Changes of beta2-adrenergic stimulation induced by hyperosmosis in human atrium

The purpose of the present study was to determine whether extracellular osmotic pressure modulates beta2-adrenergic stimulation of the contraction force and L-type Ca2+ current in human atrial myocytes.

Experiments were performed on human atrial trabeculae and myocytes isolated from the right atrium. The concentration dependent effect of salbutamol (SAL), a beta2-adrenoreceptor agonist, on peak tension (P) and L-type calcium current (ICaL) under isoosmolar (345 mOsm) and hyperosmolar (405 or 525 mOsm was achieved by adding of mannitol) conditions was studied.

Salbutamol (10 nmol/L-10 micromol/L) added to the control solution increased P by 180.6 +/- 45.8% over control with a half-stimulation constant EC50 = 27 +/- 6 nmol/L. Under isoosmolar conditions SAL (0.1/10(3)nmol/L) increased ICaL by 182.3 +/- 19.8% over control with an EC50 2.9 +/- 0.9 nmol/L. In hyperosmolar solutions the same concentrations of SAL increased P and ICaL by 57.2 +/- 12.6% and 217.2 +/- 70.5% over control with EC50 = 640 +/- 260 nmol/L and 12 +/- 5 nmol/L respectively.

These results indicated that hyperosmolarity reduced the effect of beta2-adrenergic stimulation, i.e. the dose-response curve of salbutamol on L-type calcium current was shifted to the higher concentration range and maximal increase in contraction force was diminished in human atrial cells.