Endothelin: A Potent Stimulus of Atrial Natriuretic Peptide Secretion by Superfused Rat Atria and Its Dependency on Calcium*

Abstract

Endothelin, a hormone secreted by endothelial cells, has potent vasoconstrictive properties. Due to its potential paracrine nature, we examined the effect of endothelin-I on atrial natriuretic peptide (ANP) secretion in vitro. Isolated superfused rat left atria, paced at 2 Hz, were used for study. Endothelin (1-100 nM) increased ANP secretion in a dose-dependent manner from 1.6- to 6.7-fold above baseline. Spontaneously beating right atria increased ANP secretion by 2.3-fold in response to 10 nM endothelin without a change in beat frequency. However, the right atrial ANP secretory response was less than the 3.8-fold increase seen by left atria, and the time to peak response was slower. The calcium dependency of endothelin-stimulated ANP secretion was examined using paced left atria. The dependency of endothelin-stimulated secretion on calcium influx was examined by lowering the superfusate calcium from 1.8 to 0.2 mM. The ANP secretory response to 10 nM endothelin was reduced by 65% with 0.2 mM calcium. Influx of calcium through voltage-dependent calcium channels was examined by superfusion with 50 microM nitrendipine. Nitrendipine decreased endothelin-stimulated ANP secretion by 51% without affecting endothelin binding. The role of intracellular calcium release from the sarcoplasmic reticulum (SR) was examined by superfusion with 1 microM ryanodine, an inhibitor of SR calcium release. Ryanodine had no effect on endothelin-stimulated ANP secretion. We conclude: 1) Endothelin is a potent stimulus of ANP secretion in vitro. 2) The relative secretory response of right atria to endothelin expressed as a function of basal secretion is less and the time to peak secretion delayed relative to left atria. 3) Enhanced calcium influx, primarily through voltage-dependent calcium channels, plays a significant role in endothelin-stimulated secretion. 4) Release of intracellular calcium from the SR does not participate in the secretory response. 5) Part of the stimulatory signal appears to be independent of calcium influx or intracellular calcium release. Thus, endothelin may be an important secretagogue or modulator of ANP secretion in vivo; however, its physiological role in regulating ANP secretion in vivo remains to be determined.

Endothelin antiserum decreases volume-stimulated and basal plasma concentration of atrial natriuretic peptide.

“…19 Both basal and stretch-induced ANP release was stimulated by ET-1 in perfused rat heart preparation.20…”

Role of the Natriuretic Peptide System in Cardiorenal Protection

“…28 In addition, ANP expression may be stimulated directly by Ang II, endothelin-1, or adrenomedullin. 5,29,30 Atrial natriuretic peptide reduces intravascular volume and pressure by means of arterial and venous dilation and enhancement of renal excretion of sodium, chloride, and water. 31,32 It also attenuates production of renin, Ang II, and Ang II-stimulated aldosterone release 33 and inhibits sympathetic nervous system activity.…”

Synergistic activation of salmon cardiac function by endothelin and β-adrenergic stimulation

“…It may act as a tonic regulator of intracellular Ca 2ϩ , which, if interrupted by an endothelin antagonist, may render the ANP-secreting myocytes less sensitive to stretch (20). It has been reported that enhanced Ca 2ϩ influx plays a significant role in ET-1-stimulated ANP secretion but that the release of intracellular Ca 2ϩ from the sarcoplasmic reticulum does not participate in the secretory response (56). In the present study, an ET A antagonist markedly attenuated the load-induced secretion of sCP.…”

“…ET-1 stimulates the secretion of atrial natriuretic peptide (ANP) (14,18,56) and augments the stimulatory effect on ANP release of volume expansion (14,20) and stretch (57), apparently by an ET A -mediated effect (59). We have shown in the rat that the release of ANP induced by volume expansion can be inhibited by the administration of a combined ET A /ET Breceptor antagonist (41).…”