Magnitude Of Relaxation Research Articles

Intersystem crossing rate constants from the (0,4,1) and (1,2,1) levels of the à 1A2 to ã 3B1 state of SO2

Collision-induced intersystem crossing rate constants from the (0,4,1) and (1,2,1) levels of the à 1A2 to ã 3B1 state and rovibronic relaxation rate constants in the à 1A2 state of SO2 have been studied. The laser wavelength was set at 335.86 and 334.09 nm for the (0,4,1) and (1,2,1) excitation, respectively. When a few rotational levels belonging to the (0,4,1) and (1,2,1) vibrational levels were populated by a narrow bandwidth laser, both the fluorescence from the à 1A2 state and the phosphorescence from the ã 3B1 state were observed from the time resolved emission spectra. The decay behavior of the fluorescence signal showed fast and slow components. The radiative lifetimes and apparent quenching rate constants obtained from the fast component analysis are 38±5 and (9.8±0.2)×10−10 for (0,4,1) excitation and 33±5 μs and (1.0±0.1)×10−9 cm3 mol−1 s−1 for (1,2,1) excitation, respectively. The effective lifetimes and quenching rate constants for the slow component are 280±100 and (1.5±0.1)×10−10 for (0,4,1) excitation and they are 220±100 μs and (1.6±0.1)×10−10 cm3 mol−1 s−1 for (1,2,1) excitation. Based on the measured rate constants, kinetic simulations of the emission profiles were done to obtain the magnitudes of intersystem crossing and rovibronic relaxation rate constants. The magnitudes of the rovibronic relaxation and the intersystem crossing rate constants are found to be in the range of 8.5–10.0×10−10 and 1.3–1.5×10−10 cm3 mol−1 s−1, respectively.

Effect of Stress Concentration on Tensile Fracture Behavior of Carbon-Carbon Composites

The effect of stress concentrations on tensile fracture behavior of carbon-carbon (C/C) composites was investigated using circularly holed specimens and double-edge-notched (DEN) specimens. As for the circularly holed specimens, the tensile fracture stress was much higher than that estimated from the maximum stress criterion, which suggest that major stress relaxation mechanisms should exist. On the other hand, the linear elastic fracture mechanics can be applied to the DEN specimen, which means the damaged zone should be small enough compared with the notch length. In order to discuss the magnitude of the stress relaxation, damaged regions of the two kinds of testing geometry were estimated using the point stress criterion. The estimation led to remarkable difference in the size of the damaged regions, which will explain the difference in the magnitude of the stress relaxation. Through the observations of fractured specimen, it was deduced that not only the shear deformation but delamination along fiber bundles and opening of transverse crack would relax the stress concentrations. The other mechanism was also proposed based on the testing results, that is strength increase in the damaged region.

Chronic treatment with losartan ameliorates vascular dysfunction induced by aging in spontaneously hypertensive rats.

To evaluate the effects of prolonged treatment with losartan on endothelium-dependent and endothelium-independent relaxations of aortic rings from adult and senescent spontaneously hypertensive rats, and to clarify whether these effects were due to specific mechanisms of the drug or a consequence of its blood-pressure-lowering action. Adult (aged 5 months) and senescent (aged 20 months) male spontaneously hypertensive rats were treated for 12 consecutive weeks with 10 mg/kg per day losartan. Systolic blood pressure and plasma concentration of nitrates were evaluated. We studied endothelium-dependent and endothelium-independent relaxations and response to angiotensin II of aortic rings from rats of each group. The direct effects of angiotensin II type 1 receptor antagonism on vascular reactivity of aortic rings from untreated adult and senescent rats that had been incubated beforehand with losartan were also studied. Losartan treatment comparably reduced blood pressure and increased plasma concentration of nitrates in rats of both age groups. Responses to acetylcholine and sodium nitroprusside were lower for rings from senescent than they were for rings from adult rats. Constrictor responses to angiotensin II were higher for rings from senescent than they were for rings from adult rats. Treatment with losartan increased the magnitude of relaxations in response to acetylcholine for rings from rats in both groups, but increased the magnitude of relaxations in response to nitroprusside only for rings from senescent spontaneously hypertensive rats. Incubation beforehand of aortic rings from untreated rats with losartan enhanced magnitude of relaxations in response both to acetylcholine and to nitroprusside only for rings from senescent spontaneously hypertensive rats. The consequences of aging for endothelium-dependent and endothelium-independent relaxations of rings from spontaneously hypertensive rats are ameliorated by losartan treatment, suggesting that angiotensin II plays a role via type 1 receptors. The effects of losartan on senescent spontaneously hypertensive rats were due not only to its blood-pressure-lowering action but also to the blockade of specific mechanisms derived from angiotensin II type 1 receptor antagonism, which might involve an increase in availability of NO.

