Atrial natriuretic factor decreases cell volume of rabbit atrial and ventricular myocytes

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Abstract
The effect of atrial natriuretic factor (ANF) on cell volume was studied using video microscopy of rabbit atrial and ventricular myocytes. Each cell served as its own control, and relative cell volumes were determined. ANF (1 microM) significantly decreased relative cell volume to 0.929 +/- 0.006 (n = 7) in atrial and 0.930 +/- 0.013 (n = 5) in ventricular myocytes (normalized to volume without ANF). Reduction of volume was detectable at greater than or equal to 0.01 microM ANF, and the ED50 was 0.072 +/- 0.007 microM (n = 15). The effect of ANF also was examined under hypotonic (0.55T, 168 mosmol/l) and hypertonic (1.82T, 560 mosmol/l) conditions; osmolarity was adjusted using mannitol with NaCl fixed at 65 mM. In 0.55T, 1 microM ANF decreased cell volume to 0.941 +/- 0.014 (n = 5) in atrial and 0.942 +/- 0.017 (n = 7) in ventricular cells (normalized to 0.55T without ANF). In contrast, 1 microM ANF had no effect on atrial (n = 13) or ventricular (n = 11) cell volume in 1.82T. The hypothesis that ANF decreases cell volume by inhibiting Na(+)-K(+)-2Cl- cotransport was tested by blocking the cotransporter with bumetanide (10 microM). After inhibition of Na(+)-K(+)-2Cl- cotransport, 1 microM ANF failed to reduce cell volume in either atrial (n = 6) or ventricular myocytes (n = 6). Block of ANF-induced cell shrinkage by bumetanide was not due to changes in cell volume, since similar results were obtained using atrial (n = 7) and ventricular (n = 7) cells swollen in hypotonic (0.80T, 244 mosmol/l) solution. Replacement of Na+ with N-methyl-D-glucamine or Cl- with methanesulfonate abolished the ability of both ANF and bumetanide to decrease volume of atrial and ventricular cells in 1T and 0.8T solution. These data suggest that ANF can decrease the volume of atrial and ventricular cells under isotonic and hypotonic conditions by a mechanism that may involve Na(+)-K(+)-2Cl- cotransport. An ANF-induced decrease in cell volume may act as negative feedback and inhibit the stretch-induced release of ANF from atrial and ventricular cells. Furthermore, it may contribute to cell volume maintenance in myocytes in the setting of congestive heart failure or myocardial hypoxia when ANF release is elevated.