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PubMed2006

The true Johari-Goldstein beta-relaxation of monosaccharides.

Broadband isothermal dielectric relaxation measurements of anhydrous fructose, glucose, galactose, sorbose, and ribose were made at ambient pressure in their liquidus and glassy states. We found a new secondary relaxation in fructose and glucose that is slower than those seen before by others. This new secondary relaxation also appears in the dielectric spectra of galactose, sorbose, and ribose, and hence it is a general feature of the relaxation dynamics of the monosaccharides. Dielectric measurements at elevated pressure of fructose and ribose show that the new secondary relaxation shifts to lower frequencies with applied pressures, mimicking the behavior of the alpha-relaxation. In contrast, the faster secondary relaxation remains stationary on applying pressure. These results together with other inferences indicate that the slower secondary relaxation bears relations to the alpha-relaxation, and hence, it is the true Johari-Goldstein secondary relaxation of the monosaccharides.

Molecular Structure↗
PubMed2004

Stress relaxation preconditioning of porcine aortic valves.

In uniaxial tensile testing, load preconditioning is used to generate repeatable load/elongation curves and set a "reference state" for subsequent tensile tests. We have observed however, that for porcine aortic valve (PAV) tissues, preconditioning does not lead to repeatable stress relaxation curves. We thus investigated possible experimental protocols that could be used to generate repeatable load/elongation and stress relaxation curves. To quantify repeatability of stress relaxation, we compared normalized loads at the same time points from repeated stress relaxation curves and computed a repeatability ratio. We found that PAV specimens can generate repeatable stress relaxation curves (repeatability ratio >0.95) if they are subjected to at least five cycles of repeated load preconditioning and stress relaxation. We also found that a single cycle of loading/unloading prior to each stress relaxation phase is sufficient to generate repeatable stress relaxation curves. Stress relaxation preconditioning is therefore required to generate repeatable load/elongation and stress relaxation curves. It is expected that such curves will generate more accurate material constants for the characterization and modeling of PAV mechanics.

Animals↗
PubMed1999

Prostanoid receptors involved in the relaxation of human pulmonary vessels.

1. To characterize the prostanoid receptors on human pulmonary smooth muscle involved in vasodilatations, isolated arteries and veins were contracted with norepinephrine (10 microM) and vessels were subsequently challenged with different prostanoid-receptor agonists in the absence or presence of selective antagonists. 2. Prostaglandin D2 (PGD2) and the selective DP-receptor agonist, BW245C, induced relaxations in the contracted human pulmonary venous preparations. The pD2 values were: 6.88+/-0.11 (n=17) and 7.31+/-0.12 (n=5), respectively. The relaxant responses induced by PGD2 were reduced by the selective DP-receptor antagonist, BWA868C, and the estimated pA2 value was 7.84+/-0.16 (n=4). PGD2 and BW245C did not relax contracted human pulmonary arteries. 3. The selective IP-receptor agonists, iloprost and cicaprost, both induced relaxations in the contracted human vascular preparations. The pD2 values for iloprost were: 7.84+/-0.08 (n=6) and 8.25+/-0.06 (n=4) and for cicaprost: 8.06+/-0.12 (n=5) and 8.11+/-0.09 (n=5) in arteries and veins respectively. 4. Prostaglandin E2 (PGE2) and the EP2/EP3-receptor agonist, misoprostol, partially relaxed the contracted venous preparations and the pD2 values were: 8.10+/-0.15 (n=15) and 6.24+/-0.33 (n=3), respectively. These relaxations suggest the presence of an EP receptor in the human pulmonary veins. The contracted human pulmonary arteries did not relax when challenged with PGE2. 5. In human pulmonary venous preparations, the PGE2-induced relaxations were neither modified by treatment with TP/EP4-receptor antagonist, AH23848B (10 and 30 microM, n=6), nor by the DP/EP1/EP2-receptor antagonist, AH6809 (3 microM, n=6). 6. These data suggest that the relaxation induced by prostanoids involved DP-, IP-receptors and to a lesser extent an EP-receptor on human pulmonary venous smooth muscle. In contrast, only the IP-receptor is involved in the prostanoid induced relaxations on human pulmonary arterial smooth muscle.

