Nitric oxide and cGMP protein kinase activity in aged ventricular myocytes.
We tested the hypothesis that nitric oxide-induced negative functional effects through cGMP would be reduced in aged cardiac myocytes. Maximum rate of shortening (R(max)) and percent shortening of ventricular myocytes from young (6 mo) and old (3 y) rabbits were studied using a video edge detector. cGMP-dependent phosphorylation was examined by electrophoresis and autoradiography. Myocytes received a nitric oxide donor S-nitroso-N-acetyl-penicillamine (SNAP, 10(-7), 10(-6), and 10(-5) M) followed by KT-5823 (10(-6) M), a cGMP protein kinase inhibitor. Baseline function was similar in young and old myocytes (89.1 +/- 4.5 young vs. 86.4 +/- 8.3 microm/s old R(max), 5.6 +/- 0.3 vs. 5.2 +/- 0.7%shortening). SNAP (10(-5) M) decreased R(max) in both young (25%, n = 6) and old myocytes (24%, n = 7). SNAP also reduced percent shortening by 28% in young and 23% in old myocytes. The negative effects of SNAP were partially reversed by KT-5823 only in young myocytes. Multiple proteins were phosphorylated by cGMP, and KT-5823 could reduce this effect. The degree of phosphorylation was significantly less in old myocytes. These results suggest that the functional response of ventricular myocytes to nitric oxide was preserved during aging. However, the importance of cGMP-dependent protein phosphorylation was decreased, indicating a shift to other pathways.
Zhang
Q
Q
Heart and Brain Circulation Laboratory, Department of Physiology and Biophysics, Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.
Molino
B
B
Yan
L
L
Haim
T
T
Vaks
Y
Y
Scholz
P M
PM
Weiss
H R
HR
D000375:Aging / Q000378:metabolism*; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D002227:Carbazoles; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006352:Heart Ventricles / Q000166:cytology / Q000378:metabolism; D007211:Indoles; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000201:enzymology*; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009929:Organ Size; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010766:Phosphorylation; D011817:Rabbits
D000470:Alkaloids; D002227:Carbazoles; D004791:Enzyme Inhibitors; D007211:Indoles; D020030:Nitric Oxide Donors; C110881:S-nitro-N-acetylpenicillamine; C073601:KT 5823; D009569:Nitric Oxide; D017869:Cyclic GMP-Dependent Protein Kinases; D010396:Penicillamine