Thromboxane is required for full expression of angiotensin hypertension in rats.
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 endogenous 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 i.v. 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 i.v. 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 i.v. 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 i.v.). 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.
Keen
H L
HL
Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson 39216-4505, USA.
Brands
M W
MW
Smith
M J
MJ
Shek
E W
EW
Hall
J E
JE
D000804:Angiotensin II / Q000008:administration & dosage / Q000097:blood* / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006973:Hypertension / Q000097:blood / Q000209:etiology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000097:blood; D013929:Thromboxane B2 / Q000652:urine; D013931:Thromboxanes / Q000502:physiology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D013931:Thromboxanes; D000804:Angiotensin II; D013929:Thromboxane B2; D012083:Renin