The effect of a leukotriene receptor antagonist, FPL 55712, on estrogen-induced uterine hyperemia in the nonpregnant rabbit.
Estrogen results in delayed uterine hyperemia. We postulate that the leukotrienes may be the mediators of the uterine vascular responses to estrogen. To test this hypothesis, we gave FPL 55712, a selective leukotriene antagonist, to estrogen-primed, nonpregnant rabbits and measured regional blood flows by the radioactive microsphere technique. In 10 chronically catheterized animals, blood flows were measured in the control condition (C), and again 2 hours after systemic administration of estradiol (EST). Thirty minutes before administration of estradiol, five animals received systemic FPL 55712, whereas five animals received vehicle only. The vehicle group showed the expected increase in uterine blood flow from 0.62 +/- 0.1 to 2.72 +/- 0.4 ml X min-1 X gm-1, and decrease in uterine resistance from 144 +/- 31 to 34 +/- 8 peripheral resistance units (PRU) X gm, with a resistance ratio (estradiol/C) of 0.23 +/- 0.01. Unexpectedly, the FPL 55712 group showed a further increase in uterine blood flow from 0.66 +/- 0.1 to 4.60 +/- 0.3 ml X min-1 X gm-1, and a decrease in resistance from 133 +/- 25 to 17 +/- 1 PRU X gm, with a resistance ratio of 0.13 +/- 0.02. The leukotriene antagonist FPL 55712 potentiates estrogen-induced uterine hyperemia by 77% (P less than 0.001). These data suggest that leukotrienes do not mediate, but rather inhibit, the uterine vascular responses to estrogen.
D000818:Animals; D002867:Chromones / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology / Q000502:physiology*; D005260:Female; D006940:Hyperemia / Q000503:physiopathology*; D011817:Rabbits; D012039:Regional Blood Flow / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects; D013189:SRS-A / Q000037:antagonists & inhibitors* / Q000502:physiology; D014599:Uterus / Q000098:blood supply*; D014655:Vascular Resistance / Q000187:drug effects
D002867:Chromones; D004967:Estrogens; D013189:SRS-A; C006312:FPL 55712