Curt D Sigmund, PhD

curt-sigmund
Internal Medicine, Cardiology
Professor, Roy J. Carver Chair in Hypertension Research
Summary statement: 

Neural Control of Blood Pressure Regulation

Office phone: 
(319) 335-7604
Office number: 
3181B
Office building: 
MERF

The mechanism controlling cell-specific Ang-II production in the brain remains unclear despite evidence supporting neuron-specific reninand glial- and neuronal-specific angiotensinogen expression. We generated double transgenic mice (termed SRA) expressing human renin (hREN) rom a neuron-specific promoter and human angiotensinogen (hAGT) from its own promoter to emulate this expression. SRA mice exhibited an increase in water and salt intake and urinary volume which was significantly reduced after chronic intracerebroventricular delivery of Losartan. Ang-II-like immunoreactivity was markedly increased in the subfornical organ (SFO). To further evaluate the physiological importance of de novo Ang-II production specifically in the SFO, we utilized a transgenic mouse model expressing a "floxed" version of hAGTflox so deletions could be induced with Cre-recombinase. We targeted SFO- specific ablation of hAGTflox by microinjection of an adenovirus encoding Cre-recombinase AdCre). SRA flox mice exhibited a marked increase in drinking at baseline and a significant decrease in water intake after AdCre/AdeGFP, but not after AdeGFP alone. This decrease only occurred when Cre-recombinase correctly targeted the SFO and correlated with a loss of hAGT and angiotensin peptide immunostaining in the SFO. These data provide strong genetic evidence implicating de novo synthesis of Ang-II in the SFO as an integral player in fluid homeostasis. The results of this study published in the Journal of Clinical Investigation (117:1088-1095, 2007) was the topic of an editorial in the journal and illustrates how we use a combination of high tech genetics, genetic techniques and integrative physiology to make fundamental discoveries on the neural control of blood pressure regulation.

“What convinced me to attend Iowa was the Neuroscience Program. There's a deep commitment to neuroscience research at the University of Iowa, and it's reflected in the strength of the Neuroscience Program. Annually, it's ranked as one of the highest doctoral programs at the university, and the ongoing research conducted by the faculty and students is excellent. The interdisciplinary aspect of the program is tremendous for one's graduate education. There's a conflux of molecular/cellular, cognitive, systems, and behavioral research in the program and it really allows each student in the program to gain a broad spectrum of skills and knowledge in the field of neuroscience. But, the program was also attractive to me for reasons outside of the curriculum and research. From the moment I arrived on campus, the program has felt like a family. Students help each other out, and offer a great support system. And after several years of being in the program, I can undoubtedly say, Iowa was the perfect choice for me.”