Racial Variation in ACE--Genetic and Physiologic Bases
Summary
To determine whether differences in the activity of the renin-angiotensin and bradykinin systems are involved in the pathogenesis of blood pressure variation in African Americans.
Description
BACKGROUND:
Each year, more than 40,000 new patients require treatment for end stage renal disease, a condition which is 4-fold higher among African Americans than Caucasians. Trials of angiotensin converting enzyme inhibitors (ACEIs) in Caucasians support a role of the renin-angiotensin system in the pathogenesis of glomerulosclerosis. Yet, despite the high prevalence of nephropathy among African Americans, Blacks have been under-represented in studies in ACEIs. Data from our laboratory suggest that the renal effects of ACEI may differ in African Americans. African Americans are resistant to the anti-hypertensive effects of ACEI and, thus, may be resistant to the renoprotective effects as well. The ACE deletion allele, a variant associated with increased ACE activity and progression of renal diseases, is increased in frequency in African Americans, while the frequency of the Ang AT1 receptor C allele, a variant associated with antihypertensive responsiveness to ACEI is decreased. Moreover, African Americans exhibit decreased sensitivity to Ang I and increased sensitivity to bradykinin. Taken together, these data suggest the hypothesis that ACE activity is increased in African Americans, leading to decreased bradykinin levels ( and receptor sensitization) and increased tissue Ang II (and receptor desensitization).
DESIGN NARRATIVE:
The study tests the hypothesis that ACE activity is increased in African Americans, leading to decreased bradykinin levels (and receptor sensitization) and increased tissue Ang II (and receptor desensitization). The effects of race, hypertension and ACE insertion/deletion genotype on ACE activity will be determined, as measured by the pressor and renal vasoconstrictor responses to Ang I and Ang II and the vasodilator response to bradykinin. Specific bradykinin and angiotensin receptor antagonists will be used to determine the relative contribution of increased bradykinin and decreased angiotensin II to the renal hemodynamic effects of ACEIs in African Americans and Caucasians.
Study Design
Observational Model: Defined Population
Conditions
Cardiovascular Diseases
Status
Completed
Source
National Heart, Lung, and Blood Institute (NHLBI)
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00005757
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Cardiovascular Diseases
Pathological conditions involving the CARDIOVASCULAR SYSTEM including the HEART; the BLOOD VESSELS; or the PERICARDIUM.
Diagnostic Techniques, Cardiovascular
Methods and procedures for the diagnosis of diseases or dysfunction of the cardiovascular system or its organs or demonstration of their physiological processes.
Death, Sudden, Cardiac
Unexpected rapid natural death due to cardiovascular collapse within one hour of initial symptoms. It is usually caused by the worsening of existing heart diseases. The sudden onset of symptoms, such as CHEST PAIN and CARDIAC ARRHYTHMIAS, particularly VENTRICULAR TACHYCARDIA, can lead to the loss of consciousness and cardiac arrest followed by biological death. (from Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine, 7th ed., 2005)
Cardiovascular Physiological Phenomena
Processes and properties of the CARDIOVASCULAR SYSTEM as a whole or of any of its parts.
Dental Care For Chronically Ill
Dental care for patients with chronic diseases. These diseases include chronic cardiovascular, endocrinologic, hematologic, immunologic, neoplastic, and renal diseases. The concept does not include dental care for the mentally or physically disabled which is DENTAL CARE FOR DISABLED.
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