The diuretic effects of CL 115,129 (d,1-15-deoxy-16-hydroxy-16(alpha/beta)-vinyl-prostaglandin E2) and l-prostaglandin E2 in dogs.
CL 115,129, the corresponding carboxylic acid and major metabolite of CL 115,347 (d,1-15-deoxy-16-hydroxy-16(alpha/beta)-vinyl-prostaglandin E2 methyl ester), a potent orally and transdermally long acting antihypertensive agent, infused at 0.1 microgram/kg/min into the left renal artery of sodium pentobarbital anesthetized beagle dogs increased urinary volume, sodium (Na+), potassium (K+) and chloride (Cl-) excretion of the left kidney 289, 201, 101 and 229%, respectively, over the 30 min vehicle-treated control periods. At 0.3 microgram/kg/min CL 115,129 caused a 475 and 336% increase in urinary volume and Na+, respectively. l-Prostaglandin E2 (l-PGE2) infused at 0.1 microgram/kg/min into the left renal artery increased urinary volume, Na+, K+ and Cl- excretion of the left kidney of anesthetized beagle dogs 416, 234, 112 and 255%, respectively, over the control. Both CL 115,129 and l-PGE2 did not affect the systemic arterial blood pressure or the electrolyte excretion of the contralateral kidney. It is concluded that in contrast to other conventional vasodilators, which may cause severe water and electrolyte retention, CL 115,347, via its metabolite CL 115,129, may cause diuresis and natriuresis in many clinical settings when used as an antihypertensive.
D000818:Animals; D015232:Dinoprostone / Q000031:analogs & derivatives; D004231:Diuresis / Q000187:drug effects*; D004285:Dogs; D005260:Female; D007668:Kidney / Q000187:drug effects; D008297:Male; D011458:Prostaglandins E / Q000494:pharmacology*; D011459:Prostaglandins E, Synthetic / Q000494:pharmacology*
D011458:Prostaglandins E; D011459:Prostaglandins E, Synthetic; C034231:15-deoxy-16-hydroxy-16-vinylprostaglandin E2; D015232:Dinoprostone