BACKGROUND: Cardiovascular disease induces erectile dysfunction modulated by endothelial nitric oxide synthase enzyme and an impaired ejection fraction that restricts penis vascular congestion. However, the mechanisms regulating endothelial dysfunction are not understood.
OBJECTIVE: Exploring the functional impact of endothelial nitric oxide synthase genetic polymorphisms on erectile dysfunction and drug therapy optimization in high-risk cardiovascular disease patients.
METHODS: Patients with erectile dysfunction symptoms and candidates for andrology therapy were included (n = 112). Clinical data and endothelial nitric oxide synthase rs1799983 (G894T) and rs2070744 (T-786C), genotyped by fluorescence polarization assays, were registered. The 27-bp variable number of the tandem repeat polymorphism in intron 4 (intron4b/a) was analyzed by polymerase chain reaction-restriction fragment length polymorphism. Association analyses were run with the R-3.2.0 software.
RESULTS: A significant association between endothelial nitric oxide synthase 786-TT (p = 0.005) and the aa/ac of intron 4 variable number of the tandem repeat (p = 0.02) with higher erectile dysfunction susceptibility was observed in cardiovascular disease patients (60 ± 9 years, 66% severe erectile dysfunction, 56% ejection fraction). After 3-months of phosphodiesterase type 5 inhibitors, erectile dysfunction (International Index of Erectile Function, 50 ± 16 scores, the International Index of Erectile Function-Erectile Function 21 ± 10 scores, p < 0.001) and sexual quality of life (modified Sexual Life Quality Questionnaire 55 ± 23 scores, p < 0.001) had significantly improved. The cardiovascular ejection fraction was influenced positively with better sexual quality of life (0.1941), and also in the endothelial nitric oxide synthase G894-T allele (p = 0.076) carriers, which could merit future analyses. Erectile dysfunction was present as the primary clinical manifestation in 62% of cases, with cardiovascular disease occurring concurrently. Only former smokers and obese subjects debuted prior to cardiovascular disease than to erectile dysfunction.
CONCLUSIONS: Our study provides comprehensive insights into the functional interaction linking endothelial nitric oxide synthase gene polymorphisms, erectile function, and ejection fraction in high-risk cardiovascular disease patients. Future therapeutic strategies could target endothelial nitric oxide synthase activity by including lifestyle changes and epigenetic modulations.

BACKGROUND: Nitric oxide (NO) exerts diverse effects on the cardiovascular system. Impairment of NO production plays a key role in cerebral and coronary artery spasm. We aimed to explore the predicting factors of radial artery spasm (RAS) and the association of eNOS gene polymorphism (Glu298Asp) with RAS during cardiac catheterization.
RESULTS: 200 patients underwent elective coronary angiography through a trans-radial approach. The subjects were genotyped to the Glu298Asp polymorphism (rs1799983) on the eNOS gene by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Our results showed that the subjects with the TT genotype and T allele were significantly more likely to develop radial artery spasms (OR = 12.5, 4.6, P < 0.001 respectively). TT genotype of eNOS Glu298Asp polymorphism, number of punctures, size of the radial sheath, radial tortuosity, and right radial access are independent predictors of radial spasm.
CONCLUSIONS: The eNOS (Glu298Asp) gene polymorphism is associated with RAS during cardiac catheterization in Egyptians. TT genotype of eNOS Glu298Asp polymorphism, number of punctures, size of the radial sheath, right radial access, and tortuosity are independent predictors of RAS during cardiac catheterization.

To detect eNOS gene polymorphism and its relation to cardiovascular complications in pediatric acute lymphoblastic leukemia (ALL) survivors.
CBC, renal and liver function tests, lipid profile, Carotid artery Intima Media Thickness (CIMT), and Brachial artery Intima Media Thickness (BIMT). eNOS gene polymorphism was done in 40 childhood ALL survivors and 40 controls.
There was no significant difference between survivors and control groups regarding 786 T/C polymorphism. There was a significant increase in serum cholesterol, TGs, LDL, VLDL, and HbA1c in the TC and CC group more than in the TT group, while there was a significant decrease in serum HDL in the TC and CC group more than in the TT group. There was no significant difference as regards echocardiography findings between different polymorphisms of 786 T/C, but there was a significant difference between 786 T/C groups with regard to the carotid and brachial arteries intima media thickness (IMT) measurements being significantly higher in the TC and CC group more than in the TT group.
Carotid and brachial arteries intima media thickness measurements were higher in the survivors when compared to healthy controls. eNOS gene polymorphism may play a role in modifying or developing CVD in pediatric ALL survivors.

