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![Investigation into the mechanism of action underlying the relaxation of vascular smooth muscle by the K-channel opener levcromakalim için kapak resmi Investigation into the mechanism of action underlying the relaxation of vascular smooth muscle by the K-channel opener levcromakalim için kapak resmi](/client/assets/d79c3e4af2b6d196/ctx/images/no_image.png)
Investigation into the mechanism of action underlying the relaxation of vascular smooth muscle by the K-channel opener levcromakalim
Başlık:
Investigation into the mechanism of action underlying the relaxation of vascular smooth muscle by the K-channel opener levcromakalim
Yazar:
Greenwood, Iain A., author.
ISBN:
9780355977769
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (275 pages)
Genel Not:
Source: Dissertation Abstracts International, Volume: 76-08C.
Özet:
The possibility that K-channel openers such as levcromakalim may produce smooth muscle relaxation by a mechanism in addition to the activation of plasmalemmal K-channels has been investigated. The ability of the K-channel openers cromakalim, levcromakalim, aprikalim and RP 49356 to relax precontracted aortic strips was inhibited approximately 4-fold when the tissue was bathed in Rb-substituted physiological salt solution (RbPSS) and contracted by the addition of 20 mM RbCI. The relaxant action of minoxidil sulphate was more markedly inhibited by RbPSS, however the relaxant ability of nifedipine was not affected by the modified PSS. The spasmolytic actions of levcromakalim and RP 49356, but not of nifedipine on the spontaneous activity of the rat portal vein were attenuated approximately 7-fold by RbPSS. Relaxations produced by K-channel openers in RbPSS were transient compared to relaxations produced in normal PSS. Incubation of aortic strips in RbPSS did not affect the ability of glibenclamide (0.1-1 muM) to inhibit levcromakalim-induced relaxations. Incubation of aortic strips in RbPSS abolished the ability of levcromakalim (1 and 10 muM) and aprikalim (5 muM) to increase the rate of 86Rb and 42K efflux. However, RbPSS did not affect the ability of 1 muM levcromakalim to inhibit the refilling of noradrenaline (NA)-sensitive calcium stores in the rat aorta. Single smooth muscle cells were dissociated from rat portal veins, bathed in Ca-free extracellular solution and voltage clamped in whole-cell configuration. Levcromakalim (1 muM) induced the development of a non-inactivating current (lkco) and inhibited the delayed rectifier current (lK(v)). When the cell was bathed in RbPSS, lK(v) was reduced by approximately 40% at a test potential of +30 mV. However, in RbPSS levcromakalim still generated lKco and inhibited lK(v). In comparison, when cells were exposed to RbPSS after the cell had been exposed to levcromakalim in normal extracellular solution, lKco elicited by levcromakalim was supressed. The inhibition of lK(v) was not affected. Inclusion of 5 mM RbCI in the intracellular solution inhibited the development of /Kco by levcromakalim. However, the inhibition of lK(v) was not modified by the presence of RbCI in the pipette. Fura-2 epifluorescence was used to investigate the effects of levcromakalim and nifedipine on the increases in [Ca2+]i produced by 10 muM NA and 30 mM K+-PSS. Whilst nifedipine (0.01-10 muM) abolished both the increase in tension and [Ca2+]; produced by 30 mM K+-PSS, levcromakalim (0.01-10 muM) could only supress the contraction produced by this agent. Both agents reduced the increase in [Ca2+]i evoked by 10 muM NA with a parallel, full reduction in tension. Pretreatment with levcromakalim (1 muM) did not affect the increase in [Ca2+]i induced by both 90 mM K+-PSS or 10 mM caffeine, but did inhibit both the peak and plateau increases in [Ca2+]i in response to 10muM NA. In comparison, levcromakalim inhibited the transient increase in tension produced by 10 muM caffeine, but only inhibited the plateau tension induced by 10 mM NA. Single voltage clamped rat portal vein smooth muscle cells were loaded with the fluorescent Ca-sensitive dye indo-1 (100 muM). Depolarizations positive of -30 mV from a holding potential of -60 mV induced a rapid and transient increase in [Ca2+]i, the amplitude of which decayed over the course of a 10 min experiment. Levcromakalim (1 muM) applied to cells held at -10 mV increased the holding current, but did not affect the [Ca2+]i. Levcromakalim (1 muM) reduced the basal [Ca2+]I of cells held at -60 mV and increased the duration of the Ca-transient in comparison to controls, an effect also produced by 0.5 muM thapsigargin- an inhibitor of the sarcolemmal Ca-ATPase. Both thapsigargin (0.5 muM) and ryanodine (10 muM) increased the spontaneous activity of whole rat portal veins, but did not affect the ability of levcromakalim to inhibit the spontaneous activity in these tissues.
Notlar:
School code: 1543
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Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
---|---|---|---|
XX(683812.1) | 683812-1001 | Proquest E-Tez Koleksiyonu | Arıyor... |
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