Andreas Rohrwasser, Ph.D.
Research Assistant Professor,
Department of Human Genetics

Contribution to Society

Hypertension (HTN) affects over 30% of the US population or 65 million individuals. Despite the target of 50% set by the Healthy People 2010 initiative, only about 30% of patients have their blood pressure under control. This low efficiency in part reflects limited understanding of the relative contributions and nature of the pathways that regulate vascular compliance, tone, and/or volume to the mechanism of essential HTN or HTN of unknown cause.

Genetic studies in patients with essential HTN strongly implicate angiotensinogen and the renin-angiotensin system (RAS) in the pathophysiology of the disease. The discovery of a novel RAS in the renal tubule defined the molecular hypothesis that this system potentially mediates disease progression of volume dependent HTN. Understanding underlying molecular mechanisms will not only refine clinical diagnosis, but will also lead to refined pharmacologic intervention, and improved clinical disease management.

Research Summary

The discovery of angiotensinogen secretion by renal proximal tubules, its presence in final urine, and renin expression and secretion in the connecting segment of the tubule defined the following research goals:

1. Renin regulation in the connecting tubule

In this project, we investigate the molecular mechanisms of renin regulation in the connecting tubules applying in vivo and ex vivo approaches. We will focus on the “sensing” events leading to transcriptional activation and also investigate the mechanisms of renin secretion.

2. Intratubular reaction between angiotensinogen and renin

In the second project we test a) if and b) how filtered and/or secreted renin contributes to increased sodium retention and volume mediated forms of hypertension.

Selected Publications

1. Miller, R.L., et al., Automated Method for the Isolation of Collecting Ducts. Am J Physiol Renal Physiol, 2006.

2. Lantelme, P., et al., Significance of urinary angiotensinogen in essential hypertension as a function of plasma renin and aldosterone status. J Hypertens, 2005. 23(4): p. 785-92.

3. Gociman, B., et al., Expression of angiotensinogen in proximal tubule as a function of glomerular filtration rate. Kidney Int, 2004. 65(6): p. 2153-60.

4. Rohrwasser, A., et al., Renin and kallikrein in connecting tubule of mouse. Kidney Int, 2003. 64(6): p. 2155-62.

5. Lantelme, P., et al., Effects of dietary sodium and genetic background on angiotensinogen and Renin in mouse. Hypertension, 2002. 39(5): p. 1007-14.

6. Lalouel, J.M., et al., Angiotensinogen in essential hypertension: from genetics to nephrology. J Am Soc Nephrol, 2001. 12(3): p. 606-15.

7. Lalouel, J.M. and A. Rohrwasser, Development of genetic hypotheses in essential hypertension. J Hum Genet, 2001. 46(6): p. 299-306.

8. Rohrwasser, A., et al., Elements of a paracrine tubular renin-angiotensin system along the entire nephron. Hypertension, 1999. 34(6): p. 1265-74.