Effects of low-dose aspirin on responses to furosemide.
We assessed the effects of low-dose aspirin (0.5 and 15 mg/kg/d) on renal prostaglandin synthesis and action in healthy volunteers using intravenous furosemide as a stimulus. Inhibition of platelet cyclo-oxygenase was assessed by changes in serum thromboxane B2 (TXB2) level. After one week of treatment, ten healthy subjects did not show any change in weight, blood pressure, or diuretic and natriuretic responses to furosemide with either dose of aspirin. Serum TXB2 level was reduced to 3% of control by aspirin 0.5 mg/kg/d and to 0.1% by the higher dose. In contrast, urine excretion of TXB2 was only reduced to 68% and 51% of the placebo value, whereas 6-keto-prostaglandin F1 alpha (6kPGF1 alpha) excretion was not decreased by either dose. Furosemide produced a transient increase in excretion rates of TXB2 and 6kPGF1 alpha that was of lesser duration than the diuretic response. These transient increases were slightly reduced by aspirin. Baseline plasma renin activity was not affected by either dose of aspirin. The brisk increment in plasma renin activity seen ten minutes after furosemide, as well as later values (30 and 240 min) were not changed by aspirin. We conclude that chronic low-dose aspirin can profoundly affect platelet PG production without affecting stimulated renal PGI2 production or plasma renin activity. There is a modest reduction in urine TXB2 excretion that is consistent with a primarily renal source of this metabolite.
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000328:Adult; D001241:Aspirin / Q000008:administration & dosage*; D001792:Blood Platelets / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D004537:Eicosanoic Acids / Q000652:urine; D004573:Electrolytes / Q000378:metabolism; D005260:Female; D005665:Furosemide / Q000494:pharmacology*; D006801:Humans; D008297:Male; D011863:Radioimmunoassay; D012083:Renin / Q000097:blood; D013928:Thromboxane A2 / Q000097:blood; D013997:Time Factors
D004537:Eicosanoic Acids; D004573:Electrolytes; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; D005665:Furosemide; D012083:Renin; D001241:Aspirin