title: Relationship between urinary cGMP excretion and serum total cholesterol levels in a general population.
abstract: Hypercholesterolemia impairs endothelial function. However, the critical level of serum total cholesterol at which endothelial dysfunction occurs is unknown at present. We investigated cross-sectionally the correlation between urinary excretion of cyclic guanosine 3',5' monophosphate (cGMP), a second messenger of nitric oxide (NO) and serum total cholesterol concentrations in a general population sample of Japanese men and women. The samples comprised 1541 subjects (788 men and 753 women) aged 40-79 years, who participated in cardiovascular risk surveys between 1997 and 2002 and underwent a 24h urine collection. Urinary excretion of cGMP was measured using a (125)I-labeled cGMP radioimmunoassay and was adjusted for urinary creatinine excretion (nmol/mmol creatinine). The mean urinary cGMP excretion correlated linearly and inversely with serum total cholesterol level: mean cGMP excretion adjusted for age, sex and cardiovascular risk factors was 61.7, 53.6, 50.8, 49.2, 47.3 and 46.4 nmol/mmol for total cholesterol levels <4.14, 4.14-4.64, 4.65-5.16, 5.17-5.68, 5.69-6.20 and > or =6.21 mmol/L, respectively (p=0.007). This relation was more evident among individuals with end-organ damage, among subjects with higher C-reactive protein (CRP) levels and among postmenopausal women. Our data suggest a reduction of NO bioactivity with higher serum total cholesterol levels, even within clinically normal cholesterol levels.
authors.affiliation: Department of Public Health, Social and Environmental Medicine, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Renzhe
authors.initials: R
authors.lastname: Cui
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Iso
authors.forename: Jingbo
authors.initials: J
authors.lastname: Pi
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Kumagai
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Yamagishi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tanigawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Shimamoto
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D002784:Cholesterol / Q000097:blood*; D003430:Cross-Sectional Studies; D006152:Cyclic GMP / Q000652:urine*; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000473:pathology*; D008297:Male; D008593:Menopause; D008875:Middle Aged; D009569:Nitric Oxide / Q000032:analysis*; D012016:Reference Values; D015290:Second Messenger Systems; D012737:Sex Factors
chemical_list: D009569:Nitric Oxide; D002784:Cholesterol; D006152:Cyclic GMP