C-type natriuretic peptide has a negative inotropic effect on cardiac myocytes.
C-type natriuretic peptide (CNP) has vasodilatory and antimitogenic actions, but its role in the control of cardiac function is unclear. We studied the effect of CNP on cultured, beating neonatal rat cardiac myocytes. CNP caused a significant reduction in the amplitude of contraction and a significant accumulation of intracellular cyclic GMP. The effect of a membrane permeable cyclic GMP on cell contraction was similar to that of CNP. CNP caused no change in Ca2+ transients. Blockade of natriuretic peptide receptors abolished the effects of CNP on contraction and accumulation of intracellular cyclic GMP. Blockade of cyclic GMP-dependent protein kinase abolished the effect of CNP on myocyte contraction. We conclude that CNP has a negative inotropic effect on neonatal rat cardiac myocytes. The effect of CNP is mediated via natriuretic peptide receptor(s) causing elevation of intracellular cyclic GMP which possibly activates protein kinase and causes attenuation of myofilament sensitivity to Ca2+.
Nir
A
A
Department of Cardiology, Hadassah University Hospital, 91120, Jerusalem, Israel. nir@hadassah.org.il
Zhang
D F
DF
Fixler
R
R
Burnett
J C
JC
Eilam
Y
Y
Hasin
Y
Y
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002227:Carbazoles; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism* / Q000494:pharmacology; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000378:metabolism; D007211:Indoles; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000166:cytology; D020098:Natriuretic Peptide, C-Type / Q000494:pharmacology*; D011134:Polysaccharides / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D017461:Receptors, Atrial Natriuretic Factor / Q000037:antagonists & inhibitors / Q000378:metabolism
D000470:Alkaloids; D002227:Carbazoles; C072551:HS 142-1; D007211:Indoles; D011134:Polysaccharides; C073601:KT 5823; D020098:Natriuretic Peptide, C-Type; D015124:8-Bromo Cyclic Adenosine Monophosphate; D017869:Cyclic GMP-Dependent Protein Kinases; D006162:Guanylate Cyclase; D017461:Receptors, Atrial Natriuretic Factor; C073616:atrial natriuretic factor receptor C; D006152:Cyclic GMP; D002118:Calcium