Partial inhibition of nitric oxide synthase primes the stimulated pathway of vWF-secretion in man.
Atherosclerosis
; 148(1): 43-7, 2000 Jan.
Article
em En
| MEDLINE
| ID: mdl-10580169
ABSTRACT
Increased release of von Willebrand factor (vWF) has been linked to the pathogenesis of atherosclerosis. For this complex disease, impairment of endothelium-derived, nitric oxide production and impaired vascular relaxation has also been reported. Since endothelially produced nitric oxide (NO) is known to inhibit secretion of the Weibel-Palade bodies in animals, we hypothesized that NO could mitigate vWF secretion. In a randomized, placebo controlled cross-over trial, eight male volunteers received N-monomethyl-L-arginine (LNMMA) to block endothelial NO production or placebo, and vWF release was stimulated by infusing desmopressin in three cumulative doses (0.05, 0.15, 0.4 microg/kg) in both periods. At a threshold dose of 0.l5 microg/kg desmopressin, concomitant partial blockade of NO production resulted in 20% higher levels of vWF (P<0.04). However, maximal vWF release after 0.4 microg/kg desmopressin was unaffected by L-NMMA (Delta7% between periods, P=0.88). These data show the dampening effect of NO production on vWF release in response to threshold concentrations of secretagogues. This may in part explain the higher vWF levels in cardiovascular diseases associated with impaired endothelial NO generation.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fator de von Willebrand
/
Óxido Nítrico Sintase
Tipo de estudo:
Clinical_trials
Limite:
Adult
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2000
Tipo de documento:
Article