Mechanisms of atrial natriuretic peptide (ANP) secretion by rat hearts perfused in vitro--Ca2(+)-dependent signal transduction for ANP release by mechanical stretch.
Effects of temperature, contraction frequency, and intraatrial pressure on immunoreactive ANP release were investigated in isolated rat hearts perfused in Langendorff or working mode. A reduction of temperature from 37 C to 27 degrees C caused a decrease of ANP release by 64% indicating its marked temperature-dependency (Q10 = 2.92). An increase of atrial contraction frequency from 300 to 500/min in Langendorff-perfused hearts did not cause a significant change in the ANP release. An elevation of left atrial filling pressure of working hearts from 8 to 18 and 28 cmH2O was associated with pressure-dependent, and reversible increase of the ANP release. This pressure-induced release of ANP was inhibited in a low calcium (50% Ca2+) medium or by nifedipine (10(-7) M). N-(6-aminohexyl)-5-chloro-1-naphthalene-sulfonamide (W-7, 10(-7)M), a potent calmodulin inhibitor, or ryanodine (10(-8)M) had similar inhibitory action against the pressure-induced increase of ANP release. These results indicate that ANP secretion is primarily regulated by mechanical stretch or distension of the atrial wall, while the atrial contraction frequency is less important as a physiological stimulus for the secretion. The stretch-induced ANP secretion may require an influx of calcium through the voltage-dependent Ca2+ channels. It was also suggested that Ca2+ release from the sarcoplasmic reticulum leading to an activation of calcium-calmodulin kinase may be included in the intracellular processes of ANP release by mechanical stretch.
Katoh
S
S
Department of Circulation and Respiration, Research Institute of Environmental Medicine, Nagoya University, Japan.
Toyama
J
J
Aoyama
M
M
Miyamoto
N
N
Seo
H
H
Matsui
N
N
Kodama
I
I
Yamada
K
K
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D001696:Biomechanical Phenomena; D001794:Blood Pressure; D002118:Calcium / Q000502:physiology*; D002147:Calmodulin / Q000037:antagonists & inhibitors; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology; D010477:Perfusion; D051381:Rats; D011916:Rats, Inbred F344; D012433:Ryanodine / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology*; D013449:Sulfonamides / Q000494:pharmacology; D013696:Temperature
D002147:Calmodulin; D013449:Sulfonamides; D012433:Ryanodine; C017967:W 7; D009320:Atrial Natriuretic Factor; D009543:Nifedipine; D002118:Calcium