Female↗
PubMed2006

Neuronal and smooth muscle receptors involved in the PACAP- and VIP-induced relaxations of the pig urinary bladder neck.

BACKGROUND AND PURPOSE: As pituitary adenylate cyclase-activating polypeptide 38 (PACAP 38)- and vasoactive intestinal peptide (VIP) are widely distributed in the urinary tract, the current study investigated the receptors and mechanisms involved in relaxations induced by these peptides in the pig bladder neck. EXPERIMENTAL APPROACH: Urothelium-denuded strips were suspended in organ baths for isometric force recordings and the relaxations to VIP and PACAP analogues were investigated. KEY RESULTS: VIP, PACAP 38, PACAP 27 and [Ala(11,22,28)]-VIP produced similar relaxations. Inhibition of neuronal voltage-gated Ca(2+) channels reduced relaxations to PACAP 38 and increased those induced by VIP. Blockade of capsaicin-sensitive primary afferents (CSPA), nitric oxide (NO)-synthase or guanylate cyclase reduced the PACAP 38 relaxations but failed to modify the VIP responses. Inhibition of VIP/PACAP receptors and of voltage-gated K(+) channels reduced PACAP 38 and VIP relaxations, which were not modified by the K(+) channel blockers iberiotoxin, charybdotoxin, apamin or glibenclamide. The phosphodiesterase 4 inhibitor rolipram and the adenylate cyclase activator forskolin produced potent relaxations. Blockade of protein kinase A (PKA) reduced PACAP 38- and VIP-induced relaxations. CONCLUSIONS AND IMPLICATIONS: PACAP 38 and VIP relax the pig urinary bladder neck through muscle VPAC(2) receptors linked to the cAMP-PKA pathway and involve activation of voltage-gated K(+) channels. Facilitatory PAC(1) receptors located at CSPA and coupled to NO release, and inhibitory VPAC receptors at motor endings are also involved in the relaxations to PACAP 38 and VIP, respectively. VIP/PACAP receptor antagonists could be useful in the therapy of urinary incontinence produced by intrinsic sphincter deficiency.

Adenylyl Cyclases↗
PubMed1997

Nitric oxide is involved in the inhibitory neurotransmission and endothelium-dependent relaxations of human small penile arteries.

1. Alteration in the flow of blood to the penis is thought to be the most frequent organic cause of erectile dysfunction or impotence. However, information concerning the penile small arteries (helicine arteries) which control blood flow between the arterial systemic circulation and the cavernous sinusoids is scarce. Therefore, the purpose of the present study was to investigate the involvement of nitric oxide, which is considered to be the main neurotransmitter in corpus cavernosum, in both the non-adrenergic non-cholinergic inhibitory neurotransmission and the endothelium-dependent responses in human penile small arteries. 2. Penile small arteries (lumen diameter 200-700 microns), which were branches of the human deep penile arteries obtained either from patients undergoing penile surgery or from organ donors, were mounted in microvascular myographs for isometric tension recording and electrical field stimulation was performed in the presence of guanethidine and atropine to block adrenergic neurotransmission and muscarinic receptors, respectively. 3. In phenylephrine-contracted penile small arteries, electrical field stimulation (0.5-32 Hz) induced frequency-dependent relaxations of both endothelium-intact and -denuded preparations. The inhibitor of nitric oxide synthase, NG-nitro-L-arginine (3 x 10(-5) mol/l), abolished the relaxations at the lowest frequencies, while slow-developing relaxations were still observed at high frequencies (16 and 32 Hz). The inhibitory effect of NG-nitro-L-arginine was reversed in the presence of L-arginine (3 x 10(-3) mol/l). Tetrodotoxin totally abolished the relaxations to electrical field stimulation. In contracted small penile arteries in the presence of NG-nitro-L-arginine, the nitrovasodilator sodium nitroprusside induced potent relaxations. 4. The endothelium-dependnet vasodilator acetylcholine induced relaxations of penile small arteries, which were only partially reduced in the presence of NG-nitro-L-arginine. In contrast, the relaxations to acetylcholine of trabecular corpus cavernosum preparations were almost abolished in the presence of NG-nitro-L-arginine. 5. The present study suggests that relaxations of human intracavernosal small penile arteries induced by non-adrenergic non-cholinergic nerve stimulation partially involve nitric oxide and also another inhibitory transmitter causing relaxations resistant to nitric oxide synthase blockade. In addition, endothelium-dependnet relaxations in human small penile arteries are mediated by both nitric oxide and a factor resistant to NG-nitro-L-arginine.