Endothelial nitric oxide synthase (eNOS) plays a critical role in regulating and maintaining a healthy cardiovascular system. The importance of eNOS can be emphasized from the genetic polymorphisms of the eNOS gene, uncoupling of eNOS dimerization, and its numerous signaling regulations. The activity of eNOS on the cardiac myocytes, vasculature, and the central nervous system are discussed. The effects of eNOS on the sympathetic autonomic nervous system (SANS) and the parasympathetic autonomic nervous system (PANS), both of which profoundly influence the cardiovascular system, will be elaborated. The relationship between the eNOS protein with cardiovascular autonomic reflexes such as the baroreflex and the Exercise Pressor Reflex will be discussed. For example, the effects of endogenous nitric oxide (NO) are shown to be mediated by the eNOS protein and that eNOS-derived endothelial NO is most effective in regulating blood pressure oscillations via modulating the baroreflex mechanisms. The protective action of eNOS on the CVS is emphasized here because dysfunction of the eNOS enzyme is intricately correlated with the pathogenesis of several cardiovascular diseases such as hypertension, arteriosclerosis, myocardial infarction, and stroke. Overall, our current understanding of the eNOS protein with a focus on its role in the modulation, regulation, and control of the cardiovascular system in a normal physiological state and in cardiovascular diseases are discussed.

OBJECTIVE: To investigate whether endothelial nitric oxide synthase (eNOS) T786C, 4VNTR and G894 T gene polymorphisms could mediate in andrological treatment response in Spaniards.
UNASSIGNED: The study participants were Spaniard males with erectile dysfunction (ED) and chronic pain (n = 105) recruited at the Pain Unit. eNOS polymorphisms were genotyped by quantitative polymerase chain reaction using Taqman specific probes. Statistical analyses were carried out using R-3.2.4 software.
RESULTS: A total of 69 patients required andrological treatment and 76% of them improved ED upon iPED5 (20%), testosterone (35%) or iPDE5/testosterone treatment (45%); being significantly better in T786C-CC patients. Multivariate regression analysis indicated that age, opioid daily dose and carriage of T786C-C allele influenced the risk and ED severity in Spaniard chronic pain patients.
CONCLUSIONS: T786C polymorphism at eNOS locus appeared to be a major contributor in the variable erectile function iPDE5/testosterone response in Spaniards.

The association between erectile dysfunction (ED) and cardiovascular disease (CVD) is well known, the latter being an early independent risk factor that can appear up to 5 years before the onset of cardiovascular symptoms. The enzyme endothelial nitric oxide synthase (eNOS) could be implicated in its pathophysiology as an endogenous vasodilator. Our objective was to analyse the influence of variants of the eNOS gene, in the response to treatment of ED, in patients with CVD.
Observational, prospective study in patients with ED of the Cardiac Rehabilitation Programme. Demographic variables were collected (International Index of Erectile Function (IIEF), quality of sexual life (mSLQQ), anxiety and depression (HAD), along with cardiovascular risk factors (CVRF). Genetic analysis of polymorphisms T-786C, G894T of the eNOS gene was performed by RT-PCR with TaqMan probe, and the data were analysed using SPSS 25.
Patients (n = 35, 60.8 ± 8.44 years) showed a median CVD (IQR 1-3) with severe ED (IIEF-EF of 9.4 ± 6.73 points) and a low perception of their quality of sexual life (-19.4 ± 8.37 points). At the final visit (n = 15), there were 71% responders to treatment with iPDE5, with a significant improvement in their ED (IIEF = 49.4 ± 17.29, IIEF-FE = 18.5 ± 9.60 scores) and of their quality of sexual life (7 ± 12 scores), with a higher percentage of responders among the native homozygous genotypes -786-TT and 864-TT.
Variants of the NOS3 gene could influence the response to iPDE5. Full analysis of the patient sample will be required to confirm these preliminary results.

