Raij Laboratory

General Information

Leopoldo Raij, MD
Professor, Medicine / Nephrology

Research Interests

• Mechanisms of Vascular and Renal Injury in Hypertension, interaction between the Renin- Angiotensin System and Nitric Oxide
• Mechanisms of Vascular and Renal Injury in Salt-Sensitive Hypertension
• Mechanisms of Vascular Insulin Resistance in Hypertension and Aging
• Cardiovascular Risk Factors and the Endothelium
• Oxidative Stress in Cardiovascular and Renal Injury
• Pathophysiology of Diabetic Renal disease
• Role of Cigarette Smoke and Nicotine in Vascular Disease

Keywords and Phrases

• Salt-sensitive hypertension
• Vascular insulin resistance in aging and hypertension
• Aging-induced renal injury
• Hypertensive renal injury
• Endothelial dysfunction
• Nitric oxide
• Renin-angiotensin system
• Oxidative stress

Contact Information

• Office location: Veterans Affairs Medical Center
  1201 NW 16^th Street, Room A1009
  Miami, FL 33125
• Tel: (305) 575-3103
• Fax: (305) 575-3378
• Lab Location: Veterans Affairs Medical Center
  1201 NW 16^th Street
  Miami, FL 33125
• E-mail: LRaij@med.miami.edu

Members

Research

Salt-sensitive hypertension
Salt sensitivity, an independent risk factor for increased cardiovascular and renal morbidity and mortality, affects approximately 50% of hypertensives. Studies from our laboratory have demonstrated that salt-sensitive hypertension is a vascular diathesis characterized by a local activation of angiotensin II and NAD(P)H oxidase-derived reactive oxygen species in the setting of insufficient nitric oxide. In hypertensive Dahl salt-sensitive rats, a paradigm of human salt-sensitive hypertension characterized by cardiovascular and renal injury, inhibition of angiotensin II type 1 receptor or NAD(P)H oxidase-derived reactive oxygen species prevents the development of endothelial dysfunction, upregulation of proatherogenic molecules, and vascular reactive oxygen species generation, independently of blood pressure.  To the extent that vascular disease is characterized by an imbalance among nitric oxide, angiotensin II, and reactive oxygen species in the endothelium, modulating the activity of these vasoactive substances has important implications for the treatment of hypertension and the prevention of atherosclerosis and end-organ damage. Our studies focus on developing therapeutic strategies in hypertension that focus on preserving endothelial integrity and on preventing the development of endothelial dysfunction, vascular inflammation, and atherosclerosis by restoring the balance between counteracting vasoactive factors.

Vascular Insulin Resistance
Insulin resistance, endothelial dysfunction, and hypertension (HTN), central features of the metabolic syndrome, are more prevalent among the aging population. Angiotensin (Ang) II, oxidative stress, and inflammation play a causal role in numerous settings of insulin resistance, including obesity, type 2 diabetes, and salt-sensitive hypertension. However, the mechanisms underlying the development of insulin resistance with aging are less well understood. Our recent studies suggest that vascular insulin resistance in aging may contribute to the development of hypertension and may be an early phenomenon that precedes the development of metabolic insulin resistance, systemic oxidative stress, and endothelial dysfunction. Furthermore, impaired vascular relaxation to insulin in aging may add to the increased susceptibility of this population to vascular injury induced by cardiovascular risk factors, such as obesity, diabetes, hypertension, smoking, and dyslipidemia.

Selected Publications

• Zhou M-S, Schulman IH, Jaimes EA, Raij L. Renoprotection by Statins is Linked to a Decrease in Renal Oxidative Stress, TGFb, and Fibronectin with Concomitant Increase in Nitric Oxide Bioavailability. American Journal of Physiology: Renal Physiology, 2008 (in press)
• Zhou M-S, Schulman IH, Jaimes EA, Raij L. Thiazide Diuretics, Endothelial Function, and Vascular Oxidative Stress. Journal of Hypertension, 26: 494-500, 2008
• Schulman IH, Zhou M-S, Jaimes EA, Raij L. Dissociation between Metabolic and Vascular Insulin Resistance in Aging. American Journal of Physiology: Heart and Circulatory Physiology, 293: H853-H859, 2007
• Zhou M-S, Schulman IH, Pagano PJ, Jaimes EA, Raij L. NAD(P)H Oxidase in Low Renin Hypertension: Link among Ang II, Atherogenesis and Blood Pressure. Hypertension, 47: 81-86, 2006
• Zhou MS, Jaimes EA, Raij L. Differential Role of Oxidative Stress and Calcineurin in Angiotensin II-induced Cardiovascular Remodeling? Journal of Hypertension; 23: 1737-1743, 2005
• Schulman IH, Raij L. Salt sensitivity and Hypertension after Menopause: Role of Nitric Oxide and Angiotensin II. American Journal of Nephrology, 26: 170-180, 2006
• Schulman IH, Zhou M-S, Raij L. Nitric Oxide, Angiotensin II, and Reactive Oxygen Species in Hypertension and Atherogenesis. Current Hypertension Reports, 7: 61-67, 2005
• Harrison-Bernard LM, Schulman IH, Raij L. Post Ovariectomy Hypertension is Linked to Increased Renal AT1 Receptor and Salt-Sensitivity. Hypertension, 42: 1157-1163, 2004
• Zhou MS, Jaimes EA, Raij L: Statins prevent end-organ injury in salt-sensitive hypertension: role of eNOS and oxidant stress. Hypertension 2004; 44:186-190
• Zhou MS, Jaimers EA, Raij L: Inhibition of superoxide generation and improvement of endothelial function by amlodipine in angiotensin II-infused rats. American Journal of Hypertension. 2004; 17(2): 2004; 17(2):167-171
• Zhou MS, Adam A, Jaimes EA, Raij L: In salt-sensitive hypertension, increased superoxide production is linked to functional upregulation of angiotensin II. Hypertension. 2003; 42:945-951 production is linked to functional upregulation of angiotensin II. Hypertension. 2003; 42:945-951