Osmolality- and Na+-dependent effects of hyperosmotic NaCl solution on contractile activity and Ca2+ cycling in rat ventricular myocytes

Hypertonic NaCl solutions have been used for small-volume resuscitation from hypovolemic shock. We sought to identify osmolality- and Na⁺-dependent components of the effects of the hyperosmotic NaCl solution (85 mOsm/kg increment) on contraction and cytosolic Ca²⁺ concentration ([Ca²⁺]_i) in isolated rat ventricular myocytes. The biphasic change in contraction and Ca²⁺ transient amplitude (decrease followed by recovery) was accompanied by qualitatively similar changes in sarcoplasmic reticulum (SR) Ca²⁺ content and fractional release and was mimicked by isosmotic, equimolar increase in extracellular [Na⁺] ([Na⁺]_o). Raising osmolality with sucrose, however, augmented systolic [Ca²⁺]_i monotonically without change in SR parameters and markedly decreased contraction amplitude and diastolic cell length. Functional SR inhibition with thapsigargin abolished hyperosmolality effects on [Ca²⁺]_i. After 15-min perfusion, both hyperosmotic solutions slowed mechanical relaxation during twitches and [Ca²⁺]_i decline during caffeine-evoked transients, raised diastolic and systolic [Ca²⁺]_i, and depressed systolic contractile activity. These effects were greater with sucrose solution, and were not observed after isosmotic [Na⁺]_o increase. We conclude that under the present experimental conditions, transmembrane Na⁺ redistribution apparently plays an important role in determining changes in SR Ca²⁺ mobilization, which markedly affect contractile response to hyperosmotic NaCl solutions and attenuate the osmotically induced depression of contractile activity.