Block of stretch-activated atrial natriuretic peptide secretion by gadolinium in isolated rat atrium.
1. Isolated superfused rat atrial preparations were used to study the mechanism of stretch-induced atrial natriuretic peptide (ANP) secretion. The stretch of the atrial myocytes was induced by raising the intra-atrial pressure. The secretion rates were analysed by measuring ANP concentrations from the superfusate fractions by radioimmunoassay. 2. The effect of gadolinium, a blocker of stretch-activated ion channels, on stretch-induced and basal ANP secretion was investigated by superfusing the atrial preparation with 5, 20 or 80 microM GdCl3. Gadolinium decreased stretch-induced ANP secretion in a dose-dependent manner, but did not affect basal secretion. 3. Because high concentrations of gadolinium may block voltage-gated calcium channels, we tested whether the selective blockers of L-type (diltiazem) and T-type (NiCl2) calcium channels affect the stretch-stimulated ANP release. Neither diltiazem at 3 microM nor NiCl2 at 50 microM affected stretch-induced ANP release in paced atrial preparation. 4. Gadolinium, but not diltiazem, also inhibited stretch-stimulated ANP secretion in non-paced, quiescent atria. 5. The findings that ANP release is inhibited by Gd3+, but not by diltiazem or NiCl2, and that the stretch-induced secretion in quiescent atria is also inhibited by Gd3+, suggest that stretch-activated ion channels are involved in the regulation of stretch-induced ANP release.
Laine
M
M
Biocenter Oulu, Department of Physiology, University of Oulu, Finland.
Arjamaa
O
O
Vuolteenaho
O
O
Ruskoaho
H
H
Weckström
M
M
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D002304:Cardiac Pacing, Artificial; D004110:Diltiazem / Q000494:pharmacology; D005682:Gadolinium / Q000494:pharmacology*; D006325:Heart Atria; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D009532:Nickel / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
C022838:nickel chloride; D009532:Nickel; D009320:Atrial Natriuretic Factor; D005682:Gadolinium; D004110:Diltiazem