Effect of enalapril or the thromboxane receptor antagonist, daltroban, in rats with subtotal renal ablation.
There is evidence to suggest that thromboxane synthesis inhibition will attenuate the hypertension and proteinuria associated with subtotal renal ablation. In the present study, the thromboxane receptor antagonist, daltroban, (30 mg/kg/day i.p.) or vehicle was administered to rats for 3 weeks starting 2 weeks after partial renal ablation (right uninephrectomy and ligation of approximately two-thirds of the blood supply to the left kidney). Renal ablation was associated with proteinuria and increased systolic blood pressure. Neither the proteinuria nor the hypertension was affected by daltroban administration. Histological examination of the remaining kidney demonstrated no beneficial effect of daltroban. In a second study, it was determined that, 2 weeks after renal ablation, urinary thromboxane excretion was significantly increased, and subsequent administration of daltroban for 2 weeks resulted in significant blockade of the effects of the thromboxane mimetic, U46619. In a third study, enalapril (50 mg/l in the drinking water) resulted in a significant attenuation of the proteinuria, hypertension and glomerular lesions associated with partial renal ablation. The data indicate that enalapril, but not daltroban, protects against the development of renal disease associated with reduced renal mass.
Brooks
D P
DP
Department of Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania.
Contino
L C
LC
Trizna
W
W
Edwards
R M
RM
Ohlstein
E H
EH
Solleveld
H A
HA
D000818:Animals; D004656:Enalapril / Q000494:pharmacology*; D007674:Kidney Diseases / Q000517:prevention & control*; D008297:Male; D009392:Nephrectomy; D010648:Phenylacetates / Q000494:pharmacology*; D011507:Proteinuria / Q000209:etiology; D051381:Rats; D011919:Rats, Inbred Strains; D011982:Receptors, Prostaglandin / Q000187:drug effects*; D017482:Receptors, Thromboxane; D013449:Sulfonamides / Q000494:pharmacology*; D013931:Thromboxanes / Q000037:antagonists & inhibitors*
D010648:Phenylacetates; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D013449:Sulfonamides; D013931:Thromboxanes; D004656:Enalapril; C051762:daltroban