Acetylcholine↗
PubMed1997

Effect of red wine on endothelium-dependent relaxation in rabbits.

1. Published data on the effects of red wine, ethanol and flavonoids on endothelium-dependent relaxation are equivocal. The present study was undertaken to determine the effects of red wine, ethanol and selected flavonoids present in red wine on endothelium-dependent relaxation. 2. Aortic rings from New Zealand White rabbits were set up in organ baths (20 ml) and contracted with noradrenaline (10(-6) mol/l). An attempt was made to elicit dose-dependent relaxant responses to red wine (15, 30, 40, 80 or 120 microliters), ethanol (5.4, 10.8 and 16.2 microliters) and the flavonoids catechin, epicatechin, quercetin and polymeric phenols (10(-7) to 10(-4) mol/l). In some experiments, endothelium-dependent relaxation to cumulative doses of acetylcholine (10(-9) to 10(-6) mol/l) was determined before and after incubating the rings for 15 min with red wine (120 microliters), ethanol (16.2 microliters), quercetin (10(-5) mol/l), catechin (10(-5) mol/l), epicatechin (10(-5) mol/l) and PPs (10(-5) mol/l) respectively. cGMP was also measured in some rings in the control state and after addition of 120 microliters of red wine, sodium nitroprusside (10(-4) mol/l) and polymeric phenols (10(-5) mol/l). 3. Red wine evoked a dose-dependent relaxation in aortic rings. The highest volumes of wine (120 microliters) relaxed the vessels by 71.35 +/- 7.89% of the maximal contraction (8.95 +/- 0.97 g). Polymeric phenols also relaxed the precontracted rings. These responses were abolished by NG-L-arginine methyl ester (L-NAME) and by removal of endothelium. Addition of red wine, polymeric phenols and sodium nitroprusside increased the cGMP content of the rings. In tissues previously incubated with red wine and polymeric phenols, endothelium-dependent relaxation in response to acetylcholine was attenuated. Ethanol had no such effect. 4. Acute exposure of aortic rings to red wine and polymeric phenols evokes an endothelium-dependent relaxation which is mediated by nitric oxide. However, prior exposure to both red wine and polymeric phenols has a second effect in that it attenuates the endothelium-dependent relaxation evoked by acetylcholine. Since this effect is restored by arginine, it is likely to be due to depletion of substrate for nitric oxide synthase.

Animals↗
PubMed2002

Elimination of *O(2)(-)/H(2)O(2) by alpha-lipoic acid mediates the recovery of basal EDRF/NO availability and the reversal of superoxide dismutase-induced relaxation in diabetic rat aorta.

