Interactions between endothelin-1 and atrial natriuretic peptide influence cultured chick cardiac myocyte contractility.
We have previously shown that rat atrial natriuretic peptide (ANP) reduces the contractility of cultured, spontaneously beating chick embryo ventricular cells, an effect opposite to that of endothelin-1. Endothelin-1 has been described as a secretagogue for natriuretic peptides in vitro and in vivo. Natriuretic peptides can inhibit endothelin-1 secretion from cultured endothelial cells, suggesting a negative feedback mechanism between endothelial cells and cardiomyocytes. The aim of this study was to determine whether ANP attenuated the endothelin-1-induced increase in myocyte contractility. Using a video-microscopy system we studied the contractility of isolated cultured chick ventricular myocytes in response to endothelin-1, chicken natriuretic peptide (ChNP), and both. We also used Northern blot analysis to study the time course of ChNP expression in response to endothelin-1. Endothelin-1 (10(-8) M) increased chick cardiomyocyte contractility by 20-25% between 5 and 15 min (P < 0.05). Although ChNP (3 x 10(-7) M) did not significantly change the amplitude of contraction in basal conditions, it prevented the endothelin-1-induced increase in contractility (P < 0.05) when perfused prior to endothelin-1, and reversed it when perfused 5 min after endothelin-1 exposure (P < 0.05). Endothelin-1 significantly increased the accumulation of ChNP mRNA in chick ventricular myocytes as early as the 30 min after exposure (P < 0.05), with a maximal effect after 2 h of stimulation (P < 0.01); no effect was observed after 4 h. These data support an interaction between endothelin-1 and natriuretic peptides as autocrine/paracrine factors regulating the contractile function of chick cardiac myocytes, as well as their antagonistic effects on cardiac cell contractility. The early and transient expression of ChNP mRNA in response to endothelin-1 may be involved in this interaction.
Laboratoire de Pharmacologie, Faculté de Médecine Broussais Hôtel-Dieu, Paris, France.
Y
Y
Bézie
L
L
Mesnard
D
D
Longrois
F
F
Samson
C
C
Perret
J J
JJ
Mercadier
S
S
Laurent
D000704:Analysis of Variance; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D015152:Blotting, Northern; D002478:Cells, Cultured / Q000187:drug effects; D002642:Chick Embryo; D019332:Endothelin-1 / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015870:Gene Expression; D006801:Humans; D009200:Myocardial Contraction / Q000187:drug effects*; D012333:RNA, Messenger / Q000302:isolation & purification; D051381:Rats
D019332:Endothelin-1; D012333:RNA, Messenger; D009320:Atrial Natriuretic Factor