Effects of acute systemic at1 receptor blockade by candesartan on
arterial pressure and renal function in anesthetized rats..
Cervenka, Ludek, Chi-Tarng Wang, and L. Gabriel Navar.
Tulane University School of Medicine, Department of Physiology
SL39, 1430 Tulane Avenue, New Orleans, LA. 70112, USA
APStracts 5:0033F, 1998.
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 (ANGII) and on renal hemodynamics and sodium
excretion. Control arterial pressure responses to bolus ANGII doses
of 10, 50, 100 and 1000 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
per cent. The vasoconstrictor responses to ANGII up to 1000 ng were
completely blocked by Candesartan doses of 1 and 0.1 mg/kg while
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 1mg/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) per cent. The inability to
overcome blockade even with very high ANGII doses indicates that
Candesartan is a potent noncompetitive blocker of ANGII pressor and
renal vasoconstrictor effects. The lower Candesartan dose that did
not cause significant hypotension, elicited substantial increases in
renal blood flow, GFR and sodium excretion revealing the direct renal
vasodilator and natriuretic effects of AT1 receptor blockade.
Received 2 September 1997; accepted in final form 2 February
1998.
APS Manuscript Number F283-7.
Article publication pending Am. J. Physiol. (Renal Physiology).
ISSN 1080-4757 Copyright 1998 The American Physiological Society.
Published in APStracts on 19 February 1998