Jin Jing Yu, Wen Jin Fu, Li Dan, Cho Kyung Woo
Department of Physiology, Institute for Medical Sciences, Jeonbug National University Medical School, Republic of Korea.
Am J Physiol Regul Integr Comp Physiol. 2004 Nov;287(5):R1101-9. doi: 10.1152/ajpregu.00063.2004. Epub 2004 Jul 15.
Hyperosmolality has been known to increase ANP release. However, its physiological role in the regulation of atrial myocytic ANP release and the mechanism by which hyperosmolality increases ANP release are to be defined. The purpose of the present study was to define these questions. Experiments were performed in perfused beating rabbit atria. Hyperosmolality increased atrial ANP release, cAMP efflux, and atrial dynamics in a concentration-dependent manner. The osmolality threshold for the increase in ANP release was as low as 10 mosmol/kgH2O (approximately 3%) above the basal levels (1.55 +/- 1.71, 17.19 +/- 3.11, 23.15 +/- 5.49, 54.04 +/- 11.98, and 62.00 +/- 13.48% for 10, 20, 30, 60, and 100 mM mannitol, respectively; all P < 0.01). Blockade of sarcolemmal L-type Ca2+ channel activity, which increased ANP release, attenuated hyperosmolality-induced increases in ANP release (-13.58 +/- 4.68% vs. 62.00 +/- 13.48%, P < 0.001) and cAMP efflux but not atrial dynamics. Blockade of the Ca2+ release from the sarcoplasmic reticulum, which increased ANP release, attenuated hyperosmolality-induced increases in ANP release (13.44 +/- 7.47% vs. 62.00 +/- 13.48%, P < 0.01) and dynamics but not cAMP efflux. Blockades of Na+-K+-2Cl- cotransporter, Na+/H+ exchanger, and Na+/Ca2+ exchanger had no effect on hyperosmolality-induced increase in ANP release. The present study suggests that hyperosmolality regulates atrial myocytic ANP release and that the mechanism by which hyperosmolality activates ANP release is closely related to the cross-talk between the sarcolemmal L-type Ca2+ channel activity and sarcoplasmic reticulum Ca2+ release, possibly inactivation of the L-type Ca2+ channels.
已知高渗状态可增加心钠素（ANP）的释放。然而，其在调节心房肌细胞ANP释放中的生理作用以及高渗状态增加ANP释放的机制尚待明确。本研究的目的就是明确这些问题。实验在灌注跳动的兔心房上进行。高渗状态以浓度依赖的方式增加心房ANP释放、环磷酸腺苷（cAMP）流出及心房动力学。ANP释放增加的渗透压阈值低至比基础水平高10毫渗摩尔/千克水（约3%）（10、20、30、60和100毫摩尔甘露醇分别为1.55±1.71、17.19±3.11、23.15±5.49、54.04±11.98和62.00±13.48%；所有P<0.01）。阻断肌膜L型钙通道活性（其可增加ANP释放）可减弱高渗状态诱导的ANP释放增加（-13.58±4.68%对62.00±13.48%，P<0.001）及cAMP流出，但不影响心房动力学。阻断肌浆网钙释放（其可增加ANP释放）可减弱高渗状态诱导的ANP释放增加（13.44±7.47%对62.00±13.48%，P<0.01）及动力学，但不影响cAMP流出。阻断钠-钾-2氯协同转运体、钠/氢交换体和钠/钙交换体对高渗状态诱导的ANP释放增加无影响。本研究提示，高渗状态调节心房肌细胞ANP释放，且高渗状态激活ANP释放的机制与肌膜L型钙通道活性和肌浆网钙释放之间的相互作用密切相关，可能是L型钙通道失活。
