Decreases in ANP Secretion by Lysophosphatidylcholine Through Protein Kinase C

• Published in: Hypertension (Dallas, Tex. 1979) Tex. 1979), 2003-06, Vol.41 (6), p.1380-1385
• Main Authors: Han, Jeong Hee, Cao, Chunhua, Kim, Sung Zoo, Cho, Kyung Woo, Kim, Suhn Hee
• Format: Article
• Language: English
• Subjects: Animals; Arterial hypertension. Arterial hypotension; Atrial Natriuretic Factor - secretion; Biological and medical sciences; Biological Transport; Blood and lymphatic vessels; Calcium - metabolism; Cardiology. Vascular system; Culture Techniques; Enzyme Inhibitors - pharmacology; Experimental diseases; Extracellular Space - metabolism; Heart Atria - cytology; Heart Atria - drug effects; Heart Atria - enzymology; Heart Atria - secretion; Lysophosphatidylcholines - antagonists & inhibitors; Lysophosphatidylcholines - pharmacology; Male; Medical sciences; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - metabolism; Phosphatidylinositol 3-Kinases - antagonists & inhibitors; Phosphatidylinositol 3-Kinases - physiology; Protein Kinase C - antagonists & inhibitors; Protein Kinase C - physiology; Rats; Rats, Sprague-Dawley
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/01.HYP.0000071317.98004.B3

ABSTRACT—Lysophosphatidylcholine (LPC) is an endogenous phospholipid released from the cell membrane during ischemia, and it has potent, local effects on cardiac tissues. LPC has been implicated in arrhythmogenesis during ischemia by increasing intracellular Ca. However, it is not known whether LPC influences atrial release of atrial natriuretic peptide (ANP). The aim of this study was to investigate the effect of LPC on ANP secretion from isolated, perfused, beating rat atria. LPC (10 and 30 μmol/L) caused decreases in ANP secretion in a dose-dependent manner, with slight increases in intra-atrial pressure and extracellular fluid (ECF) translocation. Therefore, the ANP secretion in terms of ECF translocation was markedly decreased by LPC. The order of the suppressive effect of ANP release was stearoyl-LPC>LPC>myristoyl-LPC=lauroyl-LPC. Staurosporine and wortmannin significantly attenuated suppression of the ANP release and an increase in intra-atrial pressure by LPC. High extracellular Mg also attenuated the LPC-induced suppression of ANP release. However, other protein kinase C inhibitors such as chelerythrine, GF 109203X, and tamoxifen citrate did not affect LPC-induced suppression of ANP release. In single atrial myocytes, LPC caused increases in intracellular Ca in a dose-dependent manner. The order of an increase in intracellular Ca by LPC was stearoyl-LPC>LPC>myristoyl-LPC=lauroyl-LPC. An increase in intracellular Ca by LPC was attenuated by staurosporine. These results suggest that LPC-induced suppression of ANP release through protein kinase C/Ca and phosphoinositol-3-kinase might in part play an important role in the development of hypertension.