AIM: The aims of this study were to ascertain the mechanism(s) of relaxant action of exogenous superoxide dismutase (SOD) in aortic rings obtained from 12-week, streptozotocin(STZ)-diabetic and age-matched control rats, and to examine the effects of alpha-lipoic acid (ALA) treatment (for 6 weeks, after 6 weeks of untreated diabetes) on SOD-induced relaxations. MATERIALS AND METHODS: Thoracic aorta rings were suspended to isolated tissue chamber, and the changes in isometric tension were recorded. RESULTS: SOD produced a greater relaxation in untreated-diabetic rings compared with control rings. ALA treatment partially reversed SOD-induced relaxation in diabetic aorta. Pretreatment of rings with N(G)-nitro-L-arginine methyl ester (L-NAME, 100 microm) inhibited SOD-induced relaxation. This effect of L-NAME was markedly observed in control and ALA-treated-diabetic rings compared with untreated-diabetic rings. SOD-induced relaxation was also inhibited by catalase (60 U/ml) in untreated-diabetic rings but not in ALA-treated-diabetic and control rings. Pretreatment with the cyclooxygenase inhibitor, indomethacin, or the catalase inhibitor, aminotriazole, had no effect on SOD-induced relaxation in any ring. CONCLUSION: Findings suggested that: (i) in normal physiological conditions, the relaxant effect of SOD is related to the inhibition of superoxide anion radicals (*O(2)(-))-induced endothelium-derived relaxing factor/nitric oxide (EDRF/NO) destruction in the rat aorta; (ii) in diabetic state, excess *O(2)(-) increasingly inhibits basal EDRF/NO, and the dismutation of excess *O(2)(-) to H(2)O(2) is enhanced by exogenous SOD. H(2)O(2) a vasorelaxant molecule, which probably accounts for the increased responsiveness of diabetic rings to exogenous SOD; and (iii) the reversal effect of in vivo ALA treatment on SOD-induced relaxation in diabetic aorta is probably linked with the elimination of *O(2)(-)/H(2)O(2), which mediates the recovery of basal EDRF/NO availability.

Amitrole↗
PubMed2006

Transient lower esophageal sphincter relaxations do not result from passive opening of the cardia by gastric distention.

BACKGROUND & AIMS: Transient lower esophageal sphincter relaxation is the main mechanism for gastroesophageal reflux. Although there is evidence that transient lower esophageal sphincter relaxations are neurally mediated, another school of thought is that transient lower esophageal sphincter relaxations result from gastric distention, which shortens the sphincter to the point where it opens and the pressure decreases. We assessed the relationship of transient lower esophageal sphincter relaxation to gastroesophageal junction opening in an unsedated human model. METHODS: Seven healthy volunteers (6 men and 1 woman, aged 18-53 years) were studied while they were sitting. Manometry was performed by using a sleeve catheter passed through 1 nostril. A 5.3-mm endoscope was placed through the other nostril to obtain a retroflexed view of the cardia. The biopsy channel was connected to a barostat to distend the stomach with air at 15 mm Hg for 30 minutes. Manometric and endoscopic video-recording times were synchronized but scored independently. RESULTS: The transient lower esophageal sphincter relaxation onset invariably preceded gastroesophageal junction opening (median, 5.0 seconds; range, 0.5-20.7 seconds; P < .001). The transient lower esophageal sphincter relaxation nadir also typically occurred before gastroesophageal junction opening (median, 2.1 seconds; range, -4.2 to +19.5 seconds; P < .001). Once open, the gastroesophageal junction moved proximally for the duration of the transient lower esophageal sphincter relaxation. Termination of transient lower esophageal sphincter relaxations occurred about the time the time of gastroesophageal junction closure. CONCLUSIONS: These data refute the hypothesis that transient lower esophageal sphincter relaxations result from passive mechanical distraction of the gastroesophageal junction. Rather, transient lower esophageal sphincter relaxations must occur before the gastroesophageal junction can open.

Adolescent↗
PubMed2005

Relaxation response of polymers containing highly flexible side groups monitored by broadband dielectric spectroscopy.

The relaxation behavior of poly(5-acryloxymethyl-5-methyl-1,3-dioxacyclohexane), a polymer containing highly flexible side groups, is studied by broadband dielectric spectroscopy in the frequency and temperature ranges 10(-1)-10(9) Hz and 123-473 K, respectively. Above the glass transition temperature T(g) the dielectric loss in the frequency domain exhibits a prominent alpha absorption, followed in increasing order of frequencies by two secondary absorptions called beta and gamma. At temperatures slightly higher than T(g), the a relaxation is well separated from the beta, but as temperature increases overlapping between both relaxations augments forming an alphabeta absorption in the vicinity of 420 K. This latter absorption displays a shoulder on its high-frequency side corresponding to the y relaxation. The strength of the a relaxation decreases with increasing temperature, eventually vanishing at the temperature at which the alphabeta absorption is formed. The time retardation spectra of the isotherms are calculated and further used to facilitate the deconvolution of the overlapping relaxations. The fact that the temperature dependence of the beta relaxation also describes that of the alphabeta absorption suggests that both relaxations have the same nature. It seems that as temperature increases, the a relaxation feeds on the beta absorption until its complete disappearance. The gamma relaxation, in turn, seems to increase at the expense of the alphabeta process at high temperature.

