EFFECTS OF CICLETANINE ON PROSTAGLANDIN I-2 AND E-2 LEVELS IN PATIENTS WITH ESSENTIAL-HYPERTENSION

Cicletanine is a new antihypertensive drug that seems to stimulate the synthesis of prostaglandin (PG) I-2. However, there is little evidenc e that cicletanine increases the level of PGI(2) in the systemic blood of human subjects long-term. To investigate the antihypertensive mech anism of cicletanine, we measured serially the systemic blood pressure and the levels of both 6-keto-PGF(1 alpha) (a stable metabolite of PG I(2)) and PGE(2) in plasma and urine after administration of cicletani ne. Nine patients with essential hypertension on a diet with sodium in take 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 liqu id chromatography, and measured by radioimmunoassay. Cicletanine decre ased blood pressure without reflexial tachycardia. The plasma levels o f 6-keto-PGF(1 alpha) were slightly, but significantly, higher at 3 h after the administration of cicletanine on both days 1 and 7 of admini stration (on day 1, 3.88 +/- 1.44 pg/mL and on day 7, 4.07 +/- 0.76, m eans +/- SD, both P < .05 v before administration on day 1) than befor e administration on day 1 (3.21 +/- 1.25 pg/mL). Plasma PGE(2) was hig her 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 excret ion of the two PGs; the increased PG levels partly account for the inc reased natriuresis in the first 3 days. The antihypertensive effects o f cicletanine taken for 1 week were based on natriuresis caused by inc reased systemic synthesis of the vasodilator PGI(2) and partly by the increased renal synthesis of PGI(2) and PGE(2). (C) 1997 American Jour nal of Hypertension, Ltd.