Vascular Dysfunction in Human Obesity Hypertension

The purpose of the study is to test the effects of: 1) blocking sympathetic nerve activity with a drug called clonidine, and 2) by blocking a kidney protein called renin, and on blood vessel function and muscle nerve activity in adults who are obese and have high blood pressure. Years 1 and 2: The 1st cohort of subjects will consist of 69 healthy young men and women age 18-79 years who are obese, defined as a body mass index > or = to 30 kg/m2, who have untreated systolic hypertension (systolic blood pressure > or = to 130 - <180 mmHg- average of at least 3 measurements 2 min apart after 10 min seated resting position). These 69 subjects will then be randomized to 3 treatment arms: clonidine (0.1 mg/day), hydrochlorothiazide (25 mg/day) or placebo for 4 weeks in years 1 and 2. All tablets will be encapsulated by to look identical. Subjects will randomly (1:1:1) receive one of the following combinations in a double-blind, placebo-controlled design: 1. Oral clonidine (0.1 mg twice/day) 2. Oral hydrochlorothiazide (12.5 mg twice/day) 3. Oral placebo In addition to 69 healthy young men and women, we will also enroll 15 obese adults with 'normal/optimal' systolic blood pressure (<120mmHg) who will undergo baseline testing only (Visits 1, 2 and 3). Years 3 and 4: A 2nd cohort of subjects (n=42) will be randomized to aliskiren (150 mg/day), hydrochlorothiazide (25 mg/day) or placebo for 4 weeks. All tablets will be encapsulated to look identical. Subjects will receive one of the following in a randomized, double-blind, placebo-controlled design: 1. Oral Aliskiren(150 mg/day- once per day) 2. Oral Hydrochlorothiazide (12.5 mg twice/day) 3. Oral placebo