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Completed

NCT Number: NCT01392638

Effects of Sildenafil in Resistant Hypertensives and Genetic Polymorphism

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.

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Key information

Conditions

Hypertension Cardiovascular Diseases Vascular Diseases

Age range

35 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Laboratory of Cardiovascular Pharmacology - FCM - Unicamp

Campinas, São Paulo, Brazil

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Sugar Pill

Other

Sugar pills: 37.5, 50.0, and 100.0 mg each 30 minutes.

Other names: No brand name.

Sildenafil

Drug

Sildenafil pills: 37.5, 50.0, and 100.0 mg each 30 minutes.

Other names: Viagra, Pfizzer Lab., USA

Primary outcomes

  1. Cardiac Output, total peripheral resistance, mean arterial pressure

    Time frame: Each 30 minutes

    Hemodynamic measures each 30 minutes

Secondary outcomes

  1. Left ventricular diastolic function parameters, endothelial function

    Time frame: Pre- and post-sildenafil accumulated doses

    Assessment of how hemodynamic changes determined by sildenafil would affect endothelial and left ventricular diastolic parameters.

Sponsors and collaborators

Lead sponsor

University of Campinas, Brazil

Other

Collaborators

  • Fundação de Amparo à Pesquisa do Estado de São Paulo

Registry information

Official study title

Influence of the Nitric Oxide Synthase T-786C Polymorphism on the Response to Acute Inhibition of Phosphodiesterase 5 in Resistant Hypertension

Important dates

Study start
2010
Primary completion
2012
Study completion
2012
First posted
Jul 12, 2011
Registry last updated
Oct 30, 2012

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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