NOS1 and heart failure: Patterns of myocardial NO signalling can undergo changes in heart failure,67–69 hypertension,70 and ischaemia/reperfusion injury68,71,72 as a result of altered NOS isoform expression67,68,70,71 and subcellular distribution67,68 or abnormal intracellular chemistry (e.g. NO scavengers73 and NOS co-factors19) In failing hearts, for instance, raised nNOS activity at the sarcolemma67,68 may produce a more intensive release of NO near NHE1, potentially resulting in inhibition.