Which diseases are associated with elevated ADMA blood levels?

Elevated ADMA concentrations have been measured in numerous cardiovascular and metabolic diseases, e.g. in coronary artery disease, congestive heart failure, peripheral arterial occlusive disease, hypercholesterolemia, hypertension, diabetes mellitus, and others (Table 1).

Recently a close correlation was reported between ADMA and the presence of insulin resistance. This finding may point to a possible involvement of ADMA in the pathophysiology of the metabolic syndrome.
Erectile dysfunction is yet another disease which has been linked to a functional defect in the NO pathway. NO is an essential messenger which causes dilatation of penile erectile tissue, resulting in an erection. This occurs only when psychogenic sexual stimulation is present, which causes local NO release from penile nitrinergic nerve endings. In the presence of elevated ADMA levels, NO synthase is unable to adequately respond to sexual stimuli with NO production, and the erection is impaired or lacking - erectile dysfunction occurs. Substances like phosphodiesterase V inhibitors (sildenafil and similar compounds) inhibit the degradation of cyclic GMP, the second messenger molecule that mediates many of the biological actions of NO (Figure 12).

Figure 11. NO physiologically induces the formation of the intracelllular second messenger, cyclic GMP. This causes relaxation of vascular smooth muscle cells and is therefore the cause for hypotension and penile erection. In the presence of elevated ADMA levels, these functions are impaire. PDE V inhibitors inhibit the degradation of cyclic GMP and thereby can amplify the actions of NO (which, however, are reduced in the presence of ADMA).

The diseases listed in Table 1 that have been shown to be associated with elevated ADMA levels are all characterized by endothelial dysfunction. In some of them, determination of ADMA levels has been shown to be of prognostic importance for predicting the incidence of major cardiovascular events (as detailed below).