Role of Nitric Oxide in Cardiovascular Disorders - Applications of Biotechnology in Cardiovascular Therapeutics - page 80

Role of NO in Management of Cardiovascular Disorders
Cardiovascular mechanisms of action of various classes of NO-modulating agents
have been reviewed in earlier sections. Cardiovascular disorders for which
NO-based therapies are used are listed in Table 3.1 . Cardioprotective effect of NO
will be considered in this section.
Role of NO in Cardioprotection
NO, either endogenous or exogenous, represents one of the most important defenses
against myocardial ischemia-reperfusion injury. In the cardioprotective actions of NO,
iNOS and mitochondria play an import role. The protective action of NO may be
achieved through ischemic preconditioning, pharmacological cardioprotection, and
gene therapy. The late phase of preconditioning is mediated by increased iNOS activity
resulting in enhanced NO bioavailability. Various drugs (e.g., statins, ACE inhibitors,
angiotensin-receptor blockers, etc.) also produce salubrious effects in experimental
models of myocardial infarction via their enhancement of NO bioavailability. Thus,
NO appears to be a common mediator of the protection afforded by a wide array of
seemingly unrelated pharmacological and nonpharmacological interventions, under-
scoring its fundamental role as a ubiquitous defense of the heart against ischemia and
reperfusion. This challenges the conventional wisdom that iNOS is deleterious during
myocardial ischemia-reperfusion and instead proposes the concept that iNOS, when
expressed in cardiac myocytes, is a profoundly protective protein. Although the precise
molecular events remain to be defined, NO interacts with components of the electron
transport chain and/or the mitochondrial permeability transition pore to limit postisch-
emic myocardial damage, and this action potentially provides a fundamental molecu-
lar explanation for the mechanism of NO-mediated cardioprotection.
Ischemic reperfusion injury (IRI) occurs frequently in revascularization proce-
dures such as coronary artery bypass graft (CABG). Conditioning of myocardial
cells to an oxidative stress prior to IRI may limit the consequences of this injury.
Preconditioning the myocardium with hyperbaric oxygen (HBO) before reperfusion
has been shown to have a myocardial protective effect by limiting the infarct size
Table 3.1 Cardiovascular disorders for which NO-based therapies are used
Atherosclerosis
Coronary heart disease/myocardial ischemia
Angina pectoris
Myocardial infarction
Adjunct therapy to coronary artery bypass graft (CABG)
Coronary artery restenosis
Congestive heart failure
Hypertension
Hypercholesterolemia
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