Journal Article↗
PubMed2005

Primary and secondary relaxations in bis-5-hydroxypentylphthalate revisited.

The molecular structure of bis-5-hydroxypentylphthalate (BHPP) is like dihexyl phthalate but having appended to it two hydroxyl end groups, which contribute additional dipole moments and capacity for hydrogen-bond formation. In a previously published dielectric study of the primary and secondary relaxations of BHPP, it was found that all the dynamic properties are normal except for the anomalously large width of the primary relaxation loss peak. There are two secondary relaxations, the relaxation time of the slower one increases with increasing pressure, whereas that of the faster one is practically insensitive to pressure. Hence, the slower secondary relaxation is the "universal" Johari-Goldstein (JG) [J. Chem. Phys. 53, 2372 (1970); 55, 4245 (1971)] relaxation in BHPP. All is well except if the observed large width of the primary relaxation were an indication of a corresponding large coupling parameter n=0.45 in the coupling model. Then the predicted relations between the primary relaxation time tau(alpha) and the JG relaxation time tau(JG) found previously to hold in many glass formers would be violated. It was recognized that this singular behavior of BHPP is likely due to broadening of the primary loss peak by the overlapping contributions of two independent dipole moments present in BHPP, and the actual coupling parameter is smaller. However, at the time of publication of the previous work there were not enough data to support this explanation. By making broadband dielectric measurements of dibutyl phthalate (DBP) and dioctyl phthalate (DOP) that have chemical structures closely related to BHPP but with only one dipole moment, we show that all their dynamic properties are almost the same as BHPP but the widths of their primary relaxation loss peaks are significantly narrower corresponding to a smaller coupling parameter n=0.34. The new data presented here indicate that the coupling parameter of BHPP is about the same as DBP and DOP, and the predicted relations between tau(alpha) and tau(JG) of BHPP are brought back in agreement with the experimental data.

Journal Article↗
PubMed2006

Paramagnetic relaxation of protons in rotationally immobilized proteins.

The proton magnetic relaxation dispersion profiles are reported over the proton Larmor frequency range from 0.01 to 30 MHz for cross-linked gels and for the dry lyophilized bovine serum albumin covalently labeled at lysine with diethylenetriaminepentaacetic acid chelates of either Gd(III) or Mn(II) ions. The proton spin-lattice relaxation dispersion for the cross-linked paramagnetic protein gel is accurately represented as a sum of two major relaxation contributions. The diamagnetic term is a power law from the magnetic field dependence of the protein protons. The paramagnetic term is approximately described by the Solomon-Bloembergen-Morgan class of models. However, the paramagnetic relaxation mechanism in the dry lyophilized protein is fundamentally different and we develop a new quantitative description of the dispersion profile. In the dry case, no peak in the proton relaxation dispersion profile is detected from the field dependence of the electron spin relaxation times. The high-field paramagnetic relaxation dispersion is a power law in the Larmor frequency with an exponent of -0.8, which results from modulation of the electron-nuclear coupling by the intramolecular dynamics of the protein which primarily propagates along the primary structure of the protein. The low-field plateau is caused by the interruption of the electron-nuclear spin correlation by electron spin relaxation. This new quantitative description provides a simple approach to the measurement of electron spin-lattice relaxation times in paramagnetic protein systems at room temperature based on the magnetic field dependence of the proton spin-lattice relaxation rate constant.

Electron Spin Resonance Spectroscopy↗
PubMed1997

Relax promotes ectopic neuronal differentiation in Xenopus embryos.

