Effects Of Ca²⁺ Released From Sarcoplasmic Reticulum On Atrial Natriuretic Peptide Secretion In Rabbit Atria

As an endocrine gland,the heart generates and secrets natriuretic peptides. The family of natriuretic peptides hormone is stored in human and mammals,the members in NPs including ANP(atrial natriuretic peptide,ANP),BNP(brain natriuretic peptide,BNP),CNP(C-type natriuretic peptide,CNP) and DNP (dendroaspis natriuretic peptide,DNP).It is known that all of the NPs members have important biological effects,such as diuresis and natriuresis,regulating body fluid and blood pressure.ANP is secreted by atrial myocytes.It is participates in vasorelaxation, decreasing blood pressure,diuresis and natriuresis,inhibition of cellular proliferation,regulating immunization,protecting cell and lipolysis by combining with natriuretic peptide receptors,which are stored in cardiovascular system, central nervous system,lymph tissue,reproductive organs and kidney.ANP is the first member of NPs.By investigation,atrial stretch(eg.elevate venous blood volume) plays an important role in regulation of atrial ANP secretion.Atrial swelling or rising intra-auricular pressure is a factor which stimulates atrial secretory granule secret ANP.In addition,humoral factor can contribute atrial ANP secretion.Glucocorticoid stimulates ANP secretion in vivo,angiotensinâ…¡, phentolamine,endothelin,antidiuretic hormone and prostaglandin also increase plasm ANP concentration by intravenous injection.In contrast,nitric oxide inhibits atrial ANP secretion.High extracellular osmolarity,high K⁺ and high Na⁺ concentration or hypoxia promotes ANP secretion in isolated heart.But the roles of adrenergic,cholinergic and peptidergic receptors on regulation of ANP release are controversial.At present,several studies indicate that Ca²⁺ and cAMP had been related with atrial ANP secretion,cAMP produced by cAMP elevating agents inhibits atrial ANP secretion.But the role of Ca²⁺ in regulation of ANP release is controversial.As the second messenger,Ca²⁺ promotes the process of excitation-contraction coupling(ECC).In the cardiac muscle,the action potential opens voltage-sensitive Ca²⁺ channels in the T tubule membrane;Ca²⁺ diffuses from the extracellular fluid through these channels into the cells,causing a small increase in cytosolic Ca²⁺ concentrateion in the region of the T tubules and adjacent sarcoplasmic reticulum(SR).This small increase in Ca²⁺ concentrateion then causes the opening Ca²⁺-sensitive channels in the SR,resulting in the release of a large amount of Ca²⁺ from this organelle.It is mainly this Ca²⁺ that causes the cardiac contraction.Thus,even though most of the Ca²⁺ causing contraction comes from the SR is dependent on the movement of extracellular Ca²⁺ into the cell,the Ca²⁺ then acting as the signal for releasee of the SR Ca²⁺(this process is called calcium-induced calcium release,CICR).Several studies showe that increase in Ca²⁺ influx via activation of cellular membrane L-type Ca²⁺ channels inhibits atrial ANP secretion in the beating atrium and the perfused heart model. In contrast,other reportes indicat that activation of cellular L-type Ca²⁺ channels increase atrial ANP secretion in the perfused atrium and cultured atrial myocytes. In addition,Jin et al.to claim that hypertonic solution can increase of atrial ANP secretion,this effect may relate to cellular membrane L-type Ca²⁺ channels activity and activation of SR.However,the effects of Ca²⁺ released from SR and intracellular Ca²⁺ concentration on ANP secretion is still unknown.Thus the present study was designed to define the effect of Ca²⁺ released from SR and intracellylar Ca²⁺ concentration on the atrial ANP secretion in perfused beating rabbit atria.The results of this study show:1.Ryanodine(3.0μmol/L),Ca²⁺ transport blocker of sarcoplasmic reticulum,increased atrial ANP secretion(P＜0.01) concomitantly with decreased atrial stroke volume(P＜0.001) and pulse pressure(P＜0.001).2.Caffeine(1.0 mmol/L),an activator of sarcoplasmic reticulum,inhibited ANP secretion(P＜0.001) with increased in atrial stroke volume(P＜0.001) and pulse pressure(P＜0.001).3.Forskolin(1.0μmol/L),a direct activator of adenylyl cyclase strongly inhibited ANP secretion(P＜0.01) concomitantly with increased in atrial stroke volume(P＜0.01) and cAMP efflux(P＜0.01). 4.Nifedipine(1.0μmol/L) or Diltiazem(10.0μmol/L) as L-type Ca²⁺-channel blocker significantly increased ANP secretion(P＜0.05),but failed to modulation the effect of caffeine-induced inhibition of ANP secretion.5.2,3-butanedione monoxime(10.0mmol/L),a cardiac excitation-contraction coupling desensitizer,increased ANP secretion(P＜0.001) with decreased in atrial stroke volume(P＜0.001) as well as pulse pressure (P＜0.001).These results indicate that:1.Activation of sarcoplasmic reticulum or L-type Ca²⁺-channels may increase intracellular Ca²⁺ concentration and inhibit atrial ANP secretion,otherwise to promote atrial ANP secretion.2.Extracellular Ca²⁺ influx was inhibited failed to modulation of caffeine-induced inhibition ANP secretion.3.Atrial dynamics decrease promote atrial ANP secretion may be via the attenuation of Ca²⁺ and troponin binding affinity.