Calcium dependency of frequency-stimulated atrial natriuretic peptide secretion.

Abstract

In this study we examined the mechanism whereby atrial natriuretic peptide secretion is increased when the frequency of contraction is raised from 2 to 5 Hz. We tested the hypothesis that calcium plays a significant role in the frequency-stimulated response. Using superfused rat left atria, we found that lowering the superfusate calcium concentration from 1.8 to 0.2 mmol/L abolished the frequency-stimulated atrial natriuretic peptide secretory response. Superfusion with ryanodine (1 /xmol/L), an inhibitor of sarcoplasmic reticulum calcium release, resulted in a minimal inhibitory effect. Superfusion with 50 junol/L nitrendipine or 10 junol/L diltiazem inhibited the frequency-stimulated response by 46% to 48%. The lack of total inhibition suggested that an additional mechanism of calcium influx was involved, namely, inward calcium movement carried by Na + -Ca 2+ exchange. As intracellular sodium has been reported to rise with an increase in beat frequency, a fall in the sodium gradient would favor inward calcium movement by Na + -Ca 2+ exchange. Because we could not directly assess the role of Na + -Ca 2+ exchange in this experimental paradigm, we examined the effect of lowering the transmembrane sodium gradient on atrial natriuretic peptide secretion by superfusion with the sodium channel activator A trial tachycardias are associated with a rise in / \ plasma atrial natriuretic peptide (ANP) lev-A.JL els. 15 Using an isolated superfused rat atrial preparation, we have found that increasing the frequency of atrial contraction directly increases ANP secretion 6 ; this observation has been confirmed. 7 In the present study, we examined the mechanisms whereby an increase in the frequency of contraction enhances ANP secretion.It has been reported that raising the contraction frequency increases intracellular sodium activity (a' N> ) in rat atrial muscle. 8 In cardiac tissue, a rise in a' N , results in an increase in cytosolic calcium via Na + -Ca 2+exchange. 910 We therefore tested the hypothesis that calcium plays a significant role in the frequency-stimulated ANP secretory response because we and others have noted that calcium appears to play an important role in stimulated ANP secretion. 1115In addition, we attempted to determine the source of the rise in a' Nt , speculating that an increase in Na + -H + antiporter activity may contribute.

Angiotensin-(1–7) stimulates high atrial pacing-induced ANP secretion via Mas/PI3-kinase/Akt axis and Na+/H+ exchanger

“…Frequencyinduced ANP secretion is associated with the activation of NHE, which results in the increase of [Ca 2ϩ ] i by a reversal of the operation mode of the Na ϩ /Ca 2ϩ exchanger (45). However, pretreatment with L-type Ca 2ϩ channel blocker did not affect ANG-(1-7)-augmented ANP secretion in atria with high pacing.…”

Kir6.2-deficient mice are susceptible to stimulated ANP secretion: K channel acts as a negative feedback mechanism?

“…Mechanical stretch in isolated atrial tissues was reported to increase the intracellular Ca 2 + transients and the late duration of the action potentials, which was ascribed to the stretch-induced channel activation and resultant augmentation of the Na + /Ca 2 + -exchanger inward current [21,22]. It has also been proposed that intracellular Ca 2 + plays a critical role in ANP secretion from atrial cells and changes of cytosolic Ca 2 + concentration affect ANP secretion [8,23,24]. Activation of atrial K ATP channels by mechanical stretch may decrease the cytosolic Ca 2 + concentration by abbreviating the action potentials, which is expected to reduce the time for Ca 2 + influx via L-type Ca 2 + channels and to increase the time for Ca 2 + extrusion through the Na + /Ca 2 + -exchange system.…”

Protein kinase-dependent and Ca2+-independent cAMP inhibition of ANP release in beating rabbit atria

“…Increases in Ca 2ϩ influx via L-type Ca 2ϩ -channel activation by BAY K 8644 increased ANP secretion in perfused heart (24,26), isolated beating atria (28,29), and cultured atrial myocytes (18). Similarly, L-type Ca 2ϩ -channel blockers inhibit ANP secretion in perfused heart (26) and isolate beating atria (28,29) and atrial myocytes (5,18). Increased extracellular Ca 2ϩ also results in an increase in ANP secretion in beating atria (15).…”