Effects of natriuretic peptides on ventricular myocyte contraction and role of cyclic GMP signaling.
Natriuretic peptides, including atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) act through different receptors and at different potencies to affect cardiac myocyte function. We tested the hypothesis that these three peptides would differentially reduce cardiomyocyte function through their effects on the cyclic GMP signaling pathway. Rabbit ventricular myocytes were isolated and stimulated by electrical field stimulation. Cell function was measured using a video edge detector. ANP BNP or CNP at 10(-9), 10(-8), 10(-7) M were added to the myocytes. Intracellular cyclic GMP was determined using a radioimmunoassay in the absence or presence of ANP, BNP or CNP. All natriuretic peptides decreased myocyte contractility in a similar concentration dependent manner. Myocyte percentage shortening was significantly decreased with all peptides at 10(-7) M compared with baseline (ANP from 5.4+/-0.4 to 3.9+/-0.2%; BNP from 5.0+/-0.2 to 3.5+/-0.1%; CNP from 5.6+/-0.3 to 4.0+/-0.3%). Maximum rate of shortening and relaxation were also decreased similarly and significantly. Intracellular cyclic GMP was significantly increased in myocytes treated with ANP, BNP or CNP (Baseline 1.0+/-0.2, ANP 2.1+/-0.2, BNP 2.3+/-0.3, CNP 2.0+/-0.2 pmol/10(5) myocytes). Furthermore, inhibition of the cyclic GMP protein kinase with KT5823 caused a reversal in the functional effects of CNP. We concluded that all natriuretic peptides had similar negative effects on ventricular myocyte function and their effects were accompanied by increased cyclic GMP. Blockade the effect of CNP by a cyclic GMP protein kinase inhibitor demonstrated that effects were mediated through the cyclic GMP signaling pathway.
Zhang
Qihang
Q
Heart and Brain Circulation Laboratory, Department of Physiology and Biophysics, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, Piscataway, NJ 08854-5635, USA.
Moalem
Jacob
J
Tse
James
J
Scholz
Peter M
PM
Weiss
Harvey R
HR
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism*; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D020097:Natriuretic Peptide, Brain / Q000494:pharmacology; D020098:Natriuretic Peptide, C-Type / Q000494:pharmacology; D045265:Natriuretic Peptides / Q000494:pharmacology*; D011817:Rabbits; D015398:Signal Transduction / Q000187:drug effects
D045265:Natriuretic Peptides; D020097:Natriuretic Peptide, Brain; D020098:Natriuretic Peptide, C-Type; D009320:Atrial Natriuretic Factor; D017869:Cyclic GMP-Dependent Protein Kinases; D006152:Cyclic GMP