Ouabain-induced increases in resting tone of human hyperplastic prostate following repeated noradrenaline and electrical field stimulation

1 The effect of ouabain on contractions to repeated noradrenaline stimulation and electrical field stimulation of human hyperplastic prostate was examined. Ouabain (1 mu M) did not induce contractile response per se but progressively increased the resting tone (i.e., the tone between one noradrenaline stimulation, or electrical field stimulation, and the following) of human hyperplastic prostate. 2 The increased tone by ouabain following repeated noradrenaline stimulations or electrical field stimulation was fully relaxed by the removal of external calcium, and recovered following restoration of calcium. 3 The effect of noradrenaline on Na+ uptake was measured. Noradrenaline (10 mu M) significantly increased the rate of Na+ accumulation in the presence of ouabain (1 mu M); this stimulatory effect was almost completely blocked by prazosin (0.1 mu M) and ethylisopropylamiloride (100 mu M). In contrast, tetrodotoxin (1 mu M) had no effect on noradrenaline-stimulated Na+ transport in human hyperplastic prostate. 4 Intracellular Na+ loading by noradrenaline (10 mu M) in the presence of ouabain (1 mu M) significantly increased the transmembrane Ca2+ uptake as compared with the absence of ouabain; however, nifedipine (1 mu M) was ineffective on Ca2+ uptake under this condition. 5 Transmembrane Ca2+ efflux was stimulated by noradrenaline (10 mu M) in human hyperplastic prostate; this effect was significantly decreased in the presence of ouabain (1 mu M). 6 It is suggested that the increased tone of human hyperplastic prostate following repeated excitation in the presence of ouabain is due to increased Ca2+ entry and reduced efflux of Ca2+ through the Na+/Ca+ exchange system as a consequence of Na+ pump inhibition by ouabain.