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

Bullfrog hemilungs showed minimal relaxation (9 +/- 2% of the maximal relaxant effect of theophylline, Imax) after a 16 h incubation in 10(-5) M indomethacin, indicating that prostaglandin synthesis plays little or no role in the high intrinsic tone characteristic of this preparation. 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. Ouabain (10(-5) 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. Ouabain-treated hemilungs showed reversal (relaxation) of the normal contractile response to 26 mM potassium and marked impairment of the contractile response to calcium in calcium-depleted preparations. These effects suggest that ouabain-induced relaxation reflects a drug action on calcium movements. The marked relaxation (30 to 40% of Imax) produced by 26 mM 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.