Changes of 2-adrenergic stimulation induced by hyperosmosis in human atrium

Zablockaite D, Gendviliene V, Macianskiene R, Skeberdis VA, Jurevicius J, Kanaporis G, Benetis R

Abstract

Purpose: The purpose of the present study was to determine whether extracellular osmotic pressure modulates  2-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 2-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 2-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. 

Key words: 	human atrium, salbutamol, contraction force, L-type calcium current, hyperosmosis.