Does potassium induce the release of nitric oxide in the rabbit corpus cavernosum?

We investigated the effects of increases in the extracellular potassium concentration on the function of the rabbit corpus cavernosum. The resting tissue tension increased as the potassium concentration was increased from 4.7 mM to 20 mM or 30 mM. The maximum contraction induced by 200 microM phenylephrine was significantly decreased in the presence of 30 mM potassium compared with 4.7 mM potassium. After precontraction was induced with 200 microM phenylephrine, the magnitude of field-stimulated relaxation increased significantly as the potassium concentration was increased from 4.7 mM to 10 or 20 mM, but was almost completely abolished at 30 mM potassium. There was no difference in the suppressive effect of L-NAME on field-stimulated relaxation between specimens treated with 4.7 mM or 20 mM potassium. ATP- and bethanechol-induced relaxation was not affected by increases in the extracellular potassium concentration. A high-dose potassium solution (124 mM) induced contraction of the corpus cavernosum. In tissue precontracted with phenylephrine, a high-dose potassium solution that contained phenylephrine induced relaxation of corpus cavernosum; this relaxation was completely suppressed by L-NAME. These findings suggest that small increases in the extracellular potassium concentration increase field-stimulated relaxation of the corpus cavernosum and that this relaxation is not related to the effects of nitric oxide. Relaxation induced by high-dose potassium in tissue precontracted with phenylephrine is probably the result of release of nitric oxide.

Comparison of Relaxations Evoked by Photoactivation of NO-Containing Compounds and Nitrergic Nerve Stimulation in 5-Hydroxytryptamine- and Potassium-Contracted Rat Gastric Fundus

1. The aim of the present study was to further investigate our earlier proposal of liberation of nitric oxide (NO) by photoactivation of molecules containing NO or NO 2, which in turn relaxes gastric smooth muscle, and to determine whether presynaptic- and/or postsynaptic NO-mediated relaxation is affected differently by the degree of membrane depolarization in rat gastric fundus smooth muscle. 2. During contraction of rat gastric fundus with 5-hydroxytryptamine (5-HT, 10 μM), low (K +, 25 mM) and high potassium (K +, 65.4 mM), relaxation responses to nitrergic nerve stimulation, photoactivation of caged NO compounds (streptozotocin [STZ], N ω-nitro- L-arginine-methylacetate [ L-NAME], N ω-nitro- D-arginine-methylacetate [ D-NAME]), and sodium nitroprusside (SNP) were compared. 3. Nitrergic nerve (presynaptic) stimulation and photoactivation (postsynaptic) of all caged NO compounds produced rapid, transient and reversible relaxation of 5-HT and low-K +-contracted tissues. However, when contractions were induced by high K +, the relaxation induced by nerve stimulation was abolished, whereas relaxations induced by photoactivated NO compounds were significantly ( P<0.01) reduced. 4. The relaxation induced by sodium nitroprusside (SNP), but not papaverine, was also diminished in high-K +-contracted tissues. The magnitude of photoactivated NO-induced relaxation was related to the amount of NO release, light intensity and concentration of compounds. 5. The evidence that photoactivated NO-induced relaxation is mediated by cGMP comes from the observation that zaprinast, but not forskolin, potentiated the relaxation. 6. It is concluded that rat gastric smooth muscle relaxes to photoactivation of NO or NO 2-carrying molecules via NO, and it appears that degree of membrane depolarization may be a critical factor in dissociating the response to presynaptic- and postsynaptic NO-mediated relaxation in this muscle.

