Prolonged bleeding time and increased vascular prostacyclin in rats with chronic renal failure: effects of conjugated estrogens.
The aim of our study was to assess whether the development of chronic uremia in rats with extensive renal mass ablation was associated with an impairment of primary hemostasis as occurs in humans with terminal uremia. We also wanted to assess whether uremic rats had an increased generation of vascular prostacyclin (PGI2) and whether conjugated estrogens could influence such an abnormality. Our results showed that the development of chronic renal failure in rats was associated with a significant prolongation of bleeding time as reported in humans. Thoracic aorta and inferior vena cava specimens from uremic rats produced significantly more 6-keto-prostaglandin F1 alpha (the stable breakdown product of PGI2) than did specimens from the corresponding controls. Conjugated estrogens significantly shortened the bleeding time of uremic rats. The effect on bleeding time was detectable in the majority of animals within 4 hours from conjugated estrogen injection, reached its maximum at 24 hours, and returned to preinjection values within 72 hours from conjugated estrogen injection. Estrogen administration did not influence the generation of vascular PGI2. It is concluded that the model of extensive renal ablation in the rat is a suitable one to study changes in primary hemostasis in chronic renal failure and that the effect of estrogens on primary hemostasis in uremia is not mediated by changes in vascular PGI2.
Zoja
C
C
Mario Negri Institute for Pharmacological Research, Bergamo, Italy.
Viganò
G
G
Bergamelli
A
A
Benigni
A
A
de Gaetano
G
G
Remuzzi
G
G
D000818:Animals; D001760:Bleeding Time; D003404:Creatinine / Q000097:blood; D011464:Epoprostenol / Q000097:blood*; D004966:Estrogens, Conjugated (USP) / Q000494:pharmacology*; D006400:Hematocrit; D006487:Hemostasis / Q000187:drug effects; D007676:Kidney Failure, Chronic / Q000097:blood / Q000503:physiopathology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D004966:Estrogens, Conjugated (USP); D003404:Creatinine; D011464:Epoprostenol