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(Hypertension. 1997;29:310.)
© 1997 American Heart Association, Inc.

Arthur C. Corcoran Memorial Lecture

Thromboxane Is Required for Full Expression of Angiotensin Hypertension in Rats

Henry L. Keen; Michael W. Brands; Manis J. Smith, Jr; Eugene W. Shek; John E Hall

From the Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson.

Correspondence to Michael W. Brands, PhD, Department of Physiology and Biophysics, University of Mississippi Medical Center, 2500 North State St, Jackson, MS 39216-4505

Recent studies suggest that thromboxane (TX) mediates a significant component of angiotensin II (ANG II)- induced hypertension. However, there is little information to support the hypothesis that this relationship is important during chronic, physiological increases in ANG II, particularly while controlling for variation in endogeneous ANG II levels induced by TX inhibition. This study tested that hypothesis in 27 chronically instrumented rats. After baseline measurements, suppression of endogenous TX was induced and maintained throughout the study in 13 rats by IV infusion of the TX synthesis inhibitor (TSI) U63557A; the other 14 rats received vehicle. Baseline mean arterial pressure (MAP) was not different between groups and was unchanged by TSI or vehicle. Continuous inhibition of ANG II production was then initiated in both groups of rats by IV infusion of the angiotensin-converting enzyme inhibitor (ACEI) benazepril. ACEI reduced blood pressure similarly in vehicle 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·min^-1 IV for 7 days in six rats from each group to restore ANG II activity to baseline levels. This dose increased MAP to 103±2 and 101±1 mm Hg in vehicle and TSI rats, respectively, values not different from pre-ACEI levels. Seven TSI rats and eight vehicle rats received 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 determinant of MAP in ANG II hypertension but may have a diminished role in blood pressure regulation when ANG II is at normal and subnormal levels.

Key Words: angiotensin II • thromboxane • blood pressure • hypertension

Abbreviations: ANG = angiotensin • TX = thromboxane • TSI = TX synthesis inhibitor • MAP = mean arterial pressure • ACE = angiotensin-converting enzyme • GFR = glomerular filtration rate • PRA = plasma renin activity • PG = prostaglandin • ACEI = ACE inhibitor • TGF = tubuloglomerular feedback

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