Methods and Findings in Experimental and Clinical Pharmacology
Vol. 24, Suppl. A, 2002, pp. 63-64
ISSN 0379-0355
Copyright 2002 Prous Science, S.A.
CCC: 0379-0355/2002
http://www.prous.com

Aging and the Vascular Wall

L. Rodríguez Mañas

Servicio de Geriatría. Unidad de Investigación. Hospital Universitario de Getafe.

One of the systems classically affected by the aging process is the vascular process. According to data from the WHO, the diseases of the cardiovascular system are, and will be over the next few years, the first cause of death, disability and dependency in the world (1). Moreover, recent data from the Cardiovascular Health Study have shown that subclinical impairments in the cardiovascular system are the best predictors for the developing of frailty in elderly people (2). Thus, to study the mechanisms involved in the beginning, development and clinical manifestations of the impairment of the cardiovascular system holds a pivotal role in the research agenda of aging. Much of the data published during recent years suggest that the endothelium plays a significant role in the changes associated with aging of the
cardiovascular system (3, 4). This fact is relevant because endothelial dysfunction can be observed several years before the appearance of the clinically relevant vascular disease (5). The presence of endothelial dysfunction related to an impairment in the NO-mediated and prostaglandin-mediated mechanisms is one of the main conclusions arising from studies carried out in animal models of aging. The causes for such impairment are not well known. Experimental data from our own group in human microvessels show that during human aging, a loss of the relaxation mediated by prostacyclin occurs, and this is accompanied by an impairment of the NO-mediated response. Moreover, this impairment in NO-induced vasodilatation is due to the presence of extracellular superoxide and a derivative of cyclooxigenase acting in a complementary way (6).

VASCULAR AGING ­ AN OXIDATIVE PROCESS?

Free radicals are involved in the general mechanism of aging and in the genesis of the vascular damage associated with diseases such as diabetes, hyperlypoproteinemia or atherosclerosis (7). Some data in animal models suggest changes in the expression and activity of the NO synthases that accompany the aging process (8). These changes consist in a decreased activity of endothelial NOS and an increased activity in the inducible isoform of the enzyme. Preliminary data obtained in our lab in human endothelial cells support this finding previously observed only in animals (9). It is possible that oxidative stress will be involved in producing these changes by means of transcription factors (NF-kB, AP-1) (10). Finally, oxidative stress may impair the vasodilatation induced by interaction with NO, produce peroxynitrite or indeed contribute to the uncoupling of NO synthase (11).

VASCULAR AGING ­ AN INFLAMMATORY PROCESS?

Many studies have connected the aging process with an increase in some cytokines (12). Moreover, an increase in COX activity in the aorta and mesenteric vessels of aged rats has been shown (8). Our data show that in human microvessels, there is a loss of the relaxation induced by prostacyclin together with the release of a COX-dependent vasoconstrictor substance (13), although we have not yet identified the isoenzyme responsible for these effects (COX-1/COX-2). It is also possible that an increased mRNA activity exits for several inflammation mediators (9).

REFERENCES

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13. Vallejo, S., Sánchez Ferrer, A., Giorgi, M.G. et al. Components of the aging-associated endothelial dysfunction in human mesenteric microvessels. XVIIth World Congress of the International Association of Gerontology: Vancouver, July 1-6, 2001.

Methods and Findings in Experimental and Clinical Pharmacology Vol. 24, Suppl. A, 2002, pp. 63-64
ISSN 0379-0355 Copyright 2002 Prous Science, S.A. CCC: 0379-0355/2002 http://www.prous.com