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      An Intron 4 Gene Polymorphism in Endothelial Cell Nitric Oxide Synthase Might Modulate Volume-Dependent Hypertension in Patients on Hemodialysis


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          Nitric oxide (NO) has some relevance to the pathophysiology of hypertension. We examined the distribution of endothelial nitric oxide synthase (ecNOS4) gene polymorphism in patients with essential hypertension (n = 107) in comparison with healthy subjects (n = 362), and then studied the possibility that ecNOS4 gene polymorphism affects changes in blood pressure (BP) due to water load in hemodialysis patients. Though the NO metabolite (NOx) level in subjects with the a allele (31.2 ± 1.76 µmol/l) was significantly lower than in those without the a allele (35.6 ± 0.90 µmol/l) (p = 0.0263), we found no association between this gene polymorphism and essential hypertension. However, there still remains the possibility that the NO response to elevation of BP might be suppressed in patients with hypertension. In order to examine the association between ecNOS4 gene polymorphism and volume-dependent hypertension, 181 hemodialysis patients with complete anuria were recruited. Depending on the increase in mean BP (mm Hg) divided by percent increase in body weight (ΔBP/ΔBW), patients were divided into high responders (High-R: ΔBP/ΔBW >2.0 mm Hg; n = 90) and low responders (Low-R: ΔBP/ΔBW <2.0 mm Hg; n = 91). In the High-R group, the frequencies of a/a, b/a and b/b genotypes were 1.1, 32.1 and 66.8%, respectively, and in the Low-R group, these frequencies were 1.1, 9.4 and 89.5%, respectively. The relative risk for those in the High-R group conferred by the ecNOS4 a allele ( b/a + a/a) was 3.64 (95% confidence intervals: 1.60–8.24, p = 0.0089). This study did not show a strong involvement of ecNOS4 gene polymorphism, at least in the basal NO production in patients with essential hypertension, however, it indicated that ecNOS4 gene polymorphism might modulate changes in BP due to water load in patients on hemodialysis, thus indicating that these polymorphisms may be involved in the pathophysiology of volume-dependent hypertension.

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          Most cited references3

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          NO at work

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            High Accumulation of Endothelial Nitric Oxide Synthase (ecNOS):A Gene Polymorphism in Patients with End-Stage Renal Disease

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              Activation of Nitric Oxide Synthesis in Vascular Smooth Muscle Cells and Macrophages During Development in Spontaneously Hypertensive Rats

              X JIN (1996)

                Author and article information

                S. Karger AG
                July 2000
                21 June 2000
                : 85
                : 3
                : 232-237
                aInternal Medicine II, Jikei University School of Medicine; bDepartment of Clinical Chemistry, and cKidney Center, Toranomon Hospital, Tokyo, Japan
                45666 Nephron 2000;85:232–237
                © 2000 S. Karger AG, Basel

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                Page count
                Figures: 2, Tables: 4, References: 22, Pages: 6
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                Self URI (journal page): https://www.karger.com/SubjectArea/Nephrology
                Original Paper

                Cardiovascular Medicine,Nephrology
                Plasma nitrite and nitrate,Blood pressure,Endothelial nitric oxide synthase,DNA polymorphism,Hemodialysis


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