From the Division of Nephrology, Department of Internal Medicine,
Buddhist Tzu Chi General Hospital (T.-C.F.); and the Graduate Institute of
Medical Science, Tzu Chi College of Medicine (T.-C.F., W.-C.H.), Hualien,
Taiwan, Republic of China.
Abstract—The study was conducted to
examine the effects of the angiotensin subtype 1 and 2
receptor antagonists (losartan and PD123319,
respectively) on blood pressure (BP) and renal excretory function in
chronic hyperinsulinemia–induced hypertension in
rats. Hyperinsulinemia was achieved by insulin
infusion (21.5 pmol/kg per minute) via osmotic minipump for 6 weeks.
Losartan or PD123319 was coinfused either at the beginning or
after 4 weeks of insulin infusion. The results showed that insulin
infusion significantly increased the plasma insulin concentration from
259.0±22.2 to 646.5±33.0 and 713.9±26.5 pmol/L
(P<0.05) by the end of the fourth and sixth weeks,
respectively, after insulin infusion. There were no significant changes
in plasma glucose and triglyceride concentrations.
Systolic BP increased from 139±3 to 156±1 and 157±2
mm Hg (P<0.05) at the corresponding time points.
Combined losartan (3.5 µg/kg per minute) and insulin infusion
prevented the rise in BP and improved insulin resistance. When
hypertension had been established after 4 weeks of insulin infusion,
superimposed infusion of losartan on insulin reversed the
elevated BP to control levels within 1 week. In contrast,
administration of PD123319 (0.5 and 10 µg/kg per minute) failed to
alter insulin-induced hypertension. Combined PD123319 with
losartan did not alter the losartan-induced hypotensive
effect in insulin-infused rats. There were no significant differences
in water intake, urine flow, body weight gain, and sodium gain before
and after antagonist administration among groups. These
results indicate that angiotensin type 1 receptors play a
determinant role in the pathogenesis of insulin-induced hypertension
in rats.
© 1998 American Heart Association, Inc.
Scientific Contributions
Angiotensin Receptor Blockade Blunts Hyperinsulinemia-Induced Hypertension in Rats
Key Words: hyperinsulinemia • insulin resistance • losartan • PD123319 • angiotensin receptor antagonist
This article has been cited by other articles:
 |
|
 |
|
  M. E. Johansson, I. J. Andersson, C. Alexanderson, O. Skott, A. Holmang, and G. Bergstrom Hyperinsulinemic rats are normotensive but sensitized to angiotensin II Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2008; 294(4): R1240 - R1247. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Tiwari, V. K.M. Halagappa, S. Riazi, X. Hu, and C. A. Ecelbarger Reduced Expression of Insulin Receptors in the Kidneys of Insulin-Resistant Rats J. Am. Soc. Nephrol., October 1, 2007; 18(10): 2661 - 2671. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Kobayashi, Y. Hayashi, K. Taguchi, T. Matsumoto, and K. Kamata ANG II enhances contractile responses via PI3-kinase p110{delta} pathway in aortas from diabetic rats with systemic hyperinsulinemia Am J Physiol Heart Circ Physiol, August 1, 2006; 291(2): H846 - H853. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Song, X. Hu, S. Riazi, S. Tiwari, J. B. Wade, and C. A. Ecelbarger Regulation of blood pressure, the epithelial sodium channel (ENaC), and other key renal sodium transporters by chronic insulin infusion in rats Am J Physiol Renal Physiol, May 1, 2006; 290(5): F1055 - F1064. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-C. Juan, Y.-W. Shen, Y. Chien, Y.-J. Lin, S.-F. Chang, and L.-T. Ho Insulin infusion induces endothelin-1-dependent hypertension in rats Am J Physiol Endocrinol Metab, November 1, 2004; 287(5): E948 - E954. [Abstract] [Full Text] [PDF]
|
|