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Nitric oxide: not just a negative inotrope
Author(s) -
Sarkar David,
Vallance Patrick,
Harding Sian E.
Publication year - 2001
Publication title -
european journal of heart failure
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.149
H-Index - 133
eISSN - 1879-0844
pISSN - 1388-9842
DOI - 10.1016/s1388-9842(01)00163-5
Subject(s) - inotrope , nitric oxide , nitric oxide synthase , myocyte , medicine , cardiac function curve , downregulation and upregulation , gene isoform , pharmacology , heart failure , cardiac myocyte , endogeny , effector , microbiology and biotechnology , chemistry , biology , biochemistry , immunology , gene
Nitric oxide (NO) appears to play a role in modulating cardiac function in both health and disease. Early studies in isolated rodent cardiac myocytes demonstrated a depressant effect of NO supplied by NO donors (exogenous) as well as NO generated within myocytes (endogenous). There is increasing evidence for a functional NO generating system within the human myocardium, which appears upregulated in certain disease states. Induction of the high output nitric oxide synthase isoform (iNOS) has been demonstrated in the failing myocardium, though its functional significance remains unproven. More recently published data have contradicted the notion that NO acts solely as a negative inotrope demonstrating positive inotropy in both isolated rodent and human ventricular myocytes in response to a range of NO donors. Different NO donors have different NO release kinetics and generate a range of NO species (NO · , NO + and NO − ) which may interact at a number of subcellular targets. The observed response of any cardiac preparation to an NO donor represents the net effect of activation of different effector targets and may explain the contradictory reported effects of NO. To realise the therapeutic potential of NO will require specific targeting at a subcellular level.