Mechanism of action of a new prostaglandin antihypertensive, viprostol [CL 115 347; (dl)-15-deoxy-16-hydroxy-16(alpha/beta)-vinyl-prostaglandin E2 methyl ester]: (I). Vasodilation.
Viprostol [(dl)-15-deoxy-16-hydroxy-16(alpha/beta)-vinyl-prostaglandin E2 methyl ester; CL 115 347], injected directly into coronary, renal, mesenteric, femoral and carotid arteries of the anaesthetized beagle dogs at doses which did not lower the systemic arterial blood pressure, increased blood flow of the vascular beds being studied. Viprostol was as potent as I-prostaglandin E2 (I-PGE2) in the renal bed, but less potent in the other vascular beds. Viprostol was as potent as I-PGE2 in relaxing smooth muscle of the perfused isolated central ear artery of the rabbit. Viprostol maintained its antihypertensive effect in spontaneously hypertensive rats (SHR) pretreated with indomethacin, chlorpheniramine plus cimetidine, atropine or propranolol, suggesting that the vasodilating effects of viprostol were not mediated through the endogenous prostaglandin, histamine, cholinergic nervous system or beta-adrenergic nervous system. The antihypertensive effects of viprostol were not altered in SHR with bilateral nephrectomy or bilaterally ligated ureters, suggesting that the action of viprostol was not dependent on the secretory or excretory functions of the kidneys. In conclusion, viprostol exerts its antihypertensive action mainly by vasodilation in a way similar to the natural PGE2.
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001285:Atropine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002744:Chlorpheniramine / Q000494:pharmacology; D002927:Cimetidine / Q000494:pharmacology; D015232:Dinoprostone / Q000031:analogs & derivatives; D004285:Dogs; D004347:Drug Interactions; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009392:Nephrectomy; D011433:Propranolol / Q000494:pharmacology; D011458:Prostaglandins E / Q000494:pharmacology; D011459:Prostaglandins E, Synthetic / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D011918:Rats, Inbred SHR; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D012039:Regional Blood Flow / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*
D000959:Antihypertensive Agents; D011458:Prostaglandins E; D011459:Prostaglandins E, Synthetic; D011943:Receptors, Adrenergic, beta; D002744:Chlorpheniramine; D001285:Atropine; D002927:Cimetidine; D011433:Propranolol; D015232:Dinoprostone; C034232:viprostol; D007213:Indomethacin