The prevalence of atrophic or neovascular age-related macular degeneration is 1.7%. In those 55 years of age or older, the prevalence increases strongly with age and it is similar in men and women. Neovascular age-related macular degeneration was twice as common as atrophic age-related macular degeneration. These findings suggest that age-related maculopathy may be less common in this European population than in similar populations in the United States.

Sympathetic stimulation, at a clinically relevant range, significantly impairs the FMD response by an alpha-adrenergic mechanism.

Abstract-In patients with chronic renal failure (CRF), atherosclerosis is a major cause of cardiovascular morbidity and mortality. Generally, atherosclerosis has been associated with a reduced bioavailability of nitric oxide (NO). Experimental studies have indicated the presence of enhanced NO degradation by reactive oxygen species as well as decreased NO production as possible causes for this reduced NO bioavailability. So far, the question whether or not NO production is impaired in patients with CRF has never been investigated. Therefore, we measured whole body NO production in 7 patients with CRF, and in 7 matched healthy subjects. To assess the relative importance of a dysfunction of NO synthase (NOS), we compared the NO production of these patients to that of 2 other groups known to have endothelial dysfunction, ie, 7 patients with familial hypercholesterolemia (FH) who did not yet have signs of clinical cardiovascular disease (all nonsmokers), and 5 cigarette smokers. These groups were also compared with 7 nonsmoking, age-matched healthy subjects. Whole body NO production, determined as in vivo arginine-to-citrulline conversion, was assessed by giving an intravenous infusion of [ 15 N 2 ]-arginine as a substrate for NOS and measuring isotopic plasma enrichment of [15 N]-citrulline by LC-MS. NO production in the CRF patients (0.13Ϯ0.02 mol ⅐ kg -1 ⅐ h -1 ) was significantly lower (PϽ0.05) than in the corresponding control group (0.23Ϯ0.09 mol ⅐ kg -1 ⅐ h -1 ). NO production also tended to be lower in the FH patients (0.16Ϯ0.04 mol ⅐ kg -1 ⅐ h -1 ), but the difference with the corresponding control group did not reach significance (0.22Ϯ0.06 mol ⅐ kg -1 ⅐ h -1 ). In the group of smokers, NO production was similar to that in nonsmokers (0.22Ϯ0.09 mol ⅐ kg -1 ⅐ h -1 ).In conclusion, it is demonstrated for the first time that basal whole body NO production is reduced in patients with CRF. This finding implies that therapeutic interventions to endothelial dysfunction in these patients should be primarily directed toward improvement of NO production. The finding of only a tendency toward reduction of NO production in patients with FH and the absence of a reduction in cigarette smokers suggests that other mechanisms such as enhanced NO degradation may be involved in the decrease of NO bioavailability in these groups. (Arterioscler Thromb Vasc Biol. 1999;19:1168-1172.) Key Words: nitric oxide Ⅲ chronic renal failure Ⅲ atherosclerosis Ⅲ endothelium Ⅲ hypercholesterolemia P remature atherosclerosis is one of the primary causes of morbidity and mortality in patients with chronic renal insufficiency. 1 Over the last decade endothelial dysfunction has been identified as an early mediator in this process. Nitric oxide (NO) is one of the main factors involved in the antiatherosclerotic effects of the endothelium, 2 and chronic renal failure (CRF) has been associated with impaired NO bioavailability in the absence of concomitant risk factors, [3][4][5] even in children. 6,7 However, the finding of a reduced NO bioavailabi...

Using fluorescence optical and electron spin resonance spectroscopy, we have investigated the production of superoxide by bovine endothelial nitric oxide synthase (NOS). In contrast to neuronal NOS, the heme moiety is identified as the exclusive source of superoxide production by endothelial NOS. Thus, calmodulin-mediated enzyme regulation affects production of nitric oxide and superoxide simultaneously and inseparably. The balance between the nitric oxide/superoxide reaction pathways may be shifted by addition of exogenous heme-specific agents, such as tetrahydrobiopterin. Our results have direct relevance for the pathophysiology of atherosclerosis.z 1998 Federation of European Biochemical Societies.

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