Effects of Sildenafil in Resistant Hypertensives and Genetic Polymorphism
Condition: Hypertension
MeSH terms: Hypertension
Study type: Interventional

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.
    

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.
    

Intervention name(s): sugar pill; sildenafil
Intervention type(s): Other; Drug
Intervention description(s): Sugar pills: 37.5, 50.0, and 100.0 mg each 30 minutes.; Sildenafil pills: 37.5, 50.0, and 100.0 mg each 30 minutes.
Other intervention name(s): No brand name.; Viagra, Pfizzer Lab., USA
Intervention MeSH terms: Sildenafil Citrate
Allocation: Non-Randomized
Intervention model: Crossover Assignment
Masking: Single (Participant)
Primary purpose: Treatment
Keywords: Sildenafil; Nitric oxide synthase; Polymorphism; Hemodynamics