SHORT-TERM INCREASE IN PROSTAGLANDIN I-2 SYNTHESIS CAUSED BY CICLETANINE IN PATIENTS WITH ESSENTIAL-HYPERTENSION

Cicletanine is a new antihypertensive drug that stimulates renal and v ascular synthesis of prostaglandin (PG) I-2 in experimental animals. H owever, there is little evidence that cicletanine increases the level of PGI(2) in systemic blood of human subjects. To investigate the shor t-term antihypertensive mechanism of cicletanine, we measured serially the systemic blood pressure, the levels of 6-keto-PGF(1 alpha) (a sta ble metabolite of PGI(2)) and PGE(2), and renin activity in plasma aft er administration of the drug. Nine patients with essential hypertensi on on a diet without severe sodium restriction took 100 mg of the drug by mouth. Systemic blood pressure was measured hourly for 24 h before and after cicletanine administration. The two PGs of interest were ex tracted, purified by high pressure liquid chromatography, and measured by radioimmunoassay. Cicletanine decreased blood pressure 3 and 6 h a fter administration and increased the plasma level of 6-keto-PGF(1 alp ha). The increase in 6-keto-PGF(1 alpha) was small but significant (me an +/- SD, from 3.21 +/- 1.26 to 3.88 +/- 1.44 and later 4.15 +/- 1.08 pg/mL by 3 and 6 h after administration; P < .05 and .01, respectivel y). The level of PGE, had increased at 3 h after administration but re turned to baseline by 6 h. Plasma renin activity was increased only at 24 h after administration. Cicletanine increased systemic PGI(2) leve ls short-term, producing an antihypertensive effect in patients with e ssential hypertension.