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  • Title: Effects of cicletanine on prostaglandin I2 and E2 levels in patients with essential hypertension.
    Author: Yasu T, Imanishi M.
    Journal: Am J Hypertens; 1997 Jul; 10(7 Pt 1):750-5. PubMed ID: 9234829.
    Abstract:
    Cicletanine is a new antihypertensive drug that seems to stimulate the synthesis of prostaglandin (PG) I2. However, there is little evidence that cicletanine increases the level of PGI2 in the systemic blood of human subjects long-term. To investigate the antihypertensive mechanism of cicletanine, we measured serially the systemic blood pressure and the levels of both 6-keto-PGF1alpha (a stable metabolite of PGI2) and PGE2 in plasma and urine after administration of cicletanine. Nine patients with essential hypertension on a diet with sodium intake of 120 mEq/day took 100 mg of the drug orally daily every day for 1 week. Systemic blood pressure was measured hourly for 24 h on day 7 of the control period and on days 1 and 7 of the cicletanine period. The two PGs of interest were extracted, purified by high pressure liquid chromatography, and measured by radioimmunoassay. Cicletanine decreased blood pressure without reflexial tachycardia. The plasma levels of 6-keto-PGF1alpha were slightly, but significantly, higher at 3 h after the administration of cicletanine on both days 1 and 7 of administration (on day 1, 3.88 +/- 1.44 pg/mL and on day 7, 4.07 +/- 0.76, means +/- SD, both P < .05 v before administration on day 1) than before administration on day 1 (3.21 +/- 1.25 pg/mL). Plasma PGE2 was higher before and at 3 h after administration on day 7 than at 12 noon on day 7 of the control period. Cicletanine increased the urinary excretion of the two PGs; the increased PG levels partly account for the increased natriuresis in the first 3 days. The antihypertensive effects of cicletanine taken for 1 week were based on natriuresis caused by increased systemic synthesis of the vasodilator PGI2 and partly by the increased renal synthesis of PGI2 and PGE2.
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