Supine hypertension is found in up to 50% of patients w/severe autonomic failure. This hypertension could be explained by an increase in intravascular volume, an increase in cardiac output, an increase in vascular tone, or a combination of these mechanisms. It has been reported previously that patients w/autonomic failure have a normal intravascular volume. It has also been shown that cardiac output is not increased in patients w/autonomic failure compared w/normal control subjects. On the other hand, previous studies have shown that supine hypertension in patients w/autonomic failure is characterized by increased systemic vascular resistance. However, the mechanisms increasing systemic vascular resistance in the face of low plasma norepinephrine and plasma renin activity are not known. Over the past few years a non-adrenergic non-cholinergic mechanism, which includes nitric oxide (NO), has emerged as an important regulatory mechanism of vasomotor tone. NO is a potent vasodilator and is synthesized from the amino acid L-arginine by the enzyme NO synthase. Reduced NO synthesis remains a possibility that increases vascular tone in patients w/autonomic failure. NO synthesis can be experimentally blocked by a competitive stereospecific inhibitor of NO synthase, N-monomethyl-L-arginine (L-NMMA), which provides an important tool to investigate the relevance of NO in biologic processes. The main purpose of the present investigation is to determine whether a reduced NO synthase activity is present and whether this reduction increases peripheral vascular resistance in patients w/autonomic failure.
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