Inducible Nitric Oxide Synthase as a Possible Target in Hypertension
Gustavo H. Oliveira-Paula, Riccardo Lacchini and Jose E. Tanus-Santos
Affiliation: Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Av. Bandeirantes, 3900, 14049-900 Ribeirao Preto, SP, Brazil.
Keywords: Endothelial dysfunction, hypertension, inducible nitric oxide synthase, inducible nitric oxide synthase inhibition,
Nitric oxide (NO) is an important vasodilator produced by vascular endothelium. Its enzymatic formation is derived
from three different synthases: neuronal (nNOS), endothelial (eNOS) and inducible (iNOS) synthases. While relatively
small amounts of NO produced by eNOS are important to cardiovascular homeostasis, high NO levels produced associated
with iNOS activity may have detrimental consequences to the cardiovascular system and contribute to hypertension.
In this article, we reviewed current literature and found mounting evidence indicating that increased iNOS expression
and activity contribute to the pathogenesis of hypertension and its complications. Excessive amounts of NO produced
by iNOS up-regulation can react with superoxide anions forming peroxynitrite, thereby promoting nitrosative stress and
endothelial dysfunction. In addition, abnormal iNOS activity can up-regulate arginase activity, allowing it to compete with
eNOS for L-arginine, thereby resulting in reduced NO bioavailability. This may also lead to eNOS uncoupling with enhanced
production of superoxide anions instead of NO. All these alterations mediated by iNOS apparently contribute to
hypertension and its complications. We also reviewed current evidence showing the effects of iNOS inhibitors on different
animal models of hypertension. iNOS inhibition apparently exerts antihypertensive effects, decreases oxidative and nitrosative
stress, and improves vascular function. Together, these studies highlight the possibility that iNOS is a potential
pharmacological target in hypertension.
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