To clarify the role of the endolymphatic sac (ES) in the regulation of endolymphatic pressure, the effects of isoproterenol, a -adrenergic receptor agonist, and acetazolamide, a potent carbonic anhydrase inhibitor, both of which decrease ES direct current potential on cochlear hydrostatic pressure, were examined in guinea pigs. When isoproterenol was applied intravenously, hydrostatic pressures of cochlear endolymph and perilymph were significantly increased with no change in endocochlear potential or the hydrostatic pressure of cerebrospinal fluid. Acetazolamide produced no marked change in the hydrostatic pressure of cochlear endolymph. In ears with an obstructed ES, the action of isoproterenol on the hydrostatic pressure of cochlear endolymph and perilymph was suppressed. These results suggest that the ES may regulate the hydrostatic pressure of the endolymphatic system via the action of the agents such as catecholamines on the ES. direct current potential; isoproterenol; acetazolamide THE ENDOLYMPHATIC SAC (ES), which is a part of the inner ear, is believed to absorb endolymph, since surgical blockage of the ES and the endolymphatic duct causes accumulation of endolymph in the cochlea and vestibule, as so-called endolymphatic hydrops (11), a characteristic pathological finding in Meniere's disease. Endolymphatic hydrops in the cochlea causes deafness, while endolymphatic hydrops in the vestibule causes vertigo (22, 31). Endolymph regulation is thus important for hearing and the sense of equilibrium (7,29). Although the ES is generally accepted to contain active ion transport systems and may absorb endolymph (11), no mechanisms of endolymph regulation by the ES have actually been established.ES direct current potential (ESP) and endocochlear direct current potential (EP) are known to be present in the ES and the cochlea, respectively (3, 12, 15). ESP and EP are generated by active ion transports in the ES and cochlea, respectively (3, 15, 21). ESP and EP can thus be used as indices of function for the ES and cochlea, respectively (15, 21). Catecholamines reportedly depress ESP through -adrenergic receptors (19). The finding that isoproterenol, a -adrenergic receptor agonist, at a dose of 12.5 g/kg decreases ESP without changing EP (16), suggests that isoproterenol would suppress active ion transport in the ES without inhibiting active ion transport in the cochlea. Acetazolamide, a potent carbonic anhydrase inhibitor, reportedly depresses ESP more sensitively than EP (32, 33). The result that cotreatment with isoproterenol and acetazolamide at doses producing near-maximum reduction of ESP depresses almost all parts of the ESP, suggesting that isoproterenol and acetazolamide may depress ESP via different mechanisms and that ESP may be composed of isoproterenol-and acetazolamide-sensitive parts (17).The ES has been hypothesized to regulate endolymphatic hydrostatic pressure (4, 9). However, no reports have described hydrostatic pressure regulation by the ES, as direct measurement of endolymphatic hydrostatic ...