Potentiation of carbon monoxide-induced relaxation of rat aorta by YC-1 [3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole]

2000 ◽  
Vol 78 (4) ◽  
pp. 343-349 ◽  
Author(s):  
Brian E McLaughlin ◽  
Marc L Chretien ◽  
Christine Choi ◽  
James F Brien ◽  
Kanji Nakatsu ◽  
...  

The hypothesis that endogenous carbon monoxide (CO), produced during the oxidation of heme catalyzed by heme oxygenase (HO), plays a role similar to that of nitric oxide (NO) in the regulation of cardiovascular tone has been criticized because of the low potency of CO compared with NO in relaxing blood vessels and stimulating soluble guanylyl cyclase (sGC). This criticism has been muted by the demonstration that, in the presence of YC-1 [3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole], CO has similar potency to NO in stimulating sGC activity. In this study, we determined that YC-1 potentiated CO-induced relaxation of rat aortic strips (RtAS) by approximately ten-fold. Furthermore, CO-induced relaxation of RtAS was shown to be mediated through stimulation of sGC because vasorelaxation was inhibited by ODQ (1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one), a selective sGC inhibitor, in the absence and presence of YC-1. A gas chromatographic-headspace method was used to measure CO concentration in Krebs' solution following the addition of CO-saturated saline solution to the tissue bath, in order to provide an accurate determination of RtAS exposure to CO. The tissue bath concentration of CO was shown to be approximately one-half of that calculated to be present. We conclude that should an endogenous compound exist with properties similar to that of YC-1, then the potency of CO as a vasorelaxant in the presence of this factor would be increased. As a consequence, CO could play a role in the regulation of cardiovascular tone, comparable to that of NO.Key words: carbon monoxide; YC-1 [3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole]; vasodilation; rat aorta; gas-chromatographic analysis.

1940 ◽  
Vol 30 (4) ◽  
pp. 622-638 ◽  
Author(s):  
S. K. Kon ◽  
S. Y. Thompson

1. The influence of storage in the light and in the dark at ordinary temperature and in a heated room at 70–80° F. on the carotene content of finely ground artificially dried grass stored in paper sacks and jute sacks was studied. There was an initial drop in carotene content from 61·1 to 46·5 mg./100 g., i.e. 23·9%, in the first month, and a total loss of 31·4% during 6 months' storage (August to February). No difference could be detected either between treatments or types of containers.2. There was a marked loss of carotene during 13 months' storage of baled artificially dried grass and of hays, amounting to 30–40% of the original value.3. Two methods of estimating carotene were compared. The method of Ferguson & Bishop (1936) gave higher results than the method of Peterson, Hughes & Freéman (1937). The difference is probably due to incomplete extraction in the latter method.4. Chromatographic analyses of “carotene” fractions from the above grasses showed the presence of coloured impurities amounting to 20·5–33·8% of the total recovered pigments.5. As these impurities are biologically inactive, chromatographic analysis or the use of special solvents are probably necessary for the accurate determination of carotene in forage.


1994 ◽  
Vol 427 ◽  
pp. L55 ◽  
Author(s):  
W. Ubachs ◽  
K. S. E. Eikema ◽  
P. F. Levelt ◽  
W. Hogervorst ◽  
M. Drabbels ◽  
...  

2001 ◽  
Vol 281 (6) ◽  
pp. L1436-L1443 ◽  
Author(s):  
Jay S. Naik ◽  
Benjimen R. Walker

Carbon monoxide (CO) has been proposed to attenuate the vasoconstrictor response to local hypoxia that contributes to pulmonary hypertension. However, the segmental response to CO, as well as its mechanism of action in the pulmonary circulation, has not been fully defined. To investigate the hemodynamic response to exogenous CO, lungs from male Sprague-Dawley rats were perfused with physiological saline solution. Measurements were made of pulmonary arterial, venous, and capillary pressures. Lungs were constricted with the thromboxane mimetic U-46619. To examine the vasodilatory response to CO, 500 μl of CO-equilibrated physiological saline solution or vehicle were injected into the arterial line. Additionally, CO and vehicle responses were examined in the presence of the soluble guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3- a]quinoxalin-1-one (ODQ; 10 μM) or the larger conductance calcium-activated K+(BKCa) channel blockers tetraethylammonium chloride (10 mM) and iberiotoxin (100 nM). CO administration decreased vascular resistance to a similar degree in both vascular segments. This vasodilatory response was completely abolished in lungs pretreated with ODQ. Furthermore, CO administration increased whole lung cGMP content, which was prevented by ODQ. Neither tetraethylammonium chloride nor iberiotoxin affected the CO response. We conclude that exogenous CO administration causes vasodilation in the pulmonary vasculature via a soluble guanylyl cyclase-dependent mechanism that does not likely involve activation of KCa channels.


1930 ◽  
Vol 51 (3) ◽  
pp. 357-367 ◽  
Author(s):  
E. Cowles Andrus ◽  
Edward P. Carter ◽  

1. A method is described for determining the refractory period of the dog's auricle during the normal sinus rhythm. The advantages of the method are: (a) The total stimulating effects of repeated induction shocks are avoided. (b) The action current is recorded from a point one millimeter or less from the point of stimulation. (c) Alterations in the spontaneous rate of the auricle do not interfere with the accurate determination of the refractory period. 2. The values obtained for the normal refractory period and the changes produced by atropine and by stimulation of the vagus agree closely with those of previous observers. 3. The automatic features of the method make possible the determination of the refractory period under adrenalin. This drug brings about a distinct shortening of the refractory period but less than that produced by stimulation of the vagus. 4. During vagal stimulation a single induction shock, introduced soon after the end of the refractory period, frequently produces auricular fibrillation. The cause of this irregularity is discussed and its relation to clinical auricular fibrillation is suggested.


