Effects of phosphodiesterase 5 inhibition on cardiovascular function in resistant hypertension: A systematic review.

Approximately 12-18% of hypertensive patients are diagnosed with resistant hypertension (RH). The risk of having worse cardiovascular outcomes is twice higher in those patients. The low effectiveness of conventional antihypertensive drugs in RH emphasizes the need to evaluate complementary drug therapies to achieve blood pressure (BP) control. Previous studies have demonstrated that phosphodiesterase 5 (PDE-5) inhibitors improve hemodynamics and reduce BP on essential hypertension. So, the authors aimed to summarize current clinical trials-based evidence published concerning the use of PDE-5 inhibitors on BP, cardiovascular function, and hemodynamics of patients with RH. We searched MEDLINE, EMBASE, LILACS, ClinicalTrials.gov, and WHO International Clinical Trials Registry databases on May 15th, 2020 using pre-defined search terms. Two independent reviewers assessed and extracted data from clinical trials that evaluated the effect of PDE-5 inhibitors on BP. We have included five articles in this systematic review. Four of them developed a single-day protocol, while one has developed a 14-day study. The main findings indicate that PDE-5 inhibitors ameliorate BP, vascular hemodynamics, and diastolic function parameters. Some data demonstrated improvement of endothelial function, but it was not a consensus. The side effects seemed to be limited and well-tolerated. In brief, our systematic review highlights the potential of PDE-5 inhibitors as a therapeutic alternative in addition to the multiple-drug regime for RH. Larger studies are still needed to determine whether the beneficial effects of PDE-5 inhibitors on RH would be maintained with chronic administration.

Oscillatory shear stress induces hemostatic imbalance in healthy men.

INTRODUCTION: In vitro and animal model studies have demonstrated that oscillatory shear can trigger vascular hemostasis and remodeling. However, the roles of hemodynamic forces in vascular human biology are not well understood. This study aimed to determine the effects of increasing oscillatory shear stress (OSS) on coagulation/fibrinolysis factors and matrix metalloproteinase-9 activity in healthy subjects. MATERIALS AND METHODS: Ten healthy males (35 ±â€¯7 years) underwent a 30-minute dominant forearm cuff occlusion (75 mm Hg) to exacerbate OSS in the brachial artery. Blood flow was quantified (Doppler ultrasound), and plasma samples were obtained from both arms at rest and during the last 30 s of cuff occlusion on the dominant arm. A proximal cuff (40 mm Hg, close to axilla) was also occluded to facilitate venous blood biomarker trapping. RESULTS: The retrograde shear rate and oscillatory shear index were increased and the mean shear rate, mean blood velocity, and mean blood flow were decreased in the cuffed arm (p < 0.05 vs. baseline and non-cuffed arm). Cuff occlusion induced increases in platelet microparticle release (p = 0.05 vs. baseline), prothrombin time (p < 0.05 vs. baseline and non-cuffed arm), tissue plasminogen activator (p < 0.01 vs. baseline and non-cuffed arm), plasminogen activator inhibitor-1 (p < 0.02 vs. baseline and non-cuffed arm), and matrix metalloproteinase-9 activity (p = 0.01 vs. baseline). No significant changes were found in the non-cuffed arm throughout the protocol. CONCLUSIONS: Exacerbation of OSS induced in vivo disturbances in platelet microparticle release, coagulation-fibrinolysis, and matrix metalloproteinase-9 activity in healthy individuals. These are potential mechanisms involved in OSS-mediated endothelial dysfunction.

Metabolic syndrome components and estimated glomerular filtration rate based on creatinine and/or cystatin C in young adults: A gender issue?

AIMS: This work aims to identify correlations between estimated glomerular filtration rate (eGFR) based on creatinine and/or cystatin C (Cr, CysC) with metabolic syndrome (MS) components in young adults, according to gender. MATERIAL AND METHODS: This is a cross sectional study, where young adults aged between 18 and 30 were matched by gender, age and body mass index. All subjects underwent clinical evaluation and blood sampling for laboratory measurements. MS was determined according to the JIS criteria. The eGFR was estimated using CKD-EPI equations (eGFRCr; eGFRCysC; eGFRCr-CysC). RESULTS: We evaluated 78 subjects with a mean age of 24.5 years. 10.2% had MS, with higher incidence among males (15.4% ♂ vs. 5.1% ♀). Elevated waist circumference was the MS component most observed. Significant correlations (Pearson; p<0.05) between eGFR and metabolic markers were observed only in males. In addition, we observed a significant association between the increase of MS components and the decay of eGFRCr and eGFRCr-CysC (zero vs. two or more components, ANOVA, p<0.05) only among males. CONCLUSION: eGFR decay associated with components of MS and insulin resistance in young male adults could represent a worrying specific risk and indicate that further studies are needed to better understand these findings.