Grant: $223,569 - National Institutes of Health - Jul. 16, 2009
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Award Description: This supplement is designed to provide salary and research funds for hiring of a post-doctoral fellow to support the recently funded, new investigator grant 5R01HL088421-02 entitled 'The Renal Medulla and Hypertension.' The post doctoral fellow (Dr. Eva Csongradi) hired for this research proposed in this application is significant because it will provide new insights into a novel mechanism for reducing blood pressure in hypertension. Hypertension occurs in over 50 million adults in the U.S. The risk of developing hypertension during the remaining years of life for non-hypertensive adults aged 55 years has also been estimated to be approximately 60-90%. In addition, at least two million children and adolescents have hypertension. Hypertension is a major risk factor for a number of diseases including stroke, heart failure, coronary artery disease, peripheral vascular disease, and chronic renal failure. The economic impact of this silent killer is tremendous, running into the billions of dollars each year. The Project has 2 specific aims which are as follows: Specific Aim 1: to test the hypothesis that chronic decreases in renal medullary HO-1 levels enhance and chronic induction of renal medullary HO-1 attenuates Ang II mediated increase in NADPH oxidase and superoxide production in the renal medulla. Specific Aim 2: To test the hypothesis that the HO-1 metabolite bilirubin is essential in buffering Ang II-mediated increases in NADPH oxidase, superoxide production and blood pressure.
Project Description: We have performed studies in which a novel imidazole-dioxolane heme oxygenase inhibitor has been infused in the renal medulla of mice. This inhibitor, QC-13, is a specific inhibitor of HO-1 activity in the medulla. We have performed studies in mice pretreated with the HO-1 inducer, cobalt protporphyrin (CoPP). After induction of HO-1 with CoPP, QC-13 was infused into the renal medulla for 2 days and then the levels of HO activity and protein were measured. We found that infusion of QC-13 into the renal medulla of mice treated with CoPP inhibited medullary HO activity by 64% as compared to vehicle infused mice. We did not observe any decrease in renal cortical HO activity in mice receiving intramedullary interstitial infusion of QC-13. Classical porphyrin based HO inhibitors have been found to significant induce HO-1 protein levels in vivo which complicates their use. In contrast to the classical porphyrin based inhibitors, we found no induction of HO-1 in mice chronically infused with QC-13 at this concentration. We are now performing experiments in Specific Aim #1 in which QC-13 will be used to determine if decreases in HO-1 activity enhances Ang II mediated superoxide production and augments Ang II mediated increases in blood pressure.
Jobs Summary: no jobs created (Total jobs reported: 0)
Project Status: Less Than 50% Completed
This award's data was last updated on Jul. 16, 2009. Help expand these official descriptions using the wiki below.