Hypertension
Conditions
Keywords
Tadalafil, Resistant Hypertension, Left Ventricle Diastolic Dysfunction, Brain natriuretic peptide
Brief summary
Left ventricle diastolic dysfunction (LVDD) is associated with resistant hypertension. In addition, brain natriuretic peptide (BNP) levels are elevated when LVDD is present. It has been shown that phosphodiesterase-5 (PDE5) inhibition improves left ventricle diastolic function in hypertensive rats, despite any difference in blood pressure levels. Also, left ventricle diastolic function enhancement reduces BNP concentration in hypertensive patients. However, it is unknown if these effects exists in humans with resistant hypertension. Therefore, this study was developed to evaluate if the use of a PDE5 inhibitor (tadalafil) for 2 weeks improves LVDD and its effects in BNP levels in resistant hypertensive patients.
Detailed description
Resistant hypertensive patients have a high incidence of left ventricle diastolic dysfunction (LVDD). Lowering blood pressure levels improves diastolic function, however, there is no proved effective treatment specifically for this disease. Studies in hypertensive rats have shown presence of phosphodiesterase-5 in cardiac cells and an improvement in left ventricle diastolic function using a phosphodiesterase-5 (PDE5) inhibitor, the sildenafil. PDE5 has also been demonstrated in human heart cells with cardiac disease. In addition, LVDD is associated with high levels of brain natriuretic peptide (BNP), which reduces with diastolic function improvement. Therefore, it is reasonable to suppose that PDE-5 inhibitor use in humans with LVDD and resistant hypertension could improve diastolic function. Objective: Evaluate the chronic effect of a PDE-5 inhibitor on LVDD and BNP levels in resistant hypertensive patients. Casuistic and methods: 20 resistant hypertensive patients with LVDD types I and II will be evaluated with echocardiography study, ambulatory blood pressure monitoring (ABPM), office blood pressure measurements, endothelial function analysis using the brachial artery flow mediation dilation technique (FMD) and BNP plasma levels. Then, the subjects will receive oral placebo for 2 weeks. After this period, the same exams will be repeated. Two weeks later, the protocol will be performed again to the same 20 patients, using tadalafil (the longest half-life PDE-5 inhibitor) 20mg orally instead of the placebo. Hypothesis: investigators hypothesize that the use of tadalafil will improve left ventricle diastolic function with BNP reduced levels and this effect will be independent of blood pressure decrease or endothelial function improvement.
Interventions
OTHERsugar pill
Sugar pills: 20mg orally, once a day for 2 weeks
DRUGTadalafil
Tadalafil pills: 20mg orally, once a day for 2 weeks.
Sponsors
Fundação de Amparo à Pesquisa do Estado de São Paulo
University of Campinas, Brazil
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
35 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* resistant hypertension (according to Resistant Hypertension - American Heart Association Statement - 2008); * compliance with antihypertensive treatment; * age \>35 years; * left ventricle diastolic dysfunction types I and II
Exclusion criteria
* valvulopathy * decompensated heart failure * important cardiac arrhythmias * nephropathy * hepatopathy * autoimmune disease * tabagism * decompensated diabetes * uncontrolled dislipidemia
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Left Ventricle Diastolic Dysfunction | Baseline and 2 weeks | Outcome measurement assessed by Echocardiogram before and after a 2-week tadalafil administration period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in endothelial function | baseline and 2 weeks | Outcome measure assessed by flow-mediated dilation before and after a 2-week tadalafil administration period. |
| Change in blood pressure levels | Baseline and 2 weeks | Blood pressure measurements assessed before and after a 2-week tadalafil administration period. |
| Change in B-type Natriuretic Peptide (BNP-32) levels | Baseline and 2 weeks | Plasma brain natriuretic peptide (BNP-32)assessed before and after a 2-week tadalafil administration period |
| Change in cyclic guanosine monophosphate (cGMP) levels | Baseline and 2 weeks | Cyclic guanosine monophosphate (cGMP) levels assessed before and after a 2-week tadalafil administration period |
| Change in nitrite levels | Baseline and 2 weeks | Nitrite levels assessed before and after a 2-week tadalafil administration period. |
Countries
Brazil
Outcome results
None listed