We previously isolated a novel rat cDNA encoding a basic helix-loop-helix transcription factor named Relax, whose expression in the developing central nervous system is strictly limited to discrete domains containing precursor cells. The timing of Relax expression coincides with neuronal differentiation. To investigate the involvement of Relax in neurogenesis we tested whether Relax activated neural genes in the ectoderm by injecting Relax RNA into Xenopus embryos. We demonstrate that ectopic Relax expression induces a persistent enlargement of the neural plate and converts presumptive epidermal cells into neurons. This indicates that Relax, when overexpressed in Xenopus embryos, has a neuronal fate-determination function. Analyses both of Relax overexpression in the frog and of the distribution of Relax in the rat neural tube strongly suggest that Relax is a neuronal fate-determination gene.

Animals↗
PubMed2000

Role of NO in endothelium-dependent relaxation of rabbit basilar artery in situ.

The purpose of this study was to investigate the possible involvement of endothelium-derived hyperpolarizing factor in endothelium-dependent relaxation of the cerebral vasculature by testing the effectiveness of NO synthase inhibitors at inhibiting endothelium-dependent relaxation in the rabbit basilar artery. Acetylcholine (1.0 microM) and 0.1/0.2 microM sarafotoxin S6c, an endothelinB receptor agonist, relaxed serotonin constricted basilar artery in situ by 100% and 70%, respectively. NG-monomethyl-L-arginine (L-NMMA; 0.1 mM) and 0.3 mM NG-nitro-L-arginine (L-NNA), NO synthase inhibitors, decreased the 1.0 microM acetylcholine- and 0.1/0.2 microM sarafotoxin S6c-induced relaxations by 75% and 45%, respectively. Unexpectedly, the relaxations were abolished by the combination of L-NMMA plus L-NNA. Furthermore, L-arginine (1.0 mM), but not D-arginine, restored the relaxations. Sodium nitroprusside-induced relaxation was also inhibited by L-NMMA plus L-NNA, and the inhibition was reversed by L-arginine. KCl constricted vessels only minimally relaxed in response to sodium nitroprusside, acetylcholine, and sarafotoxin S6c. These results demonstrate that combined NO synthase inhibitors more effectively inhibit endothelium-dependent relaxation than a single inhibitor. The mechanism underlying the greater inhibition due to the combined NO synthase inhibitors may result from both decreased NO release and secondary effects caused by decreased NO release, such as membrane depolarization. The results further suggest that caution should be used with respect to suggestions of the involvement of endothelium-derived hyperpolarizing factor in endothelium-dependent relaxation based upon the partial inhibitory effects of NO synthase inhibitors.

Animals↗
PubMed1984

Phosphorylation of C-protein in intact amphibian cardiac muscle. Correlation between 32P incorporation and twitch relaxation.

The molecular mechanisms by which neurotransmitters modulate the force of contraction of cardiac muscle are incompletely understood. Hartzell and Titus (1982. J. Biol. Chem. 257:2111-2120) have recently reported that C-protein, an integral component of the thick filament, is reversibly phosphorylated in response to ionotropic agents. In this communication, C-protein phosphorylation (as measured by isotopic labeling with 32P) is correlated with changes in the rate of relaxation of twitch tension. On the average, isoproterenol simultaneously increases peak systolic tension twofold, decreases twitch relaxation time from a control value of approximately 450 to approximately 300 ms, and increases C-protein phosphorylation two- to threefold, with a maximum effect occurring less than 60 s after addition of 1 microM isoproterenol. Carbamylcholine, in contrast, decreases peak systolic tension more rapidly than it affects relaxation or C-protein phosphorylation. The maximum decrease in peak tension (60%) occurs within 1 min of addition of 0.5 microM carbamylcholine, but relaxation time increases slowly to 800 ms over approximately 6 min. The increase in relaxation time correlates well with the decrease in 32P incorporation into C-protein (r = 0.94). Changing beat frequency between 0.2 and 1/s has no effect on C-protein phosphorylation but does alter relaxation time (relaxation time decreases approximately 100 ms when beat frequency is changed from 0.5 to 1/s) and thus alters the quantitative relationship between C-protein phosphorylation and relaxation rate. These results suggest that two separate processes affect relaxation. It is proposed that the level of C-protein phosphorylation sets the boundaries over which relaxation is regulated by a second process that is dependent upon beat frequency and probably involves changes in intracellular Ca.

