Phosphatidylinositol-4,5-bisphosphate (PIP2) is a minor phospholipid component of cell membranes but is an important second messenger that regulates diversity of cellular activities, including the activity of ion channels.Cardioactive hormones and other physiologically relevant interventions can modulate cardiac PIP2.One such modulation, carried by Gq coupled receptors, is expected to hydrolyze membrane PIP2.However, some published works suggest that the cardiac PIP2 is not decreased but even increased after stimulated with agonists for Gq coupled receptors such as phenylephrine and endothelin-1, suggesting that the metabolism of membrane phospholipid is a complicated issue.In this study, we found that activation of GPCR with NE (5μM) or Ang Ⅱ (3μM) caused ~20% augment of PIP2 level in primary cultured cardiomyocytes from adult rats, while inhibition of PLC, PKC, PI4K and chelating of Ca2+ could block the effects.Though it increased initially, the total PIP2 level of cardiac myocytes fell back to normal or lower than normal level when treated with NE or Ang Ⅱ for longer time (48h-72h).Furthermore, the PIP2 level in the hearts from the Iso-induced but not from the swimming-induced rat cardiac hypertrophic model was significantly decreased.The results indicate that activation of Gq coupled GPCR dose not reduce but increase the total PIP2 level in cardiomyocytes; this increased PIP2 level may be resulted from an increased synthesis of PIP2 initiated by signaling molecules of the GPCR pathways, including Ca2+.The increased synthesis of membrane PIP2 level in hearts is a positive response to hypertrophic stimulation, which may underlie the compensatory maintenance of cardiac function in the early stage of cardiac hypertrophy.