Differential inhibition by aspirin of platelet thromboxane and renal prostaglandins in the rat.
Aspirin (ASA) beside inhibiting platelet thromboxane A2 (TxA2) can suppress the formation of renal prostacyclin (PGI2) and prostaglandin E2 (PGE2) which play a crucial role in the control of renal hemodynamics. Previous studies based on urinary PG measurements have suggested that p.o. ASA can spare renal cyclooxygenase. We wanted to establish by direct measurement whether p.o. ASA has a renal sparing effect and to establish to which extent changes in renal cyclooxygenase activity can be predicted measuring urinary excretion of 6-keto-PGF1 alpha and PGE2. Our results showed that in normal rats 10 mg/kg of ASA given p.o. partially inhibits platelet TxA2 formation (measured as serum TxB2) and does not inhibit glomerular and medullary PGI2 and PGE2 synthesis. Higher doses of ASA (30-200 mg/kg) effectively and completely inhibit platelet TxA2 independently if given p.o. or i.v., and also inhibit glomerular and medullary PG synthesis. The kinetics of the effect of ASA on platelet vs. renal cyclooxygenase is different: the inhibition being irreversible in platelets, but rapidly reversible in glomeruli and medulla. Six hours after the administration of 10 and 30 mg/kg i.v. and 30 mg/kg p.o., kidney cyclooxygenase activity recovers completely. This transient inhibition of renal cyclooxygenase is not reflected by urinary excretion of 6-keto-PGF1 alpha and PGE2 (6- and 24-hr collection periods). In conclusion our present results indicate that doses of ASA enough to inhibit platelet TxA2, transiently inhibit glomerular and medullary PGI2 and PGE2. Although the inhibitory effect on platelets is long lasting, the effect on renal cyclooxygenase is transient and rapidly reversible.(ABSTRACT TRUNCATED AT 250 WORDS)
Livio
M
M
Mario Negri Institute for Pharmacological Research, Bergamo, Italy.
Benigni
A
A
Zoja
C
C
Begnis
R
R
Morelli
C
C
Rossini
M
M
Garattini
S
S
Remuzzi
G
G
D015121:6-Ketoprostaglandin F1 alpha / Q000652:urine*; D000284:Administration, Oral; D000818:Animals; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology*; D001792:Blood Platelets / Q000032:analysis / Q000187:drug effects*; D016861:Cyclooxygenase Inhibitors; D015232:Dinoprostone / Q000652:urine*; D007275:Injections, Intravenous; D007668:Kidney / Q000032:analysis / Q000187:drug effects*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013929:Thromboxane B2 / Q000096:biosynthesis / Q000097:blood*
D016861:Cyclooxygenase Inhibitors; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D015232:Dinoprostone; D001241:Aspirin