Abstract： The aim of the present study was to investigate the influence of osmotic pressure on myocardial contractility and thepossible mechanism. Electrical stimulation was used to excite papillary muscles of the left ventricle of Sprague-Dawley (SD) rats. Thecontractilities of myocardium in hyposmotic, isosmotic, and hyperosmotic perfusates were recorded~ The influences of agonist andantagonist of the transient receptor potential vanilloid 4 (TRPV4) on the contractility of myocardium under hyposmotic, isosmotic andhyperosmotic conditions were observed. The results were as follows: (1) Compared with that under isosmotic condition (310 mOsm/L),the myocardial contractility was increased by 11.5%, 21.5% and 25.0% (P<0.05) under hyposmotic conditions when the osmoticpressure was at 290, 270 and 230 mOsm/L, respectively; and was decreased by 16.0%, 23.7% and 55.2% (P<0.05) under hyperosmoticconditions when the osmotic pressure was at 350, 370 and 390 mOsm/L, respectively. (2) When ruthenium red (RR), an antagonist ofTRPV4, was added to the hyposmotic perfusate (270 mOsm/L), the positive inotropic effect of hyposmia was restrained by 36%(P<0.01); and when RR was added to the hyperosmotie perfusate (390 mOsm/L), the inhibitory effect of hyperosmia on myocardialcontractility was increased by 56.1% (P<0.01). (3) When 4-α-phorbol-12,13-didecanoate (4αt-PDD), an agonist of TRPV4, was addedto the isosmotic perfusate (310 mOsm/L), the myocardial contractility did not change; and when 4α-PDD was added to the hyperosmoticperfusate (390 mOsm/L), the inhibition of myocardial contractility by hyperosmia was increased by 27.1% (P<0.01). These resultsobtained indicate that TRPV4 is possibly involved in the osmotic pressure-induced inotropic effect.