Abstract
Vascular aging is the term that describes the structural and functional disturbances of the vasculature with advancing aging. The molecular mechanisms of aging-associated endothelial dysfunction are complex, but reduced nitric oxide (NO) bioavailability and altered vascular expression and activity of NO synthase (NOS) enzymes have been implicated as major players. Impaired vascular relaxation in aging has been attributed to reduced endothelial NOS (eNOS)-derived NO, while increased inducible NOS (iNOS) expression seems to account for nitrosative stress and disrupted vascular homeostasis. Although eNOS is considered the main source of NO in the vascular endothelium, neuronal NOS (nNOS) also contributes to endothelial cells-derived NO, a mechanism that is reduced in aging. Pharmacological modulation of NO generation and expression/activity of NOS isoforms may represent a therapeutic alternative to prevent the progression of cardiovascular diseases. Accordingly, this review will focus on drugs that modulate NO bioavailability, such as nitrite anions and NO-releasing non-steroidal anti-inflammatory drugs, hormones (dehydroepiandrosterone and estrogen), statins, resveratrol, and folic acid, since they may be useful to treat/to prevent aging-associated vascular dysfunction. The impact of these therapies on life quality in elderly and longevity will be discussed.
Highlights
Many disorders emerge with advancing aging, and cardiovascular diseases (CVD) are a major cause of morbidity and mortality in the elderly1 (Lakatta and Levy, 2003)
Excessive amount of NO produced by inducible nitric oxide synthase up-regulation contributes to vascular dysfunction
The mechanisms by which NO synthase (NOS) enzymes promote vascular dysfunction in aging are specific for each enzyme isoform. endothelial nitric oxide synthase (eNOS) expression and activity are decreased in aging, resulting in reduced NO synthesis
Summary
Many disorders emerge with advancing aging, and cardiovascular diseases (CVD) are a major cause of morbidity and mortality in the elderly (Lakatta and Levy, 2003). The term vascular aging encompasses all the structural and functional alterations in the blood vessels with progressive aging (Herrera et al, 2010) Both smooth muscle cells and intima layers are affected. (Herrera et al, 2010; Seals et al, 2011; Toda, 2011) In this complex scenario, vascular function depends on the balanced production/bioavailability of nitric oxide (NO), which is maintained by the normal activity of endothelial nitric oxide synthase (eNOS). Evidence obtained from experimental models indicates that decreased NO bioavailability as well as increased reactive nitrogen species (RNS) production contributes to aging-associated vascular dysfunction. These effects have been attributed to abnormal expression and activity of vascular NO synthase (NOS) isoforms. INOS is expressed by vascular cells in response www.frontiersin.org
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