Hyperosmolarity, usually defined as solutions that have a higher osmolarity compared with the normal extracellular fluid (around 300 mOsm/L), can be found in different physiological and pathophysiological conditions, such as dehydration, the high osmolarity of the interstitial fluid in the medulla of the kidney or hyperglycemic hyperosmolar syndrome in diabetic patients. The osmolarity can be as high as 1200 to 1400 mOsm/L in such states, 3 times higher than that of normal interstitial fluid around most body cells. Although detrimental to some cell function, acute hyperosmolarity has also been found capable of exerting protection to some extent. Previous studies have shown that small amount of hyperosmotic solutions such as hypertonic saline (7.5% NaCl, 2400 mOsm/L), especially when given in dextran, were effective in shock resuscitations of different causes including sepsis, burn and pancreatitis. In our previous study in diabetes, we found that severe hyperglycemia rendered diabetic hearts resistant to ischemia and reperfusion injury, with significant upregulations of hyperosmolarity-related antioxidants, giving rise to our interest in the innate or adaptive responses of cardiovascular system to hyperosmolarity.