OBJECTIVE: To investigate whether endothelial nitric oxide synthase (eNOS) T786C, 4VNTR and G894 T gene polymorphisms could mediate in andrological treatment response in Spaniards.
UNASSIGNED: The study participants were Spaniard males with erectile dysfunction (ED) and chronic pain (n = 105) recruited at the Pain Unit. eNOS polymorphisms were genotyped by quantitative polymerase chain reaction using Taqman specific probes. Statistical analyses were carried out using R-3.2.4 software.
RESULTS: A total of 69 patients required andrological treatment and 76% of them improved ED upon iPED5 (20%), testosterone (35%) or iPDE5/testosterone treatment (45%); being significantly better in T786C-CC patients. Multivariate regression analysis indicated that age, opioid daily dose and carriage of T786C-C allele influenced the risk and ED severity in Spaniard chronic pain patients.
CONCLUSIONS: T786C polymorphism at eNOS locus appeared to be a major contributor in the variable erectile function iPDE5/testosterone response in Spaniards.

BACKGROUND: Several case-control studies have been performed to investigate the association between 894 G > T polymorphism in endothelial nitric oxide synthase (eNOS) gene and susceptibility to preeclampsia. However, the results were inconsistent and inconclusive. Therefore, we conducted this meta-analysis to investigate the association. Methods: All studies published up to September 30, 2019 were identified by searching electronic databases such as PubMed, EMBASE, CNKI, and WANFANG. Results: A total of 35 case- control studies with 4,254 cases and 5,801 controls were selected. There was a significant association between the eNOS 894 G > T and preeclampsia risk. When stratified by ethnicity, an increased risk of preeclampsia was found in Caucasian and Mixed populations, but not in Asians or Africans. Conclusion: Based on our meta-analysis, the eNOS 894 G > T polymorphism was associated with an increased risk of preeclampsia, especially among Caucasian and Mixed populations.

Effects of trimetazidine combined with berberine on endothelial function of patients with coronary heart disease combined with primary hypertension (CCP) were investigated. A total of 68 patients with CCP were selected from July 2014 to August 2016 to serve as observation group. At the same time, 68 healthy people were also selected to serve as control group (physiological saline). Expression of endothelial nitric oxide synthase (eNOS) mRNA in the blood samples of the observation and control groups before and after treatment was determined by RT-PCR. Levels of NO in the plasma of the observation and control groups before and after treatment were measured by nitric acid reductase method. Brachial artery flow-mediated vasodilation (FMD) of observation and control groups was detected by brachial artery ultrasonography before and after treatment. Before treatment, expression level of eNOS mRNA in blood of the observation group was significantly lower than that of the control group (P<0.05). After treatment, expression level of eNOS mRNA was significantly increased (P<0.05). Plasma NO content 41.06±3.63 mol/l in blood of the observation group was significantly lower than that of the control group 53.28±3.09 mol/l (P<0.05). After treatment with trimetazidine and berberine, level of NO 50.75±2.75 mol/l was significantly increased compared with the level before treatment (P<0.05). FMD value (5.03±0.95) was significantly lower in observation group than that in control group (16.04±1.63) (P<0.05). After treatment with trimetazidine and berberine, FMD value (14.02±2.39) was significantly increased compared with the level before treatment (P<0.05). The results suggested that the combination of trimetazidine and berberine can increase the content of NO in blood and promote endothelium-dependent dilation function of brachial arteries, which is helpful in the treatment of CCP.

This study aimed to investigate whether functional variants of endothelial nitric oxide synthase (eNOS) gene play any role in rheumatoid arthritis (RA) ethiopathogenesis and treatment in the Turkish population. Because, eNOS variants are responsible for alteration of the NO level in plasma, by reducing/increasing the endothelial NO synthesis. In the study, two eNOS gene variants (G894T and intron 4 VNTR A/B) were examined at extracted DNAs from 65 peripheral blood cell of RA patients. For the control, blood samples obtained from 70 healthy persons were studied. Genotyping of molecular variants was performed by PCR-RFLP and/or PCR technique. The data obtained was compared in itself and response to therapy. We found that \"TT genotypic frequency\" for the G894T variant was significantly associated with RA with an overall risk of 8.3-fold (p 0.029). No association was identified between intron 4 VNTR A/B variant and RA. At the 6 months, the mean visual analog scale (VAS), health assessment questionnaire (HAQ), and disease activity score for 28 joints (DAS 28) improvement was not significant among groups. Improvement in DAS was significantly better in anti-TNF treatment than disease-modifying antirheumatic drugs (DMARD) treatment treated subgroup. We report for the first time that variants in the eNOS \"TT\" genotype might be contributed to the increased risk of RA in the Turkish population. These results imply that functional variants of eNOS gene might have an effect on RA patients and response to anti-TNF treatment. In addition, the results suggest that eNOS variants might be associated and affect host susceptibility and/or response to treatment in Turkish RA patients.