Adenosine↗
PubMed1994

Enhancement of endothelium dependent relaxation in the rat aortic ring by selenium supplement.

OBJECTIVE: The aim was to examine the effect of selenium supplement on endothelium dependent relaxation in rat aortic rings. METHODS: Rats were supplemented with selenium for 3 d (intraperitoneal injection of 4.33 mumol sodium selenite-kg1 body weight.d-1). Saline injections served as controls. Rat aortic ring was precontracted with phenylephrine and endothelium dependent relaxation was produced by the addition of acetylcholine. RESULTS: Acetylcholine-induced endothelium dependent relaxation was enhanced in aortic rings from rats after receiving selenium supplement as compared to control rats. For comparison, endothelium independent vasodilators (sodium nitroprusside and cromakalim) were investigated. Selenium supplement did not affect the relaxation produced by these vasodilators. N-nitro-L-arginine methyl ester (L-NAME) abolished acetylcholine induced relaxation in aortic rings from animals with selenium supplement while indomethacin had no effect on the relaxation. Direct addition of selenium or glutathione peroxidase and glutathione into the organ bath had no effect on acetylcholine induced endothelium dependent relaxation. CONCLUSIONS: The enhanced relaxation after selenium supplement was due to an increase in the release of nitric oxide since L-NAME was effective in blocking the relaxation. The lack of an effect by indomethacin indicated little role for cyclooxygenase products in this system. Our results suggest that the effect of selenium supplement on endothelium dependent relaxation is mediated by cellular changes that cannot be mimicked by the direct addition of selenium or the selenium dependent enzyme glutathione peroxidase.

Acetylcholine↗
PubMed2000

Multiple conformational states of the hammerhead ribozyme, broad time range of relaxation and topology of dynamics.

The dynamics of a hammerhead ribozyme was analyzed by measurements of fluorescence-detected temperature jump relaxation. The ribozyme was substituted at different positions by 2-aminopurine (2-AP) as fluorescence indicator; these substitutions do not inhibit catalysis. The general shape of relaxation curves reported from different positions of the ribozyme is very similar: a fast decrease of fluorescence, mainly due to physical quenching, is followed by a slower increase of fluorescence due to conformational relaxation. In most cases at least three relaxation time constants in the time range from a few microseconds to approximately 200 ms are required for fitting. Although the relaxation at different positions of the ribozyme is similar in general, suggesting a global type of ribozyme dynamics, a close examination reveals differences, indicating an individual local response. For example, 2-AP in a tetraloop reports mainly the local loop dynamics known from isolated loops, whereas 2-AP located at the core, e.g. at the cleavage site or its vicinity, also reports relatively large amplitudes of slower components of the ribozyme dynamics. A variant with an A-->G substitution in domain II, resulting in an inactive form, leads to the appearance of a particularly slow relaxation process (tau approximately 200 ms). Addition of Mg(2+) ions induces a reduction of amplitudes and in most cases a general increase of time constants. Differences between the hammerhead variants are clearly demonstrated by subtraction of relaxation curves recorded under corresponding conditions. The changes induced in the relaxation response by Mg(2+) are very similar to those induced by Ca(2+). The relaxation data do not provide any evidence for formation of Mg(2+)-inner sphere complexes in hammerhead ribozymes, because a Mg(2+)-specific relaxation effect was not visible. However, a Mg(2+)-specific effect was found for a dodeca-riboadenylate substituted with 2-AP, showing that the fluorescence of 2-AP is able to indicate inner sphere complexation. Amplitudes and time constants show that the equilibrium constant of inner sphere complexation is 1.2, corresponding to 55% inner sphere state of the Mg(2+) complexes; the rate constant 6.6 x 10(3) s(-1) for inner sphere complexation is relatively low and shows the existence of some barrier(s) on the way to inner sphere complexes.

