Effects Of Hypertonic And Hyperkalemic Solution Of ANP Secretion In Beating Rabbit Atria

Effects of hypertonic and hyperkalemic solution of ANP secretion in beating rabbit atriaAs an endocrine gland, the heart generating and secreting natriuretic peptides (NPs) and participate in regulating body fluid and blood pressure. Since 1981 De Bold et al discovered atrial natriuretic peptide (ANP) in the atria, there are four members in NPs including ANP, BNP (brain natriuretic peptide, BNP), CNP (C-type natriuretic peptide, CNP) and DNP (dendroaspis natriuretic peptide, DNP). It was known that all of the NPs members incorporate a seventeen-residue intra-molecular disulfide loop of amino acids and involved in vasorelaxation, decreasing blood pressure, diuresis and natriuresis, inhibition of cellular proliferation, regulating immunization, protecting cell and lipolysis by combining with natriuretic peptide receptor which is stored in heart, blood vessel, central nervous system, lymph tissue, reproductive organs and kidney.Previous studies shown that rising atrial blood volume, stretching atrial myocytes, accelerating heart rate or rising blood pressure may increasing atrial ANP secretion and adrenergic, cholinergic and peptidic receptors were involved in regulating atrial secretion of ANP. Furthermore, (ET)-1 which can promote to ANP secretion via the receptor of ET-A is regarded to be the most important factor that regulates atrial ANP secretion.Clinical and experimental data shown that hypertonic solution (NaCl) obviously increased renal blood flow, urine volume and creatinine and promoted to excreting of internal metabolites and improved nephric function while it was demonstrated that ANP led a principal roles in it. In addition, some experiments suggested that hyperosmolality promoted ANP secretion mainly by Ca2⁺ regulation. Chan et al discovered that the most patients with an inhibition of renin-aldosterone system (SAS) showed high levels of internal ANP release by observing 34 patients with hyperkalemia. However, the mechanism by which hypertonicity and hyperkalemia regulate ANP secretion is not clear. Therefore, the purpose of present study is to define the effects of hypertonicity and hyperkalemia on the regulation of atrial ANP secretion in perfused beating rabbit atria. The results of the present study showed that:1,Perfusion with hypertonic solution, constituted by 30, 60, 100 mmol/L mannitol respectively, significantly increased ANP secretion (all P＜0.01) and the atrial stroke volume (all P＜0.01) by dose-dependent manner. The changes in atrial pulse pressure was also significantly increased at 30 mmol/L mannitol (P＜0.01) and reached the peak at 60 mmol/L mannitol (P＜0.01) and showed decreasing tendency at 100 mmol/L mannitol (but higher than the control levels, P＜0.01 vs control). The most effects of hypertonic solution on ANP secretion and atrial dynamics were observed at 60 mmol/L minnitol.2,L-type Ca²⁺ channel blocker nicardipine (1.0μmol/L) blocked the effect of hypertonic solution-induced increase of ANP secretion and stroke volume. However, ryanodine (1.0μmol/L), a blocker of myocytic sarcoplasmic reticulum Ca²⁺ release, failed to modulation of ANP secretion with decreased in atrial stroke volume (P＜0.01).3,ATP-sensitive potassium channel (K_ATP) blocker glibenclamide (1.0μmol/L) failed to modulation of hypertonic solution-induced increase of ANP secretion with significantly inhibited in atrial stroke volume.4,Hyperkalemic solution (120% K⁺ of HEPES buffer) significantly increased ANP secretion (P＜0.01) without changes in atrial stroke volume (P＞0.05).5,ATP-sensitive potassium channel blocker glibenclamide (1.0μmol/L) blocked the effect of hyperkalemia-induced increase of ANP secretion without changes in atrial stroke volume. Voltage-dependent potassium channel blocker TEA (tetraethylammonium chloride) also blocked the effect of hyperkalemia-induced increase of ANP secretion with decreased in atrial stroke volume (P＜0.05).6,L-type Ca²⁺ channel blocker nicardipine (1.0μmol/L) obviously attenuated the effect of hyperkalemic solution-induced increase of ANP secretion with inhibited in atrial stroke volume (P＜0.01).These results indicate that:1,Hypertonic and hyperkalemic solution stimulated ANP secretion in perfused beating rabbit atria.2,Hypertonic solution-induced increment of ANP secretion via Ca²⁺-dependent signaling pathway.3,ATP sensitive- and voltage-gated K⁺ channel were involved in the regulation of hyperkalemic solution-promoted atrial ANP secretion in perfused beating rabbit atria and L-type Ca²⁺ channel was also involved in it.