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Updated: Aug 19, 2026

Measurement of Cyclic Guanosine Monophosphate (cGMP) in Solid Tissues using Competitive Enzyme-Linked Immunosorbent Assay (ELISA)
Published on: July 3, 2025
Relationship between urinary cGMP excretion and serum total cholesterol levels in a general population
Renzhe Cui1, Hiroyasu Iso, Jingbo Pi
1Department 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.
Insights
High cholesterol impairs blood vessel function. This study found that higher total cholesterol levels, even within normal ranges, correlate with reduced nitric oxide (NO) bioactivity, indicated by lower urinary cyclic guanosine 3
Area of Science:
- Cardiovascular Science
- Endocrinology
- Nephrology
Background:
- Hypercholesterolemia is known to impair endothelial function, a critical component of cardiovascular health.
- The specific threshold of serum total cholesterol at which endothelial dysfunction initiates remains undetermined.
- Nitric oxide (NO) plays a vital role in maintaining endothelial function, and its bioactivity can be assessed via its second messenger, cyclic guanosine 3',5' monophosphate (cGMP).
Purpose of the Study:
- To investigate the relationship between serum total cholesterol concentrations and urinary cGMP excretion in a general Japanese population.
- To determine if elevated cholesterol levels, even within clinically normal ranges, are associated with reduced NO bioactivity.
Main Methods:
- Cross-sectional study involving 1541 Japanese men and women aged 40-79 years.
- Collected 24-hour urine samples to measure urinary cGMP excretion, adjusted for urinary creatinine.
- Assessed serum total cholesterol levels and adjusted for age, sex, and cardiovascular risk factors.
Main Results:
- A significant inverse linear correlation was observed between serum total cholesterol levels and urinary cGMP excretion (p=0.007).
- Mean urinary cGMP excretion decreased progressively with increasing total cholesterol levels, starting from <4.14 mmol/L.
- This inverse relationship was more pronounced in individuals with end-organ damage, higher C-reactive protein (CRP) levels, and postmenopausal women.
Conclusions:
- Higher serum total cholesterol levels are associated with reduced nitric oxide bioactivity, even within clinically normal ranges.
- This finding suggests a potential mechanism for endothelial dysfunction in hypercholesterolemia that may begin at lower cholesterol levels than previously thought.
- Further research is warranted to elucidate the clinical implications of reduced NO bioactivity at varying cholesterol levels.
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.
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