RESEARCH PROJECTS

The role of 20-HETE in nitric oxide-mediated regulation of renal function
The primary objective of this proposal is to test the hypothesis that nitric oxide (NO) is involved in the transcriptional regulation of cytochrome (CYP)4A gene expression by peroxisome proliferator activated receptors alpha (PPAR ) and that this interaction defines the control of renal function and regulation of blood pressure. We propose that NO or peroxynitrite inhibits CYP4A gene and -hydroxylase and that removal of the tonic inhibitory influence of NO or induction of PPAR eventuates in increased CYP4A gene expression and 20-HETE production. We further propose that PPAR /NO interactions influence renal function in the ischemia-reperfusion model of acute renal failure. The following Specific Aims are proposed to test our hypothesis:
1. To demonstrate PPAR /nitric oxide interactions and evaluate the mechanisms involved.
2. To evaluate the physiologic correlates of the interactions of nitric oxide and PPAR -related, CYP4A-mediated responses in the kidney, and
3. To evaluate a role for nitric oxide in PPAR -mediated preservation of renal function in renal failure 

Interactions of nitric oxide and P450 epoxygenase arachidonate metabolites in the regulation of blood pressure
The primary objective of this proposal is to test the hypothesis that interaction of nitric oxide (NO) with epoxygenase metabolites of arachidonic acid (AA) are key components in the  homeostatic mechanism for the control of renal vascular tone and regulation of blood pressure.  The Specific aims are proposed to test the hypothesis are to:
1. Determine the effect of NO on CYP450-dependent epoxygenase AA metabolism and elucidate the mechanisms involved;
2. Determine the importance of epoxides and their role in cGMP-dependent and cGMP-independent effects of NO in the kidney vasculature; and,
3. Establish the physiological correlates of the interactions of NO with epoxygenases in endotoxic shock and acute renal failure 

HBCU Research Scientist Award
The major goal of this project is to enhance the biomedical research capability of Texas Southern University by developing a program of research excellence in cardiovascular diseases. Specific Aims are to:
1 Provide support for investigators to obtain independent research grants
2 Provide intensive laboratory training to students and increase the quality of biomedical graduate education, and
3 Strengthen science faculty and enhance biomedical research capability and capacity of TSU 

Transcriptional Regulation of renal function and blood pressure
Specific Aims
1 (a) To characterize vascular and renal function in mice lacking PPARα gene                                                                                                (b) To demonstrate PPARα/NO interactions in the kidney and identify the mechanisms involved             
2  To evaluate the physiologic correlates of the interactions of nitric oxide and PPAR -related responses in the kidney            
3 To evaluate the role of PPARα in DOCA/salt hypertension and evaluate the mechanisms involved               

Regulation of Cerebral microvascular endothelin production
Specific aims:
1. Characterize the effects of by-products of hemolyzed blood clots on ET-1 production.
2. Determine the cellular mechanism(s) by which spasmogenic agents released from
       blood clots stimulate ET-1 production. 

Mechanisms of endothelial dysfunction in diabetes
The Specific aims of this project are:
1. Characterize the effects of hyperglycemia on vascular reactivity in the cerebral microcirculation
2. Determine the roles of free radicals and protein kinase C in hyperglycemia-induced alteration of vascular reactivity
3. Investigate the effects of hyperglycemia on the regulation of nitric oxide synthase 

Vascular dysfunction in diabetes
The Specific Aims of this project are:
1. To evaluate assessed the effect of streptozotocin-induced diabetes on vascular reactivity
2. To evaluate the different vascular relaxation mechanisms in diabetes
3. To evaluate the interactions of the relaxation mechanisms on endothelial dysfunction in diabetes 

Cellular mechanisms involved in diabetes-induced changes in the brain
Specific Aims:
1: Characterize effects of diabetes on temporal expression of NOS, ET-1, PKC, NAD(P)H, NF-kB proteins
2: Determine temporal changes in cerebrovascular structure following diabetes
3: Investigate the cellular mechanism(s) by which diabetes alters cerebrovascular integrity

Effect of PPAR induction on glycerol-induced acute renal failure (ARF)
Specific Aims
1. a) To determine the role of PPAR in glycerol-induced ARF
b) To investigate the relation between free radicals/antioxidants and PPAR in ARF
2. a) To investigate the interaction between PPAR and renal micro-vascular reactivity to AII and TxA2 in ARF.
b) To determine the effects of PPAR activation on renal vascular AII and TxA2 production, receptor-protein expression in ARF. 

Interaction of PPAR , NAD(P)H oxidase and nitric oxide in glycerol-induced acute renal failure
Specific Aims
1) To establish the role of PPAR and PPAR in vascular aging.
2)  To investigate the affect of PPAR induction in the prevention of oxidative stress-induced vascular aging

Transcriptional regulation of vascular aging
Specific Aims
1) To establish the role of PPAR and PPAR in vascular aging
2)  To investigate the affect of PPAR induction in the prevention of oxidative stress-induced vascular aging