Involvement of the cytoskeleton in calcium-dependent stress relaxation of rat aortic smooth muscle.

Rat aortic smooth muscle exhibits a remarkable capacity for stress relaxation, the release of tension following tissue stretch. Stress relaxation was markedly enhanced in contracted aortic rings compared with unstimulated tissue. The magnitude of stress relaxation in contracted aortic rings correlated well with the passive tension imposed on the tissue by stretching, but showed little relationship to changes in tissue length or to the level of tension developed in response to agonist stimulation prior to stretch. The enhancement of stress relaxation in precontracted tissue was not affected by intimal rubbing or treatment with L-NAME. By comparison, the removal of extracellular calcium markedly attenuated stress relaxation. In addition, the use of cytochalasin B to block actin polymerization inhibited stress relaxation, whereas colchicine, a drug used to cause microtubule disassembly, had no effect on the phenomenon. The results indicate that the enhanced stress relaxation in contracted tissue is a calcium-dependent process and is not due to passive tissue elastic properties. We suggest that stress relaxation may not involve cross-bridge formation but could be explained by the remodelling of a portion of the tension-bearing actin cytoskeleton.

Oesophageal tone in patients with achalasia

Background—The diagnosis and classification of oesophageal motility disorders is currently based on assessment of the phasic contractile activity of the oesophagus. Tonic muscular contraction of the oesophageal body (oesophageal tone)...

Potentiation of endothelium-dependent relaxation by epoxyeicosatrienoic acids.

Epoxyeicosatrienoic acids (EETs) are potent endothelium-derived vasodilators formed from cytochrome P-450 metabolism of arachidonic acid. EETs and their diol products (DHETs) are also avidly taken up by endothelial cells and incorporated into phospholipids that participate in signal transduction. To investigate the possible functional significance of EET and DHET incorporation into cell lipids, we examined the capacity of EETs and DHETs to relax porcine coronary arterial rings and determined responses to bradykinin (which potently activates endothelial phospholipases) before and after incubating the rings with these eicosanoids. 14,15-EET and 11,12-EET (5 mumol/L) produced 75 +/- 9% and 52 +/- 4% relaxation, respectively, of U46619-contracted rings, whereas 8,9-EET and 5,6-EET did not produce significant relaxation. The corresponding DHET regioisomers produced comparable relaxation responses. Preincubation with 14,15-EET, 11,12-EET, 14,15-DHET, and 11,12-DHET augmented the magnitude and duration of bradykinin-induced relaxation, whereas endothelium-independent relaxations to aprikalim and sodium nitroprusside were not potentiated. Pretreatment with 2 mumol/L triacsin C (an inhibitor of acyl coenzyme A synthases) inhibited [3H]14,15-EET incorporation into endothelial phospholipids and blocked 11,12-EET- and 14,15-DHET-induced potentiation of relaxation to bradykinin. Exposure of [3H]14,15-EET-labeled endothelial cells to the Ca2+ ionophore A23187 (2 mumol/L) resulted in a 4-fold increased release of EET and DHET into the medium. We conclude that incorporation of EETs and DHETs into cell lipids results in potentiation of bradykinin-induced relaxation in porcine coronary arteries, providing the first evidence that incorporated EETs and DHETs are capable of modulating vascular function.

