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Updated: Aug 23, 2026

Assessment of Vascular Tone Responsiveness using Isolated Mesenteric Arteries with a Focus on Modulation by Perivascular Adipose Tissues
Published on: June 3, 2019
Endothelial venodilator response in carriers of genetic polymorphisms involved in NO synthesis and degradation
Ruth Fricker1, Christiane Hesse, Johanna Weiss
1Department of Internal Medicine VI, Clinical Pharmacology and Pharmacoepidemiology, University of Heidelberg, D-69120 Heidelberg, Germany.
Insights
Genetic variations in NOSIII and CYBA genes do not appear to affect blood vessel function in healthy individuals. This study found no significant link between these gene polymorphisms and endothelial-dependent vasodilation before cardiovascular disease onset.
Area of Science:
- Cardiovascular Genetics
- Vascular Biology
- Molecular Cardiology
Background:
- Polymorphisms in NOSIII and CYBA genes are linked to cardiovascular diseases like hypertension and myocardial infarction.
- Endothelial dysfunction, characterized by impaired vasodilation, is a hallmark of these conditions.
- It is hypothesized that gene variations may influence endothelial function even before clinical manifestation of cardiovascular disease.
Purpose of the Study:
- To investigate whether polymorphisms in the NOSIII and CYBA genes modulate endothelium-dependent vasodilation in healthy individuals.
- To assess the potential role of these gene variations in early endothelial function before overt cardiovascular disease.
Main Methods:
- Endothelium-dependent and -independent venodilation were measured in 72 healthy males using bradykinin and sodium nitroprusside.
- Vascular responses were assessed in the dorsal hand vein after phenylephrine-induced preconstriction.
- Genotyping was performed for NOSIII (T-786C, G894T, (CA)n) and CYBA (C242T) gene polymorphisms.
Main Results:
- No significant differences in venodilator responses to bradykinin or sodium nitroprusside were observed between different genotypes of the studied polymorphisms.
- The number of (CA)n repeat copies in the NOSIII gene did not correlate with bradykinin-induced venodilation.
- Specific genotype carriers showed no significant modulation of venodilation compared to wild-type individuals.
Conclusions:
- The investigated polymorphisms of the NOSIII and CYBA genes do not appear to significantly alter endothelium-dependent venodilation in individuals without known vascular risk factors.
- These findings suggest that these specific genetic variations may not be early indicators of endothelial dysfunction in a healthy population.
Aims:
Polymorphisms of the NOSIII gene and of the CYBA gene have been associated with a number of pathological conditions such as arterial hypertension, coronary artery disease, and myocardial infarction. Because endothelium-dependent vasodilation is impaired in these disorders, we hypothesized that polymorphisms of NOSIII or CYBA might modulate endothelial function of venous capacitance vessels already before cardiovascular disease becomes overt.
Methods:
Endothelium-dependent and -independent venodilation was assessed by measuring local vascular responses to bradykinin and sodium nitroprusside in the dorsal hand vein after preconstriction with phenylephrine in 72 healthy male Caucasians after careful exclusion of cardiovascular risk factors. Genotyping was performed for polymorphisms of the NOSIII gene (T-786C, G894T, (CA)(n)) and the CYBA gene (C242T).
Results:
Genotype distribution for each polymorphism followed the Hardy-Weinberg equilibrium. In all studied single nucleotide polymorphisms no significant difference between the respective genotypes and the venodilator response to either sodium nitroprusside or bradykinin was observed, and the number of CA repeat copies was not related to the venodilator response to bradykinin. Mean venodilation induced by bradykinin 50 ng min(-1) (+/-SEM) for homozygote carriers of the single nucleotide polymorphisms was 48.9 +/- 8.5% venodilation (G894T; wild type: 49.8 +/- 6.9), 50.3 +/- 11.0% venodilation (T-786C; wild type: 42.6 +/- 5.2), and 30.4 +/- 9.1% venodilation (C242T; wild type: 49.2 +/- 6.0), respectively.
Conclusions:
This study suggests that the studied polymorphisms of NOSIII and CYBA do not significantly modulate endothelium-dependent venodilation in individuals without vascular risk factors.
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