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Expression and Activity Patterns of Nitric Oxide Synthases and Antioxidant Enzymes Reveal a Substantial Heterogeneity Between Cardiac and Vascular Aging in the Rat

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Abstract

We investigated the effects of aging and ischemia–reperfusion (I/R) injury on the expression and activity of nitric oxide (•NO) synthases and superoxide dismutase (SOD) isoforms. To this end we perfused excised hearts from young (6 months old) and old (31–34 months old) rats according to the Langendorff technique. The isolated hearts were, after baseline perfusion for 30 min, either subjected to 20 min of global no-flow ischemia followed by 40 min of reperfusion or were control-perfused (60 min normoxic perfusion). Both MnSOD and Cu,ZnSOD expression remained unchanged with increasing age and remained unaltered by I/R. However, SOD activity decreased from 7.55 ± 0.1 U/mg protein in young hearts to 5.94 ± 0.44 in old hearts (P<0.05). Furthermore, I/R led to a further decrease in enzyme activity (to 6.35 ± 0.41 U/mg protein; P<0.05) in myocardium of young, but not in that of old animals. No changes in myocardial protein-bound 3-nitrotyrosine levels could be detected. Endothelial NOS (eNOS) expression and activity remained unchanged in aged left ventricles, irrespective of I/R injury. This was in steep contrast to peripheral (renal and femoral) arteries obtained from the same animals where a marked age-associated increase of eNOS protein expression could be demonstrated. Inducible NOS expression was undetectable either in the peripheral arteries or in the left ventricle, irrespective of age. In particular when associated with an acute pathology, which is furthermore limited to a certain time frame, changes in the aged myocardium with respect to enzymes crucially involved in maintaining the redox homeostasis, seem to be much less pronounced or even absent compared to the vascular aging process. This may point to heterogeneity in the molecular regulation of the cardiovascular aging process.

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Abbreviations

SOD:

superoxide dismutase

PGI2 :

prostacyclin

•NO:

nitric oxide

eNOS:

endothelial nitric oxide synthase (NOS III)

iNOS:

inducible nitric oxide synthase (NOS II)

COX:

cyclooxygenase

•O −2 :

superoxide

LVDP:

left ventricular developed pressure

P:

perfusion

I:

ischemia

Y:

young

O:

old

I/R:

ischemia/reperfusion

Mn:

manganese

Cu,Zn:

copper, zinc

cGMP:

cyclic guanosine monophosphate

GSH:

glutathione

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Authors and Affiliations

  1. Division of Cardiology, Cardiovascular Centre, University Hospital Zurich, Rämistrasse 100, CH-8091, Zürich, Switzerland

    Bernd van der Loo, Juliane Kilo & Thomas F. Lüscher

  2. Department of Biology, University of Konstanz, Konstanz, Germany

    Markus Bachschmid, Stefan Schildknecht & Raphael Hahn

  3. Division of Cardiovascular Research, Institute of Physiology, University Zurich-Irchel, Switzerland

    Ralf Labugger & Thomas F. Lüscher

  4. Wolfson Institute for Biomedical Research, University College London, UK

    Miriam Palacios-Callender

Authors
  1. Bernd van der Loo
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  2. Markus Bachschmid
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  3. Ralf Labugger
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  4. Stefan Schildknecht
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  5. Juliane Kilo
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  6. Raphael Hahn
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  7. Miriam Palacios-Callender
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  8. Thomas F. Lüscher
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Correspondence to Thomas F. Lüscher.

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van der Loo, B., Bachschmid, M., Labugger, R. et al. Expression and Activity Patterns of Nitric Oxide Synthases and Antioxidant Enzymes Reveal a Substantial Heterogeneity Between Cardiac and Vascular Aging in the Rat. Biogerontology 6, 325–334 (2005). https://doi.org/10.1007/s10522-005-4807-1

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