Developmental dynamics of endothelial and neurogenic control of canine thoracic aorta

The purpose of the study was to confront the range of endothelial relaxation and neurogenic contraction of the thoracic aorta in fetuses (1 week before birth), puppies (1, 2, 4 and 6 weeks old), and in adult dogs. Isometric tension of aortic rings was monitored in organ bath. Acetylcholine-induced dose-dependent relaxation of aortic rings precontracted by phenylephrine was pronounced already in fetuses and puppies and significantly larger than in adults. Indomethacin, a cyclooxygenase inhibitor, did not affect the magnitude of aortic relaxation to acetylcholine. Transmural nerve stimulation induced but very slight contractions of the thoracic aorta in fetuses, while in puppies the extent of contractions was increasing with increasing age, reaching its maximum in adults. Contractile responses of aortic rings induced by KCl were fully detectable in fetuses and puppies and increased with increasing age of the animals. Thus in ontogenesis, the extent of endothelium-dependent relaxation and neurogenic contraction of the thoracic aorta displayed an opposite trend. The acetylcholine-induced relaxation was fully operative already in fetuses and puppies and its extent was declining toward adulthood, whereas the neurogenic contraction was hardly detectable in fetuses, increasing in puppies, and showed the highest values in adults.

RELAXATION TO INTRALUMINAL AND EXTRALUMINAL FUROSEMIDE IN NEWBORN MOUSE TRACHEA. • 1519

Furosemide has been given as a bronchodilator by nebulization for direct application to the airways in an attempt to localize its actions and minimize systemic effects. It is also given by systemic administration in the treatment of infants with chronic lung disease. Although clinical studies demonstrate variable results, furosemide relaxes airway smooth muscle in vitro, using isometric tension measurement. A disadvantage of this technique is that in this system, tissues are stretched in a two dimensional fashion. Therefore, we used a cannulated, perfused video micrometry system to determine if the way in which furosemide reaches the airway, by epithelial deposition or by systemic absorption, affects the amount of relaxation. Trachea (600-800 μ diameter) from newborn mice (2-4 d), C57BL/6J and AJ strains, were cannulated and mounted onto a video micrometry system (Living Systems, Burlington, VT). Tissues were bathed in and perfused with HEPES buffer, pH 7.4 at 37°C, bubbled with 100% O2. After an equilibration period, the airways were preconstricted with extraluminal 10 μM Acetylcholine. When stable tension was achieved, 300 μM furosemide was added either extraluminally or intraluminally. Effects of extraluminal and intraluminal furosemide were compared (% change in airway diameter relative to Acetylcholine preconstriction). Relaxation to furosemide given intraluminally (65 ± 9%), with direct epithelial exposure, was not different from relaxation of extraluminally (52 ± 11%) exposed airway (p = 0.4, n=7). Thus the route of furosemide administration did not change the magnitude of relaxation when the same concentration was present either intra- or extraluminally, indicating that furosemide mediated airway relaxation is non-epithelial dependent. Further, systemically administered furosemide may produce airway relaxation if adequate concentrations reach the airway. Preliminary data herein suggest that this cannulated, perfused system may allow for a more physiologic response of the intact airway and may allow for the differentiation of epithelially mediated responses. Funding: NIH-HL45220, Leahi Trust, & US Army HSC.

Contraction and relaxation responses of femoral artery and aorta to norepinephrine in young rats

1. 1. In femoral artery of 3-week-old rats, norepinephrine (NE) at 1 nM-0.1 μM concentration-dependently produced a contraction but, at higher concentrations (0.3–30 μM), NE relaxed the tissue. 2. 2. In aorta of the 3-week-old rat, NE elicited a contraction at 1 nM to 0.3 μM and a relaxation at 1 μM and higher. 3. 3. The magnitude of the NE-induced relaxation in the aorta was much less than that in the femoral artery. 4. 4. Atenolol (a β 1-selective antagonist) modulated these NE responses in the femoral artery and butoxamine (a β 2-selective antagonist) in the aorta. 5. 5. Subcutaneous application of propranolol and isoproterenol for 10 days in 4-week-old rats sensitized and desensitized the NE-induced relaxation, respectively. 6. 6. It is suggested that, in the young rat, β 1-and β 2-adrenoceptors contribute the NE-induced relaxation in the femoral artery and aorta, respectively, and that β-adrenoceptors may contribute to the limitation of NE-induced vasoconstriction in certain types of vascular beds.

