Acute effect of a thromboxane synthetase inhibitor on renal function in unanaesthetized sheep.
1. Eleven healthy, unanaesthetized sheep were given either a single intravenous bolus infusion of U63,577A (Upjohn), a selective thromboxane synthetase inhibitor, at a dose of 30 mg/kg (group 1, n = 6), or vehicle alone (group 2, n = 5). Animals were maintained in metabolic cages during the study, and received 150 ml of water/h and 7.5 mmol of sodium/h as Ringers lactate by intravenous infusion for 24 h before and during the study. During two 1 h control urine collections via bladder catheter, urine volume and sodium excretion closely paralleled these infusion rates. 2. In the first hour after injection of U63,577A, there were significant two- to three-fold increases in urine volume, urinary sodium excretion and fractional sodium excretion, compared with the control collections. During the subsequent 4 h, urine volume, urinary sodium excretion, and fractional sodium excretion fell to values significantly lower than in the control period. Creatinine clearance was reduced 1, 2 and 4 h post injection and returned to control values at 5 h. Urinary excretion of thromboxane B2 was significantly reduced compared with control values during the 5 h after injection of U63,577A. Excretion of 6-keto-prostaglandin F1 alpha did not change. Plasma renin activity was significantly increased 1, 3 and 5 h after injection of U63,577A. Vehicle controls showed no change in any of the above parameters. 3. The results indicate that in healthy conscious sheep, sodium and water replete, U63,577A has a transient but significant diuretic and natriuretic effect, followed by sodium and water retention and increased plasma renin activity.(ABSTRACT TRUNCATED AT 250 WORDS)
Cumming
A D
AD
Department of Medicine, University of Western Ontario, London, Canada.
Lindsay
R M
RM
McDonald
J W
JW
Linton
A L
AL
D000818:Animals; D001572:Benzofurans / Q000494:pharmacology*; D005260:Female; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D012083:Renin / Q000097:blood; D012756:Sheep; D012890:Sleep / Q000502:physiology*; D012964:Sodium / Q000502:physiology; D013928:Thromboxane A2 / Q000502:physiology; D013929:Thromboxane B2 / Q000652:urine; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*; D014563:Urodynamics / Q000187:drug effects
D001572:Benzofurans; D013929:Thromboxane B2; D013928:Thromboxane A2; D012964:Sodium; D012083:Renin; D013930:Thromboxane-A Synthase; C039936:furegrelate