THROMBOXANE IS REQUIRED FOR FULL EXPRESSION OF ANGIOTENSIN HYPERTENSION IN RATS

Recent studies suggest that thromboxane (TX) mediates a significant co mponent of angiotensin II (ANG II)-induced hypertension. However, ther e is little information to support the hypothesis that this relationsh ip is important during chronic, physiological increases in ANG II, par ticularly while controlling for variation in endogenous ANG II levels induced by TX inhibition. This study tested that hypothesis in 27 chro nically instrumented rats. After baseline measurements, suppression of endogenous TX was induced and maintained throughout the study in 13 r ats by IV infusion of the TX synthesis inhibitor (TSI) U63557A; the ot her 14 rats received vehicle. Baseline mean arterial pressure (MAP) wa s not different between groups and was unchanged by TSI or vehicle. Co ntinuous inhibition of ANG II production was then initiated in both gr oups of rats by IV infusion of the angiotensin-converting enzyme inhib itor (ACEI) benazepril. ACEI reduced blood pressure similarly in vehic le and TSI rats, from 105 +/- 2 to 91 +/- 2 mm Hg and 103 +/- 1 to 89 +/- 1 mm Hg, respectively. ANG II was then infused at 5 ng . kg(-1). m in(-1) IV for 7 days in six rats from each group to restore ANG II act ivity to baseline levels. This dose increased MAP to 103 +/- 2 and 101 +/- 1 mm Hg in vehicle and TSI rats, respectively, values not differe nt from pre-ACEI levels. Seven TSI rats and eight vehicle rats receive d a higher dose of ANG II (20 ng . kg(-1). min(-1) IV). After 7 days, MAP was higher in vehicle than in TSI rats (143 +/- 5 versus 120 +/- 4 mm Hg). These results suggest that endogenous TX is an important dete rminant of MAP in ANG II hypertension but may have a diminished role i n blood pressure regulation when ANG II is at normal and subnormal lev els.