| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Department of Physiology, Tulane University School of Medicine, New Orleans, Louisiana 70112
Experiments were performed on normal anesthetized rats to determine the effects of candesartan, a novel AT1 receptor antagonist, on the arterial pressure and renal hemodynamic responses to bolus doses of angiotensin II (ANG II) and on renal hemodynamics and sodium excretion. Control arterial pressure responses to bolus ANG II doses of 10, 50, 100 and 1,000 ng were 26 ± 6, 54 ± 7, 57 ± 7, and 79 ± 7 mmHg; the decreases in cortical renal blood flow (CRBF), measured with laser-Doppler flowmetry, were 47 ± 9, 64 ± 8, 71 ± 6, and 82 ± 6%. The vasoconstrictor responses to ANG II up to 1,000 ng were completely blocked by candesartan doses of 1 and 0.1 mg/kg, whereas treatment with 0.01 mg/kg candesartan attenuated the arterial pressure and CRBF responses. The higher doses of candesartan (1 and 0.1 mg/kg) elicited rapid decreases in arterial pressure, leading to associated decreases in sodium excretion. Renal blood flow (RBF), glomerular filtration rate (GFR), and urine flow also decreased following treatment with candesartan at 1 mg/kg. In contrast, when candesartan was given at 0.01 mg/kg, which did not decrease arterial pressure significantly, there were significant increases in GFR (16 ± 4), RBF (9 ± 2), urine flow (11 ± 2), sodium excretion (35 ± 7), and fractional sodium excretion (39 ± 8%). The inability to overcome blockade, even with very high ANG II doses, indicates that candesartan is a potent noncompetitive blocker of ANG II pressor and renal vasoconstrictor effects. The lower candesartan dose that did not cause significant hypotension elicited substantial increases in RBF, GFR, and sodium excretion, revealing the direct renal vasodilator and natriuretic effects of AT1 receptor blockade.
AT1 receptor blockade; glomerular filtration rate; renal blood flow; sodium excretion
This article has been cited by other articles:
|
|
 |
|
  A. Eskild-Jensen, L. F. Paulsen, L. Wogensen, P. Olesen, L. Pedersen, J. Frokiaer, and J. R. Nyengaard AT1 receptor blockade prevents interstitial and glomerular apoptosis but not fibrosis in pigs with neonatal induced partial unilateral ureteral obstruction Am J Physiol Renal Physiol, June 1, 2007; 292(6): F1771 - F1781. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Franco, F. Martinez, B. Rodriguez-Iturbe, R. J. Johnson, J. Santamaria, A. Montoya, T. Nepomuceno, R. Bautista, E. Tapia, and J. Herrera-Acosta Angiotensin II, interstitial inflammation, and the pathogenesis of salt-sensitive hypertension Am J Physiol Renal Physiol, December 1, 2006; 291(6): F1281 - F1287. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. A. Banday, A. H. Siddiqui, M. M. Menezes, and T. Hussain Insulin treatment enhances AT1 receptor function in OK cells Am J Physiol Renal Physiol, June 1, 2005; 288(6): F1213 - F1219. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T.-H. Kwon, J. Nielsen, M. A. Knepper, J. Frokiaer, and S. Nielsen Angiotensin II AT1 receptor blockade decreases vasopressin-induced water reabsorption and AQP2 levels in NaCl-restricted rats Am J Physiol Renal Physiol, April 1, 2005; 288(4): F673 - F684. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. C. F. Sandgaard, J. L. Andersen, N.-H. Holstein-Rathlou, and P. Bie Aortic blood flow subtraction: an alternative method for measuring total renal blood flow in conscious dogs Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2002; 282(5): R1528 - R1535. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Andersen, N. C. F. Sandgaard, and P. Bie Volume expansion during acute angiotensin II receptor (AT1) blockade and NOS inhibition in conscious dogs Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2002; 282(4): R1140 - R1148. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Feraille and A. Doucet Sodium-Potassium-Adenosinetriphosphatase-Dependent Sodium Transport in the Kidney: Hormonal Control Physiol Rev, January 1, 2001; 81(1): 345 - 418. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Omoro, D. S. A. Majid, S. S. El Dahr, and L. G. Navar Roles of ANG II and bradykinin in the renal regional blood flow responses to ACE inhibition in sodium-depleted dogs Am J Physiol Renal Physiol, August 1, 2000; 279(2): F289 - F293. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. CERVENKA, K. D. MITCHELL, and L. G. NAVAR Renal Function in Mice: Effects of Volume Expansion and AngiotensinII J. Am. Soc. Nephrol., December 1, 1999; 10(12): 2631 - 2636. [Abstract] [Full Text]
|
|
|
|
|
|
K. Brannstrom and W. J. Arendshorst Resetting of exaggerated tubuloglomerular feedback activity in acutely volume-expanded young SHR Am J Physiol Renal Physiol, March 1, 1999; 276(3): F409 - F416. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. O. Krebs, T. Krohn, W. Boemke, R. Mohnhaupt, and G. Kaczmarczyk Renal and hemodynamic effects of losartan in conscious dogs during controlled mechanical ventilation Am J Physiol Renal Physiol, March 1, 1999; 276(3): F425 - F432. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
