Effect of hyperosmolarity on beta2-adrenergic stimulation 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. We have studied the effect of salbutamol (SAL), a beta2-adrenoceptor agonist, on peak tension (P), time to half peak tension (tc), time to half relaxation (tr), resting tension (contracture) (C) and L-type calcium current (ICaL) under isosmotic (345 mOsm) and hyperosmotic (525 mOsm in experiments for P, and 405 mOsm for ICaL) conditions. Salbutamol (10(-8)/10(-5) M) added to the control solution increased P, with a half-stimulation constant EC50=(2.7+/-0.6)x10(-8) M (p<0.05) and the maximal stimulation of contraction force Pmax=180.6+/-45.8% (n=10). The time to half peak and time to half relaxation were reduced by salbutamol to 89.1+/-2.7% and 78.8+/-4.1% (n=8), respectively. Mannitol (180 mM) added to the Tyrode solution decreased Pmax to 34+/-5.5%; tc, tr and C were increased to 126.3+/-7.2%, 158.3+/-22.6% (n=4) and 0.54+/-0.22 (n=5) of the control level, respectively. Under these hyperosmotic conditions the same concentrations of SAL increased P with a half-stimulation constant EC50=(6.4+/-2.6)x10(-7) M and Pmax=57.2+/-12.6% (n=4). The tc and tr were reduced by 23.2+/-5.9% and 53.1+/-19.4% (n=4), respectively (as compared to mannitol). There was no significant effect of salbutamol on the resting tension induced by mannitol. Under isosmotic conditions salbutamol (10(-9)/10(-6) M) increased ICaL with an EC50 value of (2.9+/-0.9)x10(-9) M and Emax 182.3+/-19.8% (n=4). In hyperosmotic solutions the EC50 and Emax for ICaL were (1.2+/-0.5)x10(-8) M and 217.2+/-70.5%, respectively (n=5). These results indicated that hyperosmolarity reduced the effect of beta2-adrenergic stimulation on human atrial cells.