Study on the β relaxation mechanism of thermosetting polyimide/thermoplastic polyimide blends

The thermosetting polyimide PMR-15 and its blends with thermoplastic polyimides have been studied by dynamic mechanical analysis. The results obtained indicate that the level of β relaxations in PMR-15 are increased with an increase in cross-linking density. This phenomenon is interpreted as a change of chemical structure during the cross-linking process. Addition of thermoplastic polyimide makes the magnitude of β relaxations increase when PMR-15 is the major component. This might be due to the strong intermolecular charge-transfer interaction between PI and PI or PMR-15 and PMR-15 molecular chains being partly replaced by the weak intermolecular interaction between PI and PMR-15 in PMR-15/PI blends, resulting in some phenylene rings or imide groups in PIs and PMR-15 chains being able to participate in β relaxation. However, this increment in β relaxation magnitude can be reduced by heat treatment of the sample, as a result of phase separation. Hence, it is concluded that the β relaxation magnitude is determined by the number of groups which can participate in relaxation per unit length, i.e. the magnitude of β relaxation increases with decreasing interaction between the molecular chains.

Effect of morphine and naloxone on motor response of the human esophagus to swallowing and distension.

The effect of morphine on esophageal motility has been little explored. In eight healthy volunteers, we studied the effect of intravenous morphine (100 micrograms/kg) followed 60 min later by intravenous naloxone (80 micrograms/kg) and of intravenous naloxone alone (80 micrograms/kg) on the esophageal motor response to swallowing and 30-s intraluminal distensions(4, 6, 8, and 10 ml) during two separate experiments. Morphine increased (P < 0.01) the velocity but did not alter the amplitude or duration of primary peristalsis, and it decreased the duration and magnitude of swallow-induced lower esophageal sphincter (LES) relaxation (P < 0.01). It also markedly increased contractile activity below the balloon at high distending volumes (P < 0.05) and decreased the magnitude of distension-induced LES relaxation (P < 0.05) but did not affect contractile activity above the balloon. All effects were reversed by naloxone. The latter alone did not influence the esophageal response to swallowing or distension. The conclusions are that 1) morphine exerts effects on the response of the human esophagus to swallowing and intraluminal distension that are consistent with an action at the level of the inhibitory neural pathways, 2) these effects occur through opioid receptors, and 3) endogenous opioids do not seem to control esophageal motility, at least through mu-receptors.

Carbon monoxide-induced relaxation of the ductus arteriosus in the lamb: evidence against the prime role of guanylyl cyclase.

1. We have previously found that carbon monoxide (CO) potently relaxes the lamb ductus arteriosus and have ascribed this response to inhibition of a cytochrome P450-based mono-oxygenase reaction which sustains contractile tone. Our proposal, however, has been questioned on the evidence of findings in other blood vessels implicating the guanylyl cyclase-based relaxing mechanism as the target for CO. To investigate this issue further, we have carried out experiments in the isolated ductus from near-term foetal lambs and have examined the effect of CO concomitantly on muscle tone and cyclic GMP content, both in the absence and presence of guanylyl inhibitors, or during exposure to monochromatic light at 450 nm. 2. CO (65 microM) reversed completely, or nearly completely, the tone developed by the vessel in the presence of oxygen (30%) and indomethacin (2.8 microM). Cyclic GMP content tended to increase with the relaxation, but the change did not reach significance. Sodium nitroprusside (SNP), a NO donor, mimicked CO in relaxing the ductus. Contrary to CO, however, SNP caused a marked accumulation of cyclic GMP with levels being positively correlated with the relaxation. 3. Methylene blue (10 microM) reduced marginally the CO relaxation, whilst LY-83583 (10 microM) had an obvious, albeit variable, inhibitory effect. Basal cyclic GMP content was lower in tissues treated with either compound and rose upon exposure to CO. However, the levels attained were still within the range of values for tissues prior to any treatment. Furthermore, the elevation in cyclic GMP was not related to the magnitude of the CO relaxation. 4. Illumination of the ductus with monochromatic light at 450 nm reversed the CO relaxation and any concomitant increase in cyclic GMP. In the absence of CO, light by itself had no effect. 5. Ductal preparation with only muscle behaved as the intact preparations in reacting to CO, both in the absence and presence of guanylyl cyclase inhibitors, or during illumination. 6. We conclude that the primary action of CO in the ductus arteriosus is not exerted on the guanylyl cyclase heme and that cyclic GMP may only have an accessory role in the relaxation to this agent. This finding reasserts the importance of a cytochrom P450-based mono-oxygenase reaction for generation of tone and as a target for CO in the ductus.

