Renal Physiology, Cardiovascular Physiology, and Genetics & Genomics

Mechanisms controlling blood flow to the renal medulla. Studies in our laboratory have found that reductions of medullary blood flow result in excess retention of sodium and water and lead to hypertension. Our work is now directed toward understanding the mechanisms that normally control renal medullary blood flow and how alterations in these pathways can lead to hypertension. We are looking at medullary production of reactive oxygen species within the tubules that surround the microcirculation, to determine how nitric oxide and superoxide produced in these tubules can signal changes in the regional blood flow. Other studies in our lab are directed to understanding the role of excess production of superoxide and hydrogen peroxide within a genetic rat model of salt-sensitive hypertension.

Impact of arterial pressure on the production of oxidative stress and renal injury in the renal medulla of hypertensive rats. We are conducting studies on chronically instrumented rats, in which the arterial pressure to a single kidney can be controlled at a normal level during the development of hypertension while the other kidney is exposed to the effects of the high arterial pressure. Computer controlled inflation of an aortic balloon occluder implanted on the aortic between the upper right renal artery and lower left renal artery controls these pressures over several weeks. Immunohistochemical techniques and microarray studies determine what pathways are initiated by the elevated pressure that lead to interstitial fibrosis within the hypertensive kidney.

Determine the genetic and physiological basis of protection from salt-induced hypertension resulting from the introgression of chromosome 13 from a normal BN rat into the Dahl salt-sensitive rat. We have developed 26 overlapping congenic Dahl salt-sensitive rat strains, each with a small piece of the BN chromosome 13 substituted into the Dahl salt-sensitive chromosome 13. These studies will use gene microarrays as a powerful assay system to test specific hypotheses about how genetic pathways and networks are linked to whole system physiology and the progression of hypertension. Genes differentially expressed within the small congenic regions that are associated with a protective effect from salt-induced hypertension will be further identified by positional cloning approaches.

Source:  http://www.phys.mcw.edu/fac_cowley.htm