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(Hypertension. 2003;42:932.)
© 2003 American Heart Association, Inc.
Scientific Contributions |
From the Department of Pharmacology and Toxicology, Queens University (C.S., M.A.A.), Kingston, and the Department of Physiology, University of Western Ontario (R.L.K.), London, Ontario, Canada.
Correspondence to Dr Michael A. Adams, Department of Pharmacology and Toxicology, Queens University, Kingston, Ontario, Canada K7L 3N6. E-mail adams{at}post.queensu.ca
The kidney plays a critical role in regulating the level of arterial pressure and in the pathogenesis of hypertension. Important evidence has come from studies in which hypertension is generated by transplanting kidneys from genetically hypertensive rats into normotensive recipients, suggesting that the level of blood pressure is strongly influenced by the genetic background of the kidney. We hypothesized that pharmacotherapy could modify specific properties intrinsic to the kidney such that after transplantation, there would be persistent changes in the level of arterial pressure. We determined that angiotensin-converting enzyme inhibitor treatment (enalapril) in spontaneously hypertensive rats induced both a persistent 17% reduction of mean arterial pressure and a persistent change in the kidney. This persistent change in the circulation could be completely transferred to untreated spontaneously hypertensive rats by kidney transplantation; ie, mean arterial pressure in untreated spontaneously hypertensive rat recipients was persistently lowered after transplantation of a kidney from a previously treated spontaneously hypertensive rat donor. In addition, the persistent lowering of mean arterial pressure after enalapril treatment could be completely abolished by implanting an untreated kidney, thereby revealing the importance of the kidney-specific changes. Furthermore, after within-group transplantations, there were no changes in the level of arterial pressure; ie, a 16% difference in mean arterial pressure remained between the 2 groups. The findings revealed that drug-induced changes specific to the kidney determined the level of arterial pressure, thereby suggesting the kidney should be a key therapeutic target for pharmacotherapy.
Key Words: transplantation, renal renin-angiotensin system rats, spontaneously hypertensive arterial pressure angiotensin-converting enzyme inhibitors
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