Effect of ZK 36 374 on blood pressure, diuresis, plasma renin activity and urinary excretion of prostaglandin E2 and sodium.

ZK 36 374 is a chemically stable prostacyclin analogue which has been demonstrated to be a potent vasodilator. The effects of the drug on blood pressure, plasma renin activity, diuresis and urinary excretion of prostaglandin E2 and sodium, were studied on the 1st and 7th days of treatment and a week after the end of the administration to rats submitted to the following experimental situations: Goldblatt 2k-1c, Goldblatt 2k-1c + 5% NaCl loading, 5% NaCl loading, and controls. ZK 36 374 was continuously administered during one week by an osmotic pump subcutaneously implanted and connected to the right jugular vein. Twenty four hours after the pump implantation, blood pressure decreased in the three experimental groups. At the 7th day, pressure remained at similar levels except in NaCl loaded rats where an increase was observed. At the 15th day pressure levels returned to pretreatment values. On the 7th day of treatment urinary PGE2 showed higher values than pretreatment ones, to return to pretreatment at the 15 day. Sodium excretion showed an increase on the 7th day and was even higher on the 15th day. Plasma renin activity levels remained unchanged during the treatment except in the Goldblatt 2k-1c group which showed a significant fall at the 7th day. All the changes described on the 1st day of treatment might be related to counteraction of the blood pressure decrease on the same day.