Published online before print September 12, 2002, doi: 10.1161/01.RES.0000036749.73316.73
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on April 25, 2002
Revised on August 29, 2002
Accepted on August 29, 2002
Hypertension-Linked Decrease in the Expression of Brain 
-Adducin
Hong Yang ;
From the Department of Physiology and Functional Genomics (H.Y., S.C.F., K.S., M.D., C. Sun, C. Sumners, M.K.R.) College of Medicine and University of Florida McKnight Brain Institute, Gainesville, Fla; the Department of Pharmacodynamics (M.J.K.), College of Pharmacy, University of Florida, Gainesville, Fla; The Hypertension and Vascular Disease Center (C.M.F.), Wake Forest University School of Medicine, Winston-Salem, NC; and the International Center for Genetic Engineering and Biotechnology (A.F.M.), Trieste, Italy.
* To whom correspondence should be addressed. E-mail: mraizada{at}phys.med.ufl.edu.
Gene profiling data coupled with adducin polymorphism studies led us to hypothesize that decreased expression of this cytosolic protein in the brain could be a key event in the central control of hypertension. Thus, our objectives in the present study were to (1) determine which adducin subunit gene demonstrates altered expression in the hypothalamus and brain stem (two cardioregulatory-relevant brain areas) in two genetic strains of hypertensive rats and (2) analyze the role of adducins in neurotransmission at the cellular level. All three adducin subunits (
, ß, and 
) were present in the hypothalamus and brain stem of Wister Kyoto (WKY) and spontaneously hypertensive (SH) rats. However, only the -adducin subunit expression was 40% to 60% lower in the SH rat compared with WKY rat. A similar decrease in -adducin expression was observed in the hypothalamus and brain stem of the renin transgenic rat compared with its normotensive control. Losartan treatment of the SH rat failed to normalize -adducin gene expression. A hypertension-linked decrease of -adducin was confirmed by demonstrating a decrease in -adducin expression in hypothalamic/brain stem neuronal cultures from prehypertensive SH rats. Neuronal firing rate was evaluated to analyze the role of this protein in neurotransmission. Perfusion of a -adducin-specific antibody caused a 2-fold increase in the neuronal firing rate, an effect similar to that observed with angiotensin II. Finally, we observed that preincubation of neuronal cultures for 8 hours with 100 nmol/L angiotensin II caused a 60% decrease in endogenous -adducin and was associated with a 2-fold increase in basal firing rate. These observations support our hypothesis that a decrease in -adducin expression in cardioregulatory relevant brain areas is linked to hypertension possibly by regulating the release of neurotransmitters.
Key words: hypothalamus • brain stem • gene profiling • neurons •
-adducin
This article has been cited by other articles:
 |
|
 |
|
  G. Bianchi Genetic variations of tubular sodium reabsorption leading to "primary" hypertension: from gene polymorphism to clinical symptoms Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2005; 289(6): R1536 - R1549. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Bianchi, P. Ferrari, and J. A. Staessen Adducin Polymorphism: Detection and Impact on Hypertension and Related Disorders Hypertension, March 1, 2005; 45(3): 331 - 340. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Yang, P. Y. Reaves, M. J. Katovich, and M. K. Raizada Decrease in Hypothalamic Gamma Adducin in Rat Models of Hypertension Hypertension, February 1, 2004; 43(2): 324 - 328. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Sun, J. Du, C. Sumners, and M. K. Raizada PI3-Kinase Inhibitors Abolish the Enhanced Chronotropic Effects of Angiotensin II in Spontaneously Hypertensive Rat Brain Neurons J Neurophysiol, November 1, 2003; 90(5): 3155 - 3160. [Abstract] [Full Text] [PDF]
|
|