2-Aminopurine↗
PubMed1996

Endothelium-dependent relaxation of rat thoracic aorta by amrinone-induced nitric oxide release.

To determine whether amrinone and its induced increase of cyclic AMP releases nitric oxide and enhances endothelium-dependent vascular relaxation, we studied nitric oxide production and vascular relaxation of rat thoracic aorta on treatment with amrinone and forskolin, an activator of adenylate cyclase. When 20 microM amrinone was applied to ring segments of aorta previously contracted with phenylephrine, relaxation was greater in segments with endothelium than in those without (% relaxation 94 +/- 4 vs 37 +/- 7%, P < 0.01). However, a higher concentration of amrinone (> 50 microM) induced the same degree of relaxation in ring segments with or without endothelium, probably due to its direct effect on vascular smooth muscle. The maximal relaxant concentration (100 microM) of amrinone induced an increase (2.5 fold) in cyclic GMP in ring segments. Forskolin also induced concentration-dependent relaxation, but removal of the endothelium attenuated the relaxation induced by forskolin about seven-fold. NG-nitro L-arginine reversed the relaxation induced by amrinone or forskolin in ring segments with, but not without, endothelium. Nitric oxide production in ring segments of aorta, following application of amrinone or forskolin, was detected by nitric oxide-selective electrode and electron paramagnetic resonance spin trapping methods. Pre-treatment with NG-nitro L-arginine or removal of the endothelium suppressed nitric oxide production by amrinone or forskolin. These data showed that amrinone enhances the release of nitric oxide from rat aortic endothelial cells, and induces endothelium-derived relaxing factor/nitric oxide-mediated vasodilation.

Amrinone↗
PubMed1994

Does halothane interfere with the release, action, or stability of endothelium-derived relaxing factor/nitric oxide?

BACKGROUND: Halothane attenuates endothelium-dependent relaxation. To differentiate halothane's effect on endothelium-derived relaxing factor/nitric oxide (EDRF/NO) production from its effect on nitric oxide action on vascular smooth muscle, halothane's effect on endothelium-dependent relaxation was studied in a bioassay system. METHODS: Indomethacin-treated, bovine aortic endothelial cells (BAEC) grown on microcarrier beads, continuously perfused by oxygenated and carbonated (95% O2, 5% CO2) Krebs-Ringer solution served as nitric oxide donors while an isolated denuded rabbit aortic ring directly superfused by the effluent of the BAEC and precontracted with phenylephrine was used to detect EDRF/NO release. The effect of basal and bradykinin-stimulated EDRF release on the tension of the vascular ring was measured. In the bioassay, it was possible to treat either the vascular denuded ring alone or the vascular ring plus the BAEC with halothane by adding it to the perfusate either upstream or downstream from the BAEC. Halothane (final concentration 2.2%) was added to the perfusate at these two positions, and its effect on the relaxation induced by EDRF/NO was determined. In some experiments, the preparations were treated with hemoglobin or L-monomethyl-L-arginine to attenuate the relaxation induced by the EDRF/NO pathway. Finally, halothane's effect on vascular relaxation induced by an increasing concentration of sodium nitroprusside was measured. Halothane's concentration in the perfusate was determined by gas chromatography using electron capture for anesthetic measurement. RESULTS: EDRF/NO released by the BAEC was responsible for the relaxation of the vascular ring. Halothane added to the perfusate potentiated the tension induced by phenylephrine (7.1 +/- 1.89%) and attenuated the relaxation induced by the release of EDRF/NO. This effect was reversible after discontinuation of halothane. Halothane's effect was present even when the anesthetic was added to the perfusate downstream to the perfusion of the endothelial cells. Halothane had no effect on the vascular relaxation induced by sodium nitroprusside. CONCLUSIONS: The authors' data demonstrate that halothane does not interfere with endothelial cell release of EDRF/NO and its smooth muscle cell relaxation but seems to modify either EDRF/NO half-life or its activated redox form.

Animals↗