At1 and txa2/pgh2 receptors maintain hypertension throughout 2k, 1c
goldblatt hypertension in the rat.
Wilcox, Christopher S., James Cardozo, and William J. Welch.
Division of Nephrology and Hypertension, Georgetown University
Medical Center, Washington, DC
APStracts 3:0095R, 1996.
Angiotensin II (Ang II) increases the generation of vasoconstrictor
prostaglandin endoperoxides (PGH2) and thromboxane A2 (TxA2). Two
kidney, 1 clip (2K, 1C) Goldblatt hypertensive rats have an increased
plasma renin activity (PRA) and angiotensin II (Ang II) level during
the early, but not the late phases of hypertension. Therefore, the
aim of these studies was to compare the anti-hypertensive efficacy of
an Ang II type I (AT1) and a TxA2/PGH2 receptor antagonist during
different phases of 2K, 1C hypertension. Rats were maintained on a
fixed sodium intake for 3 days before and throughout the period of
drug administration. These studies assessed the antihypertensive
response to administration of the AT1 receptor antagonist losartan
(20mg x kg-1 x d-1), the TxA2/PGH2 receptor antagonist ifetroban
(20mg x kg-1 x d-1) or vehicle given for 3 days to rats with early (2
to 4 weeks post-clip), intermediate (10 to 12 weeks post-clip), and
late (36 to 42 weeks post-clip) 2K, 1C hypertension and to two
control groups of rats corresponding in age to the early or
intermediate and the late 2K, 1C groups. The MAP was measured
directly with indwelling arterial cannulae. The MAP of sham-operated
rats was 109 +/- 5 mmHg. In the early phase of 2K, 1C hypertension,
the MAP was increased to 143 +/- 6 mmHg and increased further to 162
+/- 5 mmHg during the intermediate and to 179 +/- 4 mmHg during the
late phase. The PRA, compared to age-matched controls was increased
during early and intermediate, but not late phase 2K, 1C
hypertension. Neither drug lowered blood pressure in control rats.
However, both drugs significantly reduced the blood pressure in the
early, intermediate and late phases of 2K, 1C hypertension. At the
end of 3 days of administration, blood pressure in early 2K, 1C rats
given losartan was reduced to levels of control rats, but remained
slightly elevated in other groups and in those receiving ifetroban.
In conclusion, AT1 and TxA2/PGH2 receptors maintain hypertension
throughout the evolution of 2K, 1C hypertension in the rat, despite
changes in plasma renin activity.
Received 29 September 1995; accepted in final form 4 March 1996.
APS Manuscript Number R618-5.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 20 March 96