Oakland University
Sunday, January 9, 2011

Amy Banes-Berceli studies hypertension using knock-out mice

One important tool of modern biology is “knock-out” mice: mice that have been modified genetically to turn off particular genes. Assistant Professor and CBR member Amy Banes-Berceli uses knock-out mice in her studies of the molecular mechanisms of high bood pressure and diabetes. Banes-Berceli, her student Hind Al-Azawi, and a group of collaborators from the Medical College of Georgia led by Michael Brands published a paper describing how “Interleukin 6 Knockout Prevents Angiotensin II Hypertension” in the November issue of Hypertension (Volume 56, Pages 879-884). They write
“Evidence linking inflammatory mechanisms to cardiovascular diseases, such as atherosclerosis and hypertension, continues to build. However, the identity of the precise inflammatory mediators and the mechanisms that underlie their cardiovascular actions remain unclear. The cytokine interleukin 6 (IL-6) is released from vascular tissue in response to angiotensin II (Ang II), and our laboratory showed that acute, stress-induced hypertension, which is Ang II dependent, is attenuated in IL-6 knockout (KO) mice....

The goal of this study was to determine whether an effect of IL-6 on Ang II–mediated renal vasoconstriction could be a potential mechanism for the dependence of Ang II hypertension on IL-6. … We used chronically implanted renal artery flow probes to test the hypothesis that chronic Ang II– induced renal vasoconstriction would be attenuated in IL-6 KO mice.”
Hypertension published an editorial accompanying Banes-Berceli’s paper. The author Michael Ryan writes
“In this issue of Hypertension, Brands et al take an important step in the direction of understanding the mechanism by which IL-6 contributes to Ang II hypertension. Similar to their initial work, blood pressure in the current study was lower in IL-6 knockout mice given Ang II. However, different from results obtained in the former study, the hypertension was completely abolished rather than only blunted. This is most likely because the animals from the former study were maintained on a high-salt diet, in addition to the Ang II. The reason that Ang II is able to increase pressure in IL-6 knockout mice maintained on a high-salt diet is not clear but suggests that some permissive factors or alternative pathways are present during high-salt intake….

The major advance made in the present study comes from data collected during chronic measurements of renal blood flow (RBF) in conscious mice. These results show that Ang II dose-dependently produces a sustained decrease in RBF in wild-type mice. Surprisingly, the RBF response to Ang II in IL-6 knockout mice was similar to the wild-type mice, even as the wild-type animals exhibited the expected hypertension that was otherwise absent in the IL-6 knockout mice. The authors go further to show that afferent arteriolar constriction in response to Ang II is the same between wild-type and IL-6 knockout mice, at least under control conditions. These data are provocative because they raise perhaps as many questions as are answered related to the role that IL-6 plays in Ang II hypertension.”
Banes-Berceli’s laboratory is currently funded by a grant from the National Institutes of Health. Hind Al-Azawi is a graduate student in the Master of Science program in biology. She was also an undergraduate at OU, was a Summer Undergraduate Research Fellow, and has presented her results at the Meeting of Minds and at an International Experimental Biology Meeting in Anahiem, California.
CBR member Amy Banes-Berceli recently published a study of hypertension using genetically engineered knock-out mice.

Created by Brad Roth (roth@oakland.edu) on Sunday, January 9, 2011
Modified by Brad Roth (roth@oakland.edu) on Monday, January 10, 2011
Article Start Date: Sunday, January 9, 2011