This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The angiotensin II-infused rat is a model for angiotensin II-dependent hypertension, in these rats both kidneys are exposed to elevated levels of angiotensin II and elevated perfusion pressure. Previous studies have shown that heme oxygenase (HO), an enzyme that catalyzes the conversion of heme to biliverdin, free iron and carbon monoxide (CO), is upregulated in kidneys from angiotensin II-infused rats indicating a possible protective role of heme oxygenase in angiotensin II-mediated hypertension. We hypothesize that heme oxygenase is upregulated in kidneys of angiotensin II-dependent hypertensive rats, and that HO-derived metabolites (CO and/or bilirubin) regulate renal hemodynamics by counteracting the effects of elevated angiotensin II levels and dilating the renal afferent and efferent arterioles, thus improving renal function.
The aims of this study are: 1) To determine the effect of chronic angiotensin II infusion on renal arteriolar and tubular HO expression using immunohistochemical and western blot analyses. 2) To determine the effect of HO induction or inhibition on afferent and efferent arteriolar vasoactivity and responsiveness to angiotensin II, and on afferent arteriolar autoregulatory responses in normotensive and angiotensin II-hypertensive rats. Afferent and efferent arteriolar responses will be evaluated using the blood-perfused juxtamedullary nephron preparation. 3) To determine the effect of acute HO inhibition on renal hemodynamics, autoregulation, and pressure-natriuresis in angiotensin II-infused rats, using in vivo renal clearance studies.

National Institute of Health (NIH)
National Center for Research Resources (NCRR)
Exploratory Grants (P20)
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Special Emphasis Panel (ZRR1-RI-5 (01))
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Tulane University
Schools of Medicine
New Orleans
United States
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