A new class of antihypertensive neutral lipid: 1-alkyl-2-acetyl-sn-glycerols, a precursor of platelet activating factor.
A new type of neutral lipid is described that possesses hypotensive activity in genetic hypertensive (SