Role of calcium in stretch-induced release and mRNA synthesis of natriuretic peptides in isolated rat atrium.
To investigate the role of Ca2+ in stretch-induced synthesis and release of atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) isolated superfused rat atria were stretched by raising intra-atrial pressure. The immunoreactive (ir-) ANP and BNP concentrations were analysed by radioimmunoassay and the corresponding mRNA levels were quantified by Northern blot and dot blot analyses. Stretch-induced ir-ANP release and a rise in BNP mRNA levels increased at high (3.0 mM) compared to low (0.5 mM) extracellular Ca2+ concentration ([Ca2+]o). Moreover, the adaptation of stretch-induced ir-ANP release was dependent on [Ca2+]o. Atrial BNP mRNA levels were increased by stretch also in non-paced, electrically silent atria, where voltage-activated Ca2+ channels are not activated. The stretch-induced rise in BNP mRNA was blocked by gadolinium (80 microM), but not by the L-type channel blocker diltiazem (3.0 microM). This study indicates that both the stretch-secretion coupling of ir-ANP release and the pressure-stimulated synthesis of BNP mRNA are Ca2+-dependent processes. Gadolinium inhibits the stretch-stimulated rise in BNP mRNA levels in contracting and non-contracting atria, which is similar to its ability to block stretch-activated ir-ANP release, suggesting the involvement of Ca2+-permeable stretch-activated channels.
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Department of Physiology, Biocenter Oulu, University of Oulu, Kajaanintie 52 A, 90220 Oulu, Finland.
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Vuolteenaho
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Ruskoaho
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Weckström
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D000818:Animals; D009320:Atrial Natriuretic Factor / Q000235:genetics* / Q000378:metabolism; D001696:Biomechanical Phenomena; D015152:Blotting, Northern; D002118:Calcium / Q000502:physiology*; D015220:Calcium Channels / Q000502:physiology; D005682:Gadolinium / Q000494:pharmacology; D006325:Heart Atria / Q000378:metabolism; D007700:Kinetics; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D020097:Natriuretic Peptide, Brain; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis*; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D012433:Ryanodine / Q000494:pharmacology
D015220:Calcium Channels; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D020097:Natriuretic Peptide, Brain; D012433:Ryanodine; D009320:Atrial Natriuretic Factor; D005682:Gadolinium; D002118:Calcium