Barnett R, Ortiz P A, Blaufox S, Singer S, Nord E P, Ramsammy L
Department of Medicine, State University of New York, Stony Brook 11794.
Am J Physiol. 1990 Jan;258(1 Pt 1):C37-45. doi: 10.1152/ajpcell.1990.258.1.C37.
The mechanism for the vasorelaxant effect of atrial natriuretic factor (ANF) remains to be clarified. Recent evidence suggests that this agent can antagonize the action of angiotensin II (ANG II) by affecting intracellular calcium metabolism. The biochemical basis for this phenomenon was investigated in cultured rat mesangial cells (MCs), a preparation which exhibits the contractile properties of smooth muscle cells and is responsive to ANG II and ANF. Preincubation of MCs with ANF significantly inhibited ANG II-induced release of inositol trisphosphate (IP3) resulting from hydrolysis of phosphatidylinositol 4, 5-bisphosphate. Similarly, ANG II-stimulated increases in cytosolic free Ca2+ [( Ca2+]i), 45Ca efflux, as well as 45Ca influx were diminished by ANF. In addition, these alterations in Ca2+ kinetics were associated with ANF-mediated antagonism of ANG II-induced phospholipid turnover and prostaglandin (PG) E2 release. Sodium nitroprusside (SNP), which augmented guanosine 3',5'-cyclic monophosphate (cGMP) accumulation to a degree comparable to ANF, likewise inhibited ANG II action on the phosphoinositide (PI) pathway, Ca2+ regulation, and PGE2 production. Collectively our results indicate that the effects of ANF on [Ca2+]i in MCs relate to cGMP-induced alterations of PI metabolism. In this fashion cGMP-elevating agents may influence a variety of calcium-dependent biochemical pathways including prostaglandin synthesis.
心房利钠因子（ANF）血管舒张作用的机制仍有待阐明。最近的证据表明，该因子可通过影响细胞内钙代谢来拮抗血管紧张素II（ANG II）的作用。在培养的大鼠系膜细胞（MCs）中研究了这一现象的生化基础，该细胞制剂具有平滑肌细胞的收缩特性，并且对ANG II和ANF有反应。用ANF预孵育MCs可显著抑制ANG II诱导的由磷脂酰肌醇4,5-二磷酸水解产生的肌醇三磷酸（IP3）释放。同样，ANG II刺激的胞质游离Ca2+[（Ca2+]i）增加、45Ca外流以及45Ca内流也被ANF减弱。此外，Ca2+动力学的这些改变与ANF介导的对ANG II诱导的磷脂周转和前列腺素（PG）E2释放的拮抗作用有关。硝普钠（SNP）使鸟苷3',5'-环磷酸（cGMP）积累增加到与ANF相当的程度，同样抑制ANG II对磷脂酰肌醇（PI）途径、Ca2+调节和PGE2产生的作用。我们的结果共同表明，ANF对MCs中[Ca2+]i的影响与cGMP诱导的PI代谢改变有关。以这种方式，提高cGMP的药物可能会影响包括前列腺素合成在内的多种钙依赖性生化途径。
