Renal Physiology Research at the Medical College of Wisconsin

Renal physiology research in the Department of Physiology at MCW is primarily focused on the importance of renal blood flow and renal function in the regulation of arterial blood pressure. Research addressing this area is done on every level from in vivo to in vitro to the genetic dissection of hypertension.

Our studies have found that reductions of medullary blood flow result in excess retention of sodium and water, which leads 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. Other studies are designed to determine the genetic and physiological basis of protection from salt-induced hypertension resulting from the introgression of chromosome 13 from a normal Brown Norway rat into a Dahl salt-sensitive rat. These studies 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.

In other departmental research, particular emphasis is placed on the paracrine, autocrine, and hormonal regulation of renal tubular and vascular function. Studies utilize in vitro measurements of mRNA, protein, enzymatic activity, enzyme kinetics, and cell signaling as well as in vivo measurements of hormone levels, blood flow, blood pressure, and other indices of renal/cardiovascular function in anesthetized and conscious rats and mice. Experimental models include various strains of inbred and genetically manipulated rats and mice.

Another research focus is the role of P450 eicosanoids in the control of renal tubular transport and vascular function and the molecular genetics of hypertension. The techniques we are using include micropuncture and isolated perfused tubule studies of single nephron function, studies in isolated perfused vessels, patch clamp studies of Ca and K channel activity in smooth muscle, biochemical analysis of eicosanoids, IP3, PKC, DAG and other signaling molecules, Northern and Western blots, PCR molecular cloning, DNA sequencing, transient expression studies in cultured cells, and in vivo. Genetic mapping, expression profiling and physiologic profiling are also used to search for genes contributing to the development of hypertension, glomerulosclerosis and diabetes.