Cycle Length Dynamics and Spatial Stability at the Onset of Postinfarction Monomorphic Ventricular Tachycardias Induced in Patients and Canine Preparations

The aim of this study was to determine whether cycle length (CL) variations at the onset of monomorphic ventricular tachycardias follow distinctive patterns. We retrospectively analyzed 59 monomorphic ventricular tachycardias induced in 40 patients in whom intraoperative mapping was performed with 63 epicardial and 64 endocardial electrograms recorded simultaneously. Activation times and CL were determined at each electrode site over several beats (36+/-10 beats, mean+/-SD) starting with the first after programmed stimulation. In the majority of the tachycardias, CL variations were accounted for by fitting to an exponential function: CL=CLs+Ae-b/tau, where CLs is the stable CL, b is beat number, tau is the time constant (in beat number), and A is the magnitude of CL relaxation. A decelerating trend (with reference to rate) (negative A) accounted for 21 tachycardias, an accelerating trend in rate (positive A) accounted for 12 tachycardias, and 4 others displayed a double dynamic behavior, with an initial acceleration followed by a decelerating trend in rate. Among the ventricular tachycardias that were not fitted to exponential models, 12 showed a constant trend and 10 others showed irregular CL fluctuations. The monomorphic character of the tachycardias was established by principal-component analysis, which also indicated that CL dynamics associated with the accelerating and decelerating trends may be related to shortening and prolongation of activation times, respectively, occurring in equal proportion at all recording sites. In canine preparations in which reentry circuits could be mapped with high resolution, CL showed an accelerating trend in rate when circus movement of excitation occurred around a transmural scar in muscle generating unipolar electrograms with relatively high -dV/dtmax, and a decelerating trend in rate occurred when functional reentry occurred in muscle generating unipolar electrograms with depressed -dV/dtmax. Beat-to-beat CL variations may occur at the onset of sustained monomorphic ventricular tachycardia as a result of uniform acceleration or deceleration of activation times while the overall activation pattern remains constant. The associated initial trends in the rate of sustained monomorphic ventricular tachycardia follow typical patterns that might provide "signatures" corresponding to reentry substrates with distinctive functional properties.

Effect of the K + channel openers NIP-121 and cromakalim on melittin-induced relaxation of guinea-pig isolated trachea

