Effects of Sildenafil in Resistant Hypertensives and Genetic Polymorphism
Information source: University of Campinas, Brazil
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Hypertension
Intervention: sugar pill (Other); sildenafil (Drug)
Phase: N/A
Status: Completed
Sponsored by: University of Campinas, Brazil Official(s) and/or principal investigator(s): Heitor Moreno, PhD, Principal Investigator, Affiliation: Faculty of Medical Sciences - Unicamp
Summary
Sildenafil citrate slightly reduces blood pressure in treated hypertensives patients.
However, it is unknown if the simultaneous use of sildenafil plus, at least, 3 classes of
antihypertensive agents in patients with resistant arterial hypertension may have a synergic
effect on the patients blood pressure. Moreover, sildenafil improves the endogen nitric
oxide effects. The nitric oxide is an important signaling molecule in the body that
contributes to vessel homeostasis by inhibiting vascular smooth muscle contraction and
growth. Hypertension often impaired NO pathways. Nitric oxide is produced by an enzyme,
called nitric oxide synthase (NOS3), that show some genetics variants, which means that this
enzyme can be different from person to person. Therefore, the objective of the present study
is to examine the influence of a genetic variant (known to affect NOS3 levels) in sildenafil
acute effects on hemodynamic and cardiovascular function. The investigators hypothesis is
that individuals with the genetic variant associated to higher levels of NOS3 will have more
benefits from sildenafil treatment.
Clinical Details
Official title: Influence of the Nitric Oxide Synthase T-786C Polymorphism on the Response to Acute Inhibition of Phosphodiesterase 5 in Resistant Hypertension
Study design: Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment
Primary outcome: Cardiac Output, total peripheral resistance, mean arterial pressure
Secondary outcome: Left ventricular diastolic function parameters, endothelial function
Detailed description:
Endothelial dysfunction is one of the mechanisms involved in the maintenance of the high
blood pressure levels in resistants hypertensives patients, which is directly related to the
NO-GMPc pathway. The phosphodiesterase 5 inhibitor, sildenafil citrate, slightly reduces
systolic and diastolic blood pressures in treated hypertensives patients. However, it is
unknown if the simultaneous use of sildenafil plus, at least, 3 classes of antihypertensive
agents in patients with resistant arterial hypertension may have a synergic effect on the
patients blood pressure. Moreover, sildenafil improves the endogen nitric oxide effects
produced by eNOS. Therefore, since the genetics polymorphisms of eNOS can affect the NO
tissue levels, it seems reasonable to suppose that the acute effects of sildenafil may be
modulated by them. Objective: To examine the influence of the T-786C polymorphism of eNOS
gene in sildenafil acute effects on hemodynamic and cardiovascular function in resistant
hypertensives patients. Casuistics and Methods: Around 120 patients with HAR will be
genotyped for the T-786C eNOS polymorphism, from which the investigators will enroll in this
study 15 patients with TT genotype and 15 patients with CC genotype. The patients will be
monitored with the Portapres system (non-invasive hemodynamic). After basal records of the
studied variables, increasing doses of sildenafil will be administrated (37. 5, 50. 0 e 100. 0
mg). Five minutes before each new dose, the studied variables will be recorded again.
Hypothesis: The investigators hypothesize that the sildenafil, besides the anti-ischemic
effect, will improve the patients hemodynamic status and, moreover, that it will occur a
modulation of this effect by the T-786C polymorphism.
Eligibility
Minimum age: 35 Years.
Maximum age: 75 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- resistant hypertensive (according to Resistant Hypertension - AHA Statement - 2008);
- compliance with antihypertensive treatment;
- age >35 years;
- diastolic dysfunction
Exclusion Criteria:
- valvulopathy
- decompensated heart failure
- important cardiac arrhythmias
- nephropathy
- hepatopathy
- autoimmune disease
- tabagism
- decompensated diabetes
- uncontrolled dislipidemia
Locations and Contacts
Laboratory of Cardiovascular Pharmacology - FCM - Unicamp, Campinas, SP, Brazil
Additional Information
Starting date: July 2010
Last updated: October 29, 2012
|