Inflammatory cell-derived NO modulates cardiac allograft contractile and electrophysiological function

Autor: R. T. Pyo, T. B. Ferguson, T. P. Misko, M D Botney, D. G. Alexander, P. M. Sullivan, N. K. Worrall, W. D. Lazenby
Rok vydání: 1997
Předmět:
Male
medicine.medical_specialty
Transplantation
Heterotopic
Transcription
Genetic
Physiology
Heart Ventricles
Action Potentials
In Vitro Techniques
Biology
Pharmacology
Nitric Oxide
Guanidines
Methylprednisolone
Membrane Potentials
Nitric oxide
Contractility
chemistry.chemical_compound
Adrenal Cortex Hormones
Heart Rate
Physiology (medical)
Internal medicine
medicine
Animals
Transplantation
Homologous
RNA
Messenger
Cells
Cultured
ATP synthase
Cardiac allograft
RNA Probes
Papillary Muscles
Myocardial Contraction
Rats
Rats
Inbred ACI
Electrophysiology
Transplantation
Nitric oxide synthase
Transplantation
Isogeneic
Endocrinology
chemistry
Rats
Inbred Lew
biology.protein
Heart Transplantation
Calcium
Nitric Oxide Synthase
Cardiology and Cardiovascular Medicine
Function (biology)
Adenylyl Cyclases
Zdroj: Scopus-Elsevier
ISSN: 1522-1539
0363-6135
DOI: 10.1152/ajpheart.1997.273.1.h28
Popis: We previously demonstrated that inhibition of inducible nitric oxide (NO) synthase (iNOS) ameliorated acute cardiac allograft rejection. This study used a rat cardiac transplant model to characterize contractile and electrophysiological dysfunction during early acute rejection, further examine the role of NO and iNOS in this process, and determine which cells expressed iNOS during early rejection. During early acute rejection, before significant myocyte necrosis, allograft papillary muscles had reduced tension development and rates of tension development and decline during beta-adrenergic, adenylate cyclase, and calcium stimulation compared with isograft and normals [e.g., tension of 36 (allograft) vs. 73 (isograft) mN/mm2 during calcium stimulation, P< 0.001]. Allografts had resting membrane potential depolarization and reduced action potential amplitude and upstroke velocity. iNOS mRNA was expressed in infiltrating inflammatory cells but not in allograft myocytes, endothelial cells, or isografts. Corticosteroids attenuated allograft contractile and electrophysiological dysfunction and inhibited iNOS enzyme activity. Direct iNOS inhibition with aminoguanidine inhibited NO production and prevented allograft contractile and electrophysiological dysfunction (e.g., tension of 64 mN/mm2 during calcium stimulation, P < 0.001). We conclude that 1) early allograft rejection caused contractile and electrophysiological dysfunction that was largely mediated by iNOS expression in infiltrating inflammatory cells, 2) corticosteroid-mediated amelioration of allograft contractile and electrophysiological dysfunction may reflect inhibition of iNOS, and 3) iNOS inhibition may offer an alternative in management of immune-mediated myocardial dysfunction.
Databáze: OpenAIRE
Externí odkaz: