Stretch-secretion coupling in atrial cardiocytes. Dissociation between atrial natriuretic factor release and mechanical activity.

We investigated possible relations between excitation-contraction coupling and atrial natriuretic factor (ANF) release in rat atrial muscle using the isolated perifused atria preparation. To this purpose, the extracellular ionic environment was manipulated by replacement of Ca2+ with the polyvalent cations Ba2+, Sr2+, and La3+. Intracellular Ca2+ was altered by treatment with caffeine and ryanodine and by chemical (49 mM K+) depolarization. Replacement of Ca2+ with Ba2+ or Sr2+ abolished atrial spontaneous mechanical activity but did not prevent ANF release. Chemical depolarization also abolished spontaneous mechanical activity and significantly reduced ANF release in Ca(2+)-free media and in 0.625 mM extracellular Ca2+ but had no effect in the presence of 1.25 or 2.5 mM Ca2+, suggesting that changes in cytosolic Ca2+ levels do not affect ANF release in media containing Ca2+ in the physiological concentration range. The kinetics of ANF release observed during caffeine (10(-6) to 10(-2) M) treatment was similar to that seen in atrial preparations without treatment. At 10(-2) M, caffeine induced an increase in atrial beating rate and resting tension. Ryanodine (10(-4) M) pretreatment reduced stretch-induced ANF release by an average 34%, in addition to inhibiting tension development and beating. These findings clearly show marked differences between atrial cardiocytes and most other endocrine cells in terms of the effect of specific changes in the ionic environment on the secretory response; they also support the view that basal ANF release from atrial cardiocytes is not dependent on contractile atrial activity or Ca2+. In fact, Ca2+ appears to tonically inhibit the rate of basal ANF release. We conclude that, although indispensable for excitation-contraction coupling, intracellular Ca2+ transients by influx or from intracellular stores are not essential for basal ANF release. However, a ryanodine-sensitive compartment appears to be partly responsible for the increased ANF output after muscle stretch.