Relaxation of human isolated bronchial smooth muscle

1 Airway preparations of dierent species possess varying degrees of inherent tone which is the result of dierent metabolites of arachidonic acid in dierent species. In human bronchial smooth muscle in vitro we have investigated the eects of 5-lipoxygenase inhibition (zileuton, 10 mM), cyclo-oxygenase inhibition (indomethacin, 1 mM) and mechanical epithelium removal on inherent tone. The shunting of arachidonic acid by inhibition of one or other of these enzymes, as a possible explanation for the eects observed, has also been investigated. 2 Zileuton caused a signi®cant fall in tone either alone (7107+33 mg) or after cyclo-oxygenase inhibition (7203+48 mg) and this eect was not signi®cantly altered by epithelial removal (7191+43 mg alone; 7333+88 mg after indomethacin). Indomethacin increased tone when applied alone (160+94 mg), but this eect only reached statistical signi®cance after 5-lipoxygenase inhibition, (210+81 mg; P50.05). Epithelial removal did not alter the eect of indomethacin when applied alone (213+97 mg), but signi®cantly reduced the eect of indomethacin after 5-lipoxygenase inhibition (34+23 mg; P50.05). 3 These data suggest that inherent tone in human bronchus is largely the result of contractile 5-lipoxygenase products. However, the involvement of cyclo-oxygenase products cannot entirely be discounted, since in the presence of 5-lipoxygenase inhibition contractile and relaxant eicosanoids originating from the bronchial epithelium appear to in¯uence signi®cantly inherent tone.

Section: Introductionmentioning

confidence: 99%

Inherent tone of human bronchus: role of eicosanoids and the epithelium

Watson

Magnussen

Rabe

1997

“…On the other hand, guinea-pig isolated trachealis develops substantial tone which is abolished by indomethacin, suggesting that tone is prostanoidinduced (Farmer et al, 1974;Orehek et al, 1975;Brink et al, 1981;Kawanishi et al, 1984). Spontaneous mechanical tone has also been observed in human tracheal and bronchial smooth muscles (Brink et al, 1980;Huta's et al, 1981;Davis et al, 1982;Ito et al, 1985). However, the effects of indomethacin on the spontaneous tone of human airways smooth muscle are the subject of some debate.…”

Section: Introductionmentioning

confidence: 99%

“…Some workers have shown that indomethacin does not significantly change the basal tone of either fresh or stored human muscle (Brink et al, 1980;Davis et al, 1982). Others have shown that indomethacin increases the basal tone and potentiates the action of histamine or Ca2" (Huta's et al, 1981;Ito et al, 1985). There are also reports indicating that indomethacin suppresses the basal tone of human bronchial smooth muscle strips (Dunlop & Smith, 1975).…”

Section: Introductionmentioning

confidence: 99%

The spontaneous electrical and mechanical activity of human bronchial smooth muscle: its modulation by drugs

Ito

Suzuki

Aizawa

et al. 1989

1 Tissue taken at operation was used to study the electrical and mechanical properties of human bronchial smooth muscle with intracellular microelectrodes and isometric recording of tension changes. 2 Over 90% of the muscle strips exhibited spontaneous tone and 70% produced spontaneous phasic contractions. The resting membrane potential of the smooth muscle cells ranged between -40 to -50 mV with a mean value of -44.9 + 5.2 mV (n = 92 ± s.d.). Spontaneous oscillations of the membrane potential (slow waves) were observed in 90% of the cells examined. 3 The electrical slow waves, phasic contractions and spontaneous tone were greatly reduced by

“…In the guinea-pig tracheal muscle, synthesis of stimulant prostaglandins appears to be responsible for a large fraction of the high intrinsic tone, and indomethacin causes profound relaxation (Farmer et al, 1972;Orehek et al, 1973;1975;Ono et al, 1977), presumably by inhibition of the cyclo-oxygenase pathway. In contrast, indomethacin does not relax human bronchial preparations (Brink et al, 1980;Hutas et al, 1981), suggesting 'that the regulatory role of prostanoids in human airway muscle may be less than in other species' (Brink et al, 1980). Bullfrog lung is of particular interest with respect to intrinsic tone, in that the resting length of the excised lung is near maximal contraction (Downes & Taylor, 1983).…”

Section: Introductionmentioning

confidence: 99%

Mechanisms of intrinsic tone in bullfrog lung: relaxant effects of indomethacin, ouabain and potassium

Downes

Edelstein

Taylor

1986

1 Bullfrog hemilungs showed minimal relaxation (9 ± 2% of the maximal relaxant effect of theophylline, Imax) after a 16 h incubation in 10-0M indomethacin, indicating that prostaglandin synthesis plays little or no role in the high intrinsic tone characteristic of this preparation.2 A higher concentration of indomethacin (10-4 M) produced greater relaxation (23 ± 3% of Imax), but also markedly potentiated isoprenaline-induced relaxation. The interaction with isoprenaline was similar to that previously found for papaverine, a phosphodiesterase inhibitor.3 Ouabain (l0' and 10-4 M) produced an initial contraction followed by marked relaxation (50% of Imax), indicating that a ouabain-sensitive mechanism is of major importance in the maintenance of intrinsic tone. 4 Ouabain-treated hemilungs showed (a) reversal (relaxation) of the normal contractile response to 26mM potassium and (b) marked impairment of the contractile response to calcium in calciumdepleted preparations. These effects suggest that ouabain-induced relaxation reflects a drug action on calcium movements. 5 The marked relaxation (30 to 40% of Imax) produced by 26mM potassium in ouabain-treated hemilungs is of particular interest in that it indicates a mechanism of potassium-induced relaxation distinct from stimulation of sodium-potassium ATPase.