 mg/kg of hydralazine to the control rats caused mean arterial pressure to fall from 120 +/- 2 mm Hg to 84 +/- 2 mm Hg and elicited an 11.2-fold increase in plasma renin activity and a 2.7-fold increase in plasma norepinephrine concentration. Administration of 0.3 mg/kg of hydralazine caused the arterial pressure of the lesion group to fall from 118 +/- 3 mm Hg to a comparable value of 85 +/- 4 mmg Hg, but plasma renin activity and plasma norepinephrine concentration did not rise significantly. However, administration of 1 mg/kg of hydralazine to the lesion group caused arterial pressure to fall from 128 +/- 6 mm Hg to 64 +/- 2 mm Hg, in association with a 12.4-fold increase in plasma renin activity and a 1.6-fold elevation in plasma norepinephrine concentration. Atenolol, a beta 1-adrenoceptor antagonist, blocked 70% of the rise in plasma renin activity caused by 1 mg/kg of hydralazine in both groups of rats. In addition, prior renal denervation also markedly attenuated the rise in plasma renin activity caused by hydralazine in the lesion group. Finally, electrical stimulation of the vagus nerves, which caused a large vasodepressor response in the control group, failed to lower the arterial pressure of the lesion group. Based on these observations, we conclude that in the conscious rat (1) nucleus tractus solitarii lesions eliminate the arterial baroreflexes as well as the cardiopulmonary baroreflex, and (2) severe hypotension induces sympathetically mediated renin release in the apparent absence of arterial and cardiopulmonary baroreflex function.

Animals↗