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Purpose: Vascular endothelial growth factor (VEGF) is a potent angiogenic factor that affects blood pressure by promoting vasodilation mediated by nitric oxide. Angiotensin-converting enzyme inhibitors (ACEi) up-regulate the VEGF expression; thus, genetic polymorphisms in the VEGFA gene could affect the antihypertensive responses to these drugs. Methods: Hypertensive patients ( n = 102) were prospectively treated only with the ACEi enalapril for 60 days. We compared the effect of VEGFA polymorphisms on changes in blood pressure after enalapril treatment. In addition, multiple linear regression analysis was carried out to assess the effect of covariates on blood pressure. Genotypes for g.-2578C>A (rs699947), g.-1154G>A (rs1570360), and g.-634G>C (rs2010963) VEGFA polymorphisms were determined, and haplotype frequencies were estimated. Results: Individuals carrying the CA and AA genotypes for the g.-2578C>A polymorphism and the AGG haplotype showed more intense decrease in blood pressure in response to enalapril 20 mg/day. A multiple linear regression analysis showed that the AA genotype for the g.-2578C>A polymorphism and the AGG haplotype are associated with more intense decrease in blood pressure in response to enalapril 20 mg/day, while the CC genotype for the g.-2578C>A polymorphism and the CGG haplotype are associated with the opposite effect. Conclusions: These findings suggest that polymorphisms in VEGFA gene may affect the antihypertensive responses to enalapril. [ABSTRACT FROM AUTHOR]

Purpose: The antihypertensive effect of angiotensin-converting enzyme inhibitors (ACEi) is attributed partially to increased nitric oxide bioavailability. It is possible that functional polymorphisms in endothelial nitric oxide synthase ( eNOS) and bradykinin receptor B2 ( BDKRB2) genes may affect the antihypertensive response to enalapril. Methods: We evaluated 106 hypertensive patients treated only with enalapril for 60 days. The difference between the mean arterial pressure (MAP) before and after the antihypertensive treatment was defined as ΔMAP. If ΔMAP were below or above the median value, the patients were classified as poor responders (PR) or good responders (GR), respectively. eNOS genotypes for the TC, G894T and 4b/4a polymorphisms were determined and haplotype frequencies were estimated by PHASE and Haplo.stats programs. The CT and BE1 +9/-9 polymorphisms of BDKRB2 genes and their haplotypes were determined by DNA sequencing. Robust multifactor dimensionality reduction analysis was used to characterize gene-gene interactions. Results: The TC/CC genotypes and the C allele for the eNOS TC polymorphism were more frequent in GR than in PR. Furthermore, the TT genotype for the BDKRB2 CT polymorphism was more frequent in PR than GR. No other significant differences in genotypes or haplotypes were found. However, we found significant gene-gene interactions: the CC genotype for the BDKRB2 CT polymorphism was associated with response to enalapril depending on eNOS TC genotypes. Conclusions: These findings suggest that eNOS TC and BDKRB2 CT polymorphisms may synergically affect the antihypertensive response to enalapril. [ABSTRACT FROM AUTHOR]

Purpose: The antihypertensive effects of angiotensin-converting enzyme inhibitors (ACEi) are explained, at least in part, by enhanced bradykinin-dependent nitric oxide (NO) formation and decreased angiotensin II-induced oxidative stress and vasoconstriction. We examined for the first time whether treatment with enalapril increases the plasma levels of markers of NO formation and decreases oxidative stress in mild to moderate hypertensive patients. Methods: Eighteen untreated hypertensive patients were treated with enalapril 10 mg/day ( n = 10) or 20 mg/day ( n = 8) for 60 days. Eighteen normotensive healthy controls were followed for the same period. Venous blood samples were collected at baseline and after 30/60 days of treatment with enalapril. Plasma NOx (nitrites + nitrates) concentrations were determined by using the Griess reaction. Plasma nitrite and whole blood nitrite concentrations were determined by using an ozone-based chemiluminescence assay. Plasma thiobarbituric acid-reactive species (TBARS) and 8-isoprostane concentrations were determined by a fluorimetric method and by ELISA, respectively. Results: Treatment with enalapril decreased blood pressure in hypertensive patients. However, we found no significant changes in plasma NOx, nitrite, whole blood nitrite, and in the levels of markers of oxidative stress in both normotensive controls and hypertensive patients treated with enalapril. Conclusions: Our data show that enalapril 10-20 mg/day does not affect the concentrations of relevant markers of NO formation or markers of oxidative stress in mild to moderately hypertensive subjects, despite satisfactory blood pressure control. Our findings do not rule out the possibility that ACEi may produce such effects in more severely hypertensive patients treated with higher doses of ACEi. [ABSTRACT FROM AUTHOR]

In Brazil, the fruit of a native species that is popularly known as "jabuticaba" (Plinia cauliflora [Mart.] Kausel) is widely consumed fresh or used for the production of liqueur, juice, and jelly. In Brazilian folk medicine, this species is used to treat asthma, throat inflammation, and gastrointestinal and cardiovascular disturbances. However, no previous studies have reported its cardioprotective effects. To evaluate the possible cardioprotective effects of a hydroethanolic extract of Plinia cauliflora (EEPC) in female rabbits in a model of doxorubicin-induced heart failure. EEPC was obtained and fractionated by solid phase extraction, and its constituents were determined by liquid chromatography coupled to diode array detector and mass spectrometry (LC-DAD-MS). Thirty female New Zealand rabbits received doxorubicin administration for 6 weeks to induce heart failure. EEPC was orally administered at doses of 75 and 150 mg/kg daily for 42 days. Enalapril (5 mg/kg) was used as a reference cardioprotective drug. At the end of the experimental period, blood pressure and heart rate were recorded. Serum parameters, including lipid profile, troponin, creatinine, nitrotyrosine, malondialdehyde, nitrite, and brain natriuretic peptide, were measured. The electrocardiographic profile and renal vascular reactivity were evaluated. Cardiac histopathology and ventricular morphometry were performed, and the tissue enzymatic antioxidant system was investigated. A total of 37 compounds were detected in EEPC, including organic acids, phenolic acid derivatives, flavonoids, anthocyanins, and hydrolysable tannins (gallotannins and ellagitannins). EEPC treatment induced a cardiorenal protective response, prevented hemodynamic and functional alterations, and prevented ventricle remodeling. These effects were associated with the normalization of creatinine and brain natriuretic peptide levels and modulation of the tecidual antioxidant defense system. The present study demonstrated that EEPC may prevent doxorubicin-induced heart failure by modulating the antioxidant defense system, reducing reactive oxygen species-induced damage, preventing alterations of hemodynamic and endothelial function, and preventing damage to the cardiac structure. EEPC, especially at the highest dose tested, may be considered a cardioprotective coadjuvant to prevent doxorubicin-induced cardiotoxicity. Image 1 [ABSTRACT FROM AUTHOR]