| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Hypertension. 1999;33:219-224.)
© 1999 American Heart Association, Inc.
Scientific Contributions |
Atrial Natriuretic Peptide Gene Delivery Reduces Stroke-Induced Mortality Rate in Dahl Salt-Sensitive Rats
From the Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston.
Correspondence to Lee Chao, PhD, Department of Biochemistry and Molecular Biology, 171 Ashley Ave, Charleston, SC 29425. E-mail chaol{at}musc.edu
Abstract—Atrial natriuretic peptide (ANP) is a powerful hormone with hypotensive, natriuretic, diuretic, and many other beneficial effects. Direct infusion of ANP in therapeutics has limited success because of its short half-life in the circulation. Our previous studies have shown that ANP gene delivery attenuates hypertension, cardiac hypertrophy, and renal injury in Dahl salt-sensitive (Dahl-SS) rats. To investigate the potential therapeutic value of ANP gene delivery on salt-induced stroke and cerebrovascular disorders, an adenovirus harboring the human ANP gene (Ad.RSV-cANP) was injected into Dahl-SS rats on a high salt diet. A single intravenous injection of the ANP gene caused a significant reduction of blood pressure that lasted for more than 3 weeks. A maximal blood pressure reduction of 28 mm Hg was observed 2 weeks after gene delivery as compared with that of control rats injected with adenovirus harboring the LacZ gene under the control of the Rous sarcoma virus promoter (Ad.RSV-LacZ). Immunoreactive human ANP can be detected in the heart, lung, kidney, and brain of rats after gene delivery. The stroke mortality rate of Dahl-SS rats was significantly decreased (from 54% to 17% at 3 weeks and from 70% to 50% at 4 weeks after ANP gene delivery as compared with rats injected with control virus). ANP gene delivery also significantly attenuates salt-induced aortic hypertrophy as evidenced by reduced thickness of the aortic wall. This is the first study to demonstrate the potential of ANP gene delivery in reducing the mortality rate caused by cerebrovascular disorders and stroke. Successful application of this technology may have potential value in treating individuals with a high risk of stroke.
Key Words: gene delivery • rats, Dahl • adenovirus • blood pressure • hypertrophy, aortic • stroke
This article has been cited by other articles:
 |
|
 |
|
  J.-P. Therrien, W. Pfutzner, and J. C. Vogel An Approach to Achieve Long-Term Expression in Skin Gene Therapy Toxicol Pathol, January 1, 2008; 36(1): 104 - 111. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. J. Schillinger, S. Y. Tsai, G. E. Taffet, A. K. Reddy, A. J. Marian, M. L. Entman, K. Oka, L. Chan, and B. W. O'Malley Regulatable atrial natriuretic peptide gene therapy for hypertension PNAS, September 27, 2005; 102(39): 13789 - 13794. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. H. Kim, K. A. Skelding, E. G. Nabel, and R. D. Simari What can cardiovascular gene transfer learn from genomics: and vice versa? Physiol Genomics, December 3, 2002; 11(3): 179 - 182. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Massfelder, N. Taesch, S. Fritsch, A. Eichinger, M. Barthelmebs, A. F. Stewart, and J.-J. Helwig Type 1 Parathyroid Hormone Receptor Expression Level Modulates Renal Tone and Plasma Renin Activity in Spontaneously Hypertensive Rat J. Am. Soc. Nephrol., March 1, 2002; 13(3): 639 - 648. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Hassan, N. Ali, Y. Dong, N. D. Carter, and H. S. Markus Atrial natriuretic peptide gene G664A polymorphism and the risk of ischemic cerebrovascular disease Neurology, November 13, 2001; 57(9): 1726 - 1728. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P.R Kalra, S.D Anker, A.D Struthers, and A.J.S Coats The role of C-type natriuretic peptide in cardiovascular medicine Eur. Heart J., June 2, 2001; 22(12): 997 - 1007. [PDF]
|
|
|
|
 |
|
 A. Hassan and H. S. Markus Genetics and ischaemic stroke Brain, September 1, 2000; 123(9): 1784 - 1812. [Abstract] [Full Text] [PDF]
|
|