2004 ◽  
Vol 82 (4) ◽  
pp. 218-224 ◽  
Author(s):  
Kinga Jaronczyk ◽  
Loc Bui ◽  
Jonathan M Soong ◽  
Brian E McLaughlin ◽  
Gerald S Marks ◽  
...  

Heme is an essential prosthetic group or substrate for many proteins, including hemoglobin, and hemo enzymes such as nitric oxide synthase, soluble guanylyl cyclase, and heme oxygenase (HO). HO is responsible for the breakdown of heme into equimolar amounts of biliverdin, iron, and carbon monoxide, the latter of which is thought to play a role in the regulation of vascular tone. It is not clear whether the source of heme for cardiovascular functions is derived from uptake from the extracellular milieu or synthesis. In this study, we tested the hypothesis that blood vessels obtain their supply of heme for HO through de novo synthesis. Adult male Sprague–Dawley rat aorta was incubated at 37 °C in Krebs' solution with 1 µM [14C]δ-aminolevulinic acid (ALA). [14C]ALA uptake was linear for about 30 min and reached a plateau at approximately 100 min. The radioactivity was incorporated into porphyrins and heme as determined by esterification of 14C-labelled metabolites and thin-layer chromatography. The first and rate-limiting step of heme biosynthesis is catalyzed by ALA synthase (ALA-S), the activity of which was determined in rat aorta using a radiometric assay, ~250 nmol·(g wet mass)–1·h–1. Inducing HO-1 in rat aorta with S-nitroso-N-acetyl penicil la mine (500 µM) did not increase ALA-S activity as compared with basal activity levels of the enzyme. It appears that there is a sufficient amount of heme available under basal ALA-S activity conditions to meet the increased demand for heme resulting from HO-1 induction. These observations indicate that the complete enzymatic pathway for de novo heme biosynthesis resides in rat aorta and furthermore indicate that de novo heme synthesis is capable of supplying a substantial portion of the heme substrate for HO in the aorta.Key words: heme biosynthesis, vasculature, carbon monoxide, heme oxygenase, δ-aminolevulinic acid synthase.


Author(s):  
R.D. Leapman ◽  
P. Rez ◽  
D.F. Mayers

Microanalysis by EELS has been developing rapidly and though the general form of the spectrum is now understood there is a need to put the technique on a more quantitative basis (1,2). Certain aspects important for microanalysis include: (i) accurate determination of the partial cross sections, σx(α,ΔE) for core excitation when scattering lies inside collection angle a and energy range ΔE above the edge, (ii) behavior of the background intensity due to excitation of less strongly bound electrons, necessary for extrapolation beneath the signal of interest, (iii) departures from the simple hydrogenic K-edge seen in L and M losses, effecting σx and complicating microanalysis. Such problems might be approached empirically but here we describe how computation can elucidate the spectrum shape.The inelastic cross section differential with respect to energy transfer E and momentum transfer q for electrons of energy E0 and velocity v can be written as


Author(s):  
M.A. Gribelyuk ◽  
M. Rühle

A new method is suggested for the accurate determination of the incident beam direction K, crystal thickness t and the coordinates of the basic reciprocal lattice vectors V1 and V2 (Fig. 1) of the ZOLZ plans in pixels of the digitized 2-D CBED pattern. For a given structure model and some estimated values Vest and Kest of some point O in the CBED pattern a set of line scans AkBk is chosen so that all the scans are located within CBED disks.The points on line scans AkBk are conjugate to those on A0B0 since they are shifted by the reciprocal vector gk with respect to each other. As many conjugate scans are considered as CBED disks fall into the energy filtered region of the experimental pattern. Electron intensities of the transmitted beam I0 and diffracted beams Igk for all points on conjugate scans are found as a function of crystal thickness t on the basis of the full dynamical calculation.


Author(s):  
F.A. Ponce ◽  
H. Hikashi

The determination of the atomic positions from HRTEM micrographs is only possible if the optical parameters are known to a certain accuracy, and reliable through-focus series are available to match the experimental images with calculated images of possible atomic models. The main limitation in interpreting images at the atomic level is the knowledge of the optical parameters such as beam alignment, astigmatism correction and defocus value. Under ordinary conditions, the uncertainty in these values is sufficiently large to prevent the accurate determination of the atomic positions. Therefore, in order to achieve the resolution power of the microscope (under 0.2nm) it is necessary to take extraordinary measures. The use of on line computers has been proposed [e.g.: 2-5] and used with certain amount of success.We have built a system that can perform operations in the range of one frame stored and analyzed per second. A schematic diagram of the system is shown in figure 1. A JEOL 4000EX microscope equipped with an external computer interface is directly linked to a SUN-3 computer. All electrical parameters in the microscope can be changed via this interface by the use of a set of commands. The image is received from a video camera. A commercial image processor improves the signal-to-noise ratio by recursively averaging with a time constant, usually set at 0.25 sec. The computer software is based on a multi-window system and is entirely mouse-driven. All operations can be performed by clicking the mouse on the appropiate windows and buttons. This capability leads to extreme friendliness, ease of operation, and high operator speeds. Image analysis can be done in various ways. Here, we have measured the image contrast and used it to optimize certain parameters. The system is designed to have instant access to: (a) x- and y- alignment coils, (b) x- and y- astigmatism correction coils, and (c) objective lens current. The algorithm is shown in figure 2. Figure 3 shows an example taken from a thin CdTe crystal. The image contrast is displayed for changing objective lens current (defocus value). The display is calibrated in angstroms. Images are stored on the disk and are accessible by clicking the data points in the graph. Some of the frame-store images are displayed in Fig. 4.


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