Low-dose aspirin. I. Effect on angiotensin II pressor responses and blood prostaglandin concentrations in pregnant women sensitive to angiotensin II.
Decreased incidence of proteinuric hypertension after low-dose aspirin therapy is hypothesized to be a consequence of selective thromboxane A2 inhibition and sparing of prostacyclin. This study was designed to ascertain if low-dose aspirin therapy (81 mg/day for 1 week) alters vascular refractoriness to angiotensin II and the prostacyclin/thromboxane A2 ratio in pregnant women sensitive to angiotensin II (n = 17). Low-dose aspirin increased the effective pressor dose of angiotensin II from 5.9 +/- 2.4 to 10.2 +/- 5.5 ng/kg/min (p less than 0.01, mean +/- SD). Platelet-derived serum thromboxane B2 (a metabolite of thromboxane A2), a measure of therapy compliance, decreased from 1804 +/- 1771 to 132 +/- 206 pg/ml (p less than 0.01). Plasma thromboxane B2 decreased from 130 +/- 107 to 19 +/- 12 pg/ml (p less than 0.01). Inhibition was not selective because 6-keto-prostaglandin F1 alpha (a metabolite of prostacyclin) also decreased from 243 +/- 90 to 163 +/- 90 pg/ml (p = 0.039) and prostaglandin E2 was reduced from 155 +/- 67 to 95 +/- 40 pg/ml (p = 0.014). Decreases in thromboxane B2, however, were significantly greater (75% +/- 19%) than decreases in 6-keto-prostaglandin F1 alpha (21% +/- 33%) or prostaglandin E2 (29% +/- 36%); thus the 6-keto-prostaglandin F1 alpha/thromboxane B2 ratio increased from 3.1 +/- 2.0 to 12.4 +/- 9.9 (p less than 0.01). Although low-dose aspirin increases the effective pressor dose of angiotensin II, it does not return to normal pregnancy values. This observation is consistent with the hypothesis that this represents only a partial selective prostaglandin inhibition.
Spitz
B
B
Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas 75235.
Magness
R R
RR
Cox
S M
SM
Brown
C E
CE
Rosenfeld
C R
CR
Gant
N F
NF
D000804:Angiotensin II / Q000627:therapeutic use*; D001241:Aspirin / Q000008:administration & dosage* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects*; D004334:Drug Administration Schedule; D004351:Drug Resistance; D005260:Female; D006801:Humans; D006973:Hypertension / Q000517:prevention & control; D009994:Osmolar Concentration; D010298:Parity; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000517:prevention & control; D011453:Prostaglandins / Q000097:blood*; D013929:Thromboxane B2 / Q000097:blood
D011453:Prostaglandins; D000804:Angiotensin II; D013929:Thromboxane B2; D001241:Aspirin