Attenuation of negatively regulated ANP secretion by calcium in hypertrophied atria.
Abnormal intracellular Ca(2+)-handling has been described in various heart diseases associated with cardiac hypertrophy. The crucial role of Ca(2+) in the excitation-secretion coupling in atrial cardiomyocytes is not well established. To investigate modulation of atrial natriuretic peptide (ANP) secretion regulated by Ca(2+) in hypertrophied atria, responsiveness of stretch-induced ANP to Ca(2+) was studied using isolated perfused quiescent hypertrophied rat atria. Male Sprague-Dawley rats were given a single subcutaneous injection of 50 mg/kg monocrotaline (MCT) and were sacrificed at 5-6 weeks. In isolated perfused hypertrophied right atria from MCT rats, changes in atrial volume induced by increased atrial pressure caused proportional increases in mechanically stimulated extracellular fluid (ECF) translocation and stretch-induced ANP secretion. Stretch-induced ANP secretion was markedly increased by the depletion of extracellular Ca(2+). However, an accentuation of stretch-induced ANP secretion by Ca(2+) depletion was markedly attenuated in hypertrophied right atria, as compared to control right atria. Therefore, stretch-induced ANP secretion in terms of ECF translocation by Ca(2+) depletion in hypertrophied atria was significantly lower than in control right atria. However, no significant differences were observed between nonhypertrophied and control left atria. Depletion of extracellular Ca(2+) caused a decrease in intracellular calcium in single beating atrial myocytes, which was significantly attenuated in hypertrophied atrial myocytes. The results suggest that attenuation of Ca(2+)-induced negative regulation of ANP secretion in hypertrophied atria may be due to the disturbance of intracellular Ca(2+) regulation.
Kim
Suhn Hee
SH
Department of Physiology, Medical School, Institute for Medical Sciences, Jeonbug National University, 2-20 Keum-Am-Dong-San, Jeonju 560-180, South Korea. shkim@moak.chonbuk.ac.kr
Cao
Chunhua
C
Han
Jeong Hee
JH
Kim
Sung Zoo
SZ
Cho
Kyung Woo
KW
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D002118:Calcium / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D020013:Calcium Signaling / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D025461:Feedback, Physiological / Q000187:drug effects; D006325:Heart Atria / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D017380:Hypertrophy, Right Ventricular / Q000378:metabolism / Q000473:pathology*; D066298:In Vitro Techniques; D008297:Male; D016686:Monocrotaline / Q000494:pharmacology; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley
D016686:Monocrotaline; D009320:Atrial Natriuretic Factor; D002118:Calcium