Changes of β²-adrenergic stimulation induced by hyperosmosis in human atrium

Abstract

Purpose: The purpose of the present study was to determine whether extracellular osmotic pressure modulates β²-adrenergic stimulation of the contraction force and L-type Ca² + current in human atrial myocytes. Material and methods: Experiments were performed on human atrial trabeculae and myocytes isolated from the right atrium. The concentration dependent effect of salbutamol (SAL), a β²-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. Results: Salbutamol (10 nmol/L - 10 mol/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÷103 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. Conclusions: These results indicated that hyperosmolarity reduced the effect of β²-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.