Myocyte function and [Ca 2+ ]i homeostasis during early allogenic heart transplant rejection.
BACKGROUND
Recent studies from our laboratory have demonstrated that in vivo contractile function of rejecting mouse heterotopic abdominal heart allografts 5 days after transplantation is depressed to 40% of that of syngenic controls, and that this depression of function is prevented by the nitric oxide synthase (NOS) inhibitor NG-monomethyl-l-arginine. However, the mechanisms of altered myocyte function caused by nitric oxide production in this setting are not established.


METHODS
We measured intracellular calcium concentration ([Ca2+]i) transients (fluo-3, confocal microscopy), fractional shortening (video motion), and L-type Ca2+ currents (whole-cell patch clamp) 5 days after transplantation in ventricular myocytes freshly isolated from syngenic (Balb/C into Balb/C) and allogenic (Balb/C into C3H) transplants.


RESULTS
L-type Ca2+ currents, [Ca2+]i transient amplitudes, and fractional shortening did not differ between nonrejecting, syngenic and rejecting, allogenic transplants. Catecholamine responsiveness as analyzed by the change in the peak [Ca2+]i transient induced by 100 nM isoproterenol was also similar. Superfusion with l-arginine, an NOS substrate, caused decreased shortening with no change in [Ca2+]i transients in allogenic myocytes, but had no effect in syngenic myocytes.


CONCLUSIONS
Depressed contractile function of rejecting allogenic heart transplants in vivo appears to be caused in part by an NOS-dependent decrease in myofilament Ca2+ sensitivity.
Ritter
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M
Division of Cardiology, University of Utah Health Sciences Center, 50 North Medical Drive, Salt Lake City, UT 84132, USA.
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Yao
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Zubair
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Shelby
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Barry
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D000818:Animals; D001120:Arginine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D006152:Cyclic GMP / Q000502:physiology; D006084:Graft Rejection / Q000503:physiopathology*; D016027:Heart Transplantation / Q000276:immunology*; D006706:Homeostasis; D007545:Isoproterenol / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D009200:Myocardial Contraction / Q000187:drug effects*; D019001:Nitric Oxide Synthase / Q000502:physiology; D014184:Transplantation, Homologous
D001120:Arginine; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP; D007545:Isoproterenol; D002118:Calcium