Angiotension II (ANG II) increases the generation of
vasoconstrictor prostaglandin endoperoxides (
PGH2) and
thromboxane A2 (TxA2). Two-kidney, one-
clip (2K,1C) Goldblatt hypertensive rats have an increased plasma
renin activity (PRA) and ANG II level during the early, but not the late, phases of
hypertension. Therefore, the aim of these studies was to compare the
antihypertensive 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 (20 mg.kg-1.day-1), the TxA2/
PGH2 receptor antagonist
ifetroban (20 mg.kg-1.day-1) or vehicle given for 3 days to rats with early (2-4 wk postclip), intermediate (10-12 wk postclip), and late (36-42 wk 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 mean arterial pressure (MAP) was measured directly with indwelling arterial cannulas. 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 it was increased further to 162 +/- 5 mmHg during the intermediate and to 179 +/- 4 mmHg during the late phase. The PRA, compared with 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 PRA.