We have investigated the effect o f the K + channel openers (+)-7,8- dihydro-6,6-dimethyl-7-hydroxy-8-(2-oxo-piperidin-1-yl)-6H-pyrano[2,3f]benz-2, 1,3-oxadiazole (NIP-121) and cromakalim on the relaxation induced by the phospholipase A2 activator melittin in guinea-pig isolated trachea. Melittin (0.1 to 3.0 μg/ml caused concentration-dependent relaxation of tracheal spirals precontracted with LTD 4. The magnitude of relaxation was about 40% of that obtained by 1 mM aminophylline. Melittin-induced relaxation was also observed in tracheas precontracted with histamine or the thromboxane A 2 mimetic U46619. The relaxation to melittin was prevented by the cyclooxygenase inhibitor indomethacin (5 μM) or by removal of the tracheal epithelium, suggesting that cyclooxygenase products, possibly dependent on the epithelium, may be implicated in the response to melittin. Pretreatment of tracheas with NIP-121 (0.03 μM) or cromakalim (0.4 μM) did not affect the contraction to LTD 4 but enhanced the relaxation to melittin. This enhancement to melittin was completely inhibited by the ATP-dependent K + channel blocker glibenclamide (1 μM). Higher concentrations of NIP-121 (0.1 μM) or cromakalim (1 μM) did not enhance the response to melittin. In the presence of indomethacin, NIP-121 (0.03 μM) or cromakalim (0.4 μM) enhanced PGE 2 induced relaxation of tracheas precontracted with LTD 4. These results suggest that cyclooxygenase products, possibly dependent on the epithelium, may be involved in melittin-induced relaxation. The enhancement of relaxation to melittin by IK + channel activation might be due, at least in part, to an increased.

Neuromuskul�re Blockade nach Atracurium und Alcuronium unter dem Einflu� von Propofol und Thiopental

Does propofol or thiopentone enhance the effect of nondepolarizing muscle relaxants? We evaluated the effects of propofol and thiopentone on the pharmacodynamics of atracurium and alcuronium in 43 surgical patients (ASA I and II) under general anaesthesia. The patients were randomized into five groups, A-E. Anaesthesia was induced in all patients with fentanyl 4 micrograms/kg i.v. Patients in groups A and C patients received thiopentone 7 mg/kg i.v., and relaxation was achieved with alcuronium 0.25 mg/kg (group A) and atracurium 0.5 mg/kg (group C). Electromyography (train of four, TOF) was used to determine the time of onset of relaxation (AZ) and the maximum degree of blockade (T%). The recovery times to 25%, 50% and 75% of baseline muscle strength were recorded. Additionally, the TOF ratio T4:T1 was calculated, indicating the probable end of relaxation at a ratio of 0.7. At the beginning of the recovery phase (T1 = 15%) propofol 1% 3 mg/kg was given, and the effect on the TOF was measured. Patients in groups B and D patients received total intravenous anaesthesia (TIVA) with propofol 1% 6-12 mg/kg per hour continuously after induction with 3 mg/kg. The action profile of alcuronium 0.25 mg/kg (group B) and atracurium 0.5 mg/kg (group D) were recorded. Group E patients received thiopentone (10 mg/kg per hour) under the use of atracurium 0.5 mg/kg. Ventilation was performed with 30%/70% oxygen and N2O. The results were analyzed for significance using the Mann-Whitney U-test (P = 0.019). A slight difference in AZ was noted for alcuronium under the use of TIVA between propofol and thiopentone: 13 min and 5 min, respectively. Otherwise, the pharmacodynamics (T% and recovery of neuromuscular function) of the two relaxants exhibited no major differences related to thiopentone, propofol or their combination. The TOF was not influenced under additional propofol application. Noteworthy were the wide distribution of the time course of action (up to 3 h) and the magnitude of T% depression under alcuronium. Propofol and thiopentone have no potentiating influence on the time course of action and the magnitude of relaxation with alcuronium and atracurium. Pharmacodynamics of nondepolarizing muscle relaxants do not seem to be influenced by these two hypnotics.

Attenuation of Platelet-Induced Vasorelaxation by Pretreatment of Platelets with Oxidized Low Density Lipoproteins: Important Role of Serotonin

Aggregating platelets cause relaxation of precontracted vascular tissues with intact endothelium. To determine the modulation of vasorelaxation by lipoprotein-rich platelets, rat platelets were preincubated with buffer, native low density lipoprotein (n-LDL, 100 μg protein/ml), oxidized LDL (ox-LDL, 100 μg protein/ml) or high density lipoprotein (HDL, 100 μg protein/ml) at 37°C for 1 hour, washed twice, and then suspended into organ baths containing precontracted endothelium-intact rat aortic rings. While all platelet preparations caused relaxation of rat aortic rings, the magnitude of relaxation induced by ox-LDL-treated platelets was less than that by buffer-treated platelets (p < 0.05). Pretreatment of platelets with native LDL or HDL did not affect the magnitude of vasorelaxation. Treatment of platelets with the cyclooxygenase inhibitor indomethacin (5 × 10−5 M) did not affect the attenuated vasorelaxation in response to ox-LDL-treated platelets. Pretreatment of aortic rings with the thromboxane (TX) ...

