Abstract

CL 115,347 [dl-15-deoxy-16-hydroxy-16(alpha/beta)-vinyl prostaglandin E2 methyl ester] has a broad spectrum of antihypertensive activity in many animal hypertension models in every species tested. In conscious spontaneously hypertensive rats, CL 115,347 at 0.25 to 10 mg/kg orally produced 31 to 53 mm Hg lowering of the mean arterial blood pressure (MABP) with a duration of action of 1 to greater than 8 hr. When applied transdermally, CL 115,347 was more potent and longer acting than by the oral route. At 0.03 to 1 mg/kg, topically applied CL 115,347 lowered MABP of spontaneously hypertensive rats 27 to 46 mm Hg. Duration of action was greater than 6 to greater than 24 hr. CL 115,347 was also active in conscious normotensive rats (-27 mm Hg), deoxycorticosterone-salt-induced hypertensive rats (-51 mm Hg) and aorta-coarcted hypertensive rats (-52 mm Hg) when tested at 1 mg/kg orally. At 3 mg/kg orally, CL 115,347 lowered MABP of Dahl "S" salt-sensitive rats 55 mm Hg. CL 115,347 orally and s.c. lowered MABP in two-kidney, one-clip Goldblatt renal hypertensive dogs and was accompanied by tachycardia. CL 115,347, at 0.1 and 0.2 mg/kg orally, maximally lowered the systolic blood pressure of conscious rhesus monkeys 33 to 63 mm Hg with only a slight increase in heart rate. Therefore, CL 115,347 was antihypertensive in animals with low, normal and high plasma renin activity. The present findings suggest that CL 115,347 may be useful for the treatment of human hypertension.