A randomized, placebo-controlled, double blind, 4-period, cross-over trial, to study the effects of aliskiren, hydrochlorothiazide and moxonidine on endothelial dysfunction in obesity related hypertension

Patient is a male or post-menopausal female of 30-70 years of age on the day of signing informed consent. Post menopausal status is assumed if a woman has not experienced a menstrual bleed for a minimum of 12 months, assuming that she still has a uterus, and is not pregnant or lactating. In women without a uterus, menopause or postmenopause is defined by a very high FSH level. All patients should fulfil the diagnostic criterion of abdominal adiposity: waist circumference > 102 cm (men) or > 88cm (women). The waist circumference is measured halfway between the lower rib and iliac crest in standing position. All patients should fulfil the following diagnostic criterium for hypertension: - SBP >/= 130 mmHg and/or DBP >/= 85 mmHg during both visits. Blood pressure is assessed by office readings in accordance with current guidelines for hypertension diagnosis. The patient needs to be seated some minutes before and during the measurement. The cuff size should be adjusted to the patients* arm circumference and needs to be on the same height level as the patients* sternum during the measurements. Blood pressure is determined to a 2 mmHg accuracy-level. Blood pressure is measured on both arms during the first visit. In both measurements differ more than 10 mmHg, the highest value is taken. After at least 15 seconds, the measurement is repeated during the same visit. The highest mean of the two measurements on the same arm is considered as the actual blood pressure value. Patients should fulfil one or more of the following criteria to meet the definition of the metabolic syndrome: - Hypertriglyceridemia (serum triglycerides >/= 1.7 mmol/L); - Low High-density lipoprotein (HDL)-cholesterol (serum HDL-cholesterol < 1.04 mmol/L (men) or < 1.29 mmol/L (women)); - High fasting glucose (fasting serum glucose > 5.6 mmol/L). Patient understands the study procedures, alternative treatments available, and risks involved with the study and voluntarily agrees to participate by giving written informed consent.

SBP > 180 mmHg and/or DBP > 110 mmHg during one or more screening measurements and/or use of more than one type of antihypertensive medication. Ten year cardiovascular mortality risk according to the SCORE-risk model > 10% BMI > 35 kg/m2 Current smoking or smoking during the previous 3 months Use of *recreational* or illicit drugs Recent history (within the last year) of alcohol abuse or dependence. History of hypersensitivity reactions or intolerance to any (components of) medication used in this trial. Current / recent participation (within 30 days of signing informed consent) in a study with an investigational compound or device. Laboratory values as listed below: - Hemoglobin (Hb) < 8,6 mmol/L (men) or < 7.4 mmol/L (women) - TSH <0.3 mcIU/mL or > 5.0 mcIU/mL - Potassium < 3,8 mmol/L or > 5,0 mmol/L - Sodium < 136 mmol/L or > 146 mmol/L - MDRD < 60 mL/min/1,73m2 Medical conditions as listed below: - Secondary hypertension - Congestive Heart Failure - Atherosclerotic vascular disease. (As per NCEP ATP III and AHA/ACC Guidelines: Established atherosclerotic vascular disease includes history of myocardial infarction, stable angina, coronary artery procedures (angioplasty or bypass surgery) or evidence of clinically significant myocardial ischemia. Other atherosclerotic vascular disease includes clinical manifestations of non-coronary forms of atherosclerotic disease (peripheral arterial disease, cerebrovascular disease, abdominal aortic aneurysm, and carotid artery disease [transient ischemic attacks or stroke of carotid origin or >50% obstruction of a carotid artery]). - Cardiac arrhythmia*s, for example bradycardia, atrial fibrillation, sick-sinus syndrome, sinoatrial block, atriovertricular block or any other arrhythmia. - Obstructive sleep apnea syndrome (OSAS) or a score of 10 or higher on the Epworth Sleepiness Scale questionnaire. - Type 2 diabetes mellitus - Serious liver function disorders (Child-Pugh-Class C). - COPD (GOLD classification of severity 2 or higher) - Celiac disease or other significant intestinal malabsorption - Malignancy <= 5 years prior to signing informed consent, except for adequately treated basal or squamous cell skin cancer or in situ cervical cancer. - Mental instability or major psychiatric illness - Polyneuropathy or clinical suspicion for autonomic nervous system dysfunction. - Any diseases that would limit or complicate study evaluation or participation. - Any diseases or screening abnormalities that call for treatment that can not be postponed until after the study period without causing harm. Any concomitant medication, particularly antihypertensive co-medication, glucose lowering medication, lipid lowering drugs, systemic corticosteroids, birth control pills and vitamin C or E supplements, but also any other kinds of drugs, including over the counter medication. Exceptions can be made for the following categories of drugs: - paracetamol; - proton-pump inhibitors; - topical creams and unguents that do not lead to uptake of any of the active components into the circulation (in case of steroid creams: class II or lower); - inhalation medication, nasal sprays and eye drops that do not lead to uptake of any of the active components into the circulation.