Gender differences in atherosclerosis: possible role of nitric oxide.

The mechanism by which women in the reproductive age group are protected from developing coronary heart disease (CHD) as compared with men of similar age is not known. To elucidate whether there is a gender difference in the rate of atherosclerosis formation, we investigated the rate of development of atherosclerosis in both male and female rabbits fed an identical diet consisting of 2% cholesterol for 10 and 15 weeks. The extent of atherosclerosis was correlated with the amount of basal and stimulated release of nitric oxide (NO) from endothelium-intact aortic rings obtained from these animals. Under identical dietary conditions, the female rabbits fed a high cholesterol diet (HCD) for 10 weeks developed very little atherosclerosis (10% surface involvement) as compared with male rabbits (42% surface involvement). However, no significant gender differences in atherosclerosis were observed after 15 weeks of the HCD. The serum cholesterol, high and low density lipoprotein (HDL and LDL) cholesterol were similar in animals fed the HCD for 10 and 15 weeks. The basal release of NO from endothelium-intact aortic rings was significantly greater in control females as compared with males. The magnitude of endothelium-dependent relaxation of aortic rings obtained from both male and female rabbits fed the HCD were impaired to a similar extent, and this impairment correlated with the duration of hyperlipidemia but not with the extent of atherosclerosis. The arginine content of aortic rings were not different between males (257 +/- 52 nmol/g wet weight) and females (345 +/- 62 nmol/g wet weight) or between control and hyperlipidemic groups (males 312 +/- 69; females 301 +/- 65 nmol/g wet weight). Although the precise mechanism for the slower rate of development of atherosclerosis in the female rabbits as compared with males is not clear, the greater basal release of NO in females before they were fed a hyperlipidemic diet, as well as other factors, may be involved. The impairment of endothelium-dependent relaxation in hyperlipidemic animals is not due to a decrease in the availability of arginine, the substrate for NO.

Decreased endothelium-dependent relaxation in subarachnoid hemorrhage-induced vasospasm: role of ET-1

The purpose of this study was to test whether endothelium-dependent relaxation is decreased during acute vasospasm following subarachnoid hemorrhage (SAH) and the mechanism underlying the decrease. Basilar artery in situ was 35% constricted 3 days following injection of autologous arterial blood into the rabbit cisterna magna compared with vessels from control rabbits. In situ suffusion with the endothelium-dependent relaxant, acetylcholine (ACh; 10 microM), relaxed resting and serotonin (5-HT)-contracted control vessels but not vasospastic and 5-HT-contracted vasospastic vessels. In contrast, the relaxant potency and efficacy of ACh was similar in control and vasospastic vessels contracted with 5-HT in vitro. In situ suffusion with the ETA-receptor antagonist, BQ-123 (1 microM), reversed the vasospasm by 51% and restored the magnitude of ACh relaxation of vasospastic and 5-HT-contracted vasospastic vessels to that of controls. ACh in situ and in vitro relaxed endothelin-1 (ET-1)-contracted control vessels to a smaller magnitude than 5-HT-contracted control vessels. These results suggest, in contrast to previous studies, that endothelium-dependent relaxation is decreased during acute vasospasm following SAH. The decreased endothelium-dependent relaxation is secondary to the underlying ET-1-mediated spasm. The inhibition of endothelium-dependent relaxation observed in situ following SAH cannot be demonstrated in vitro, presumably due to loss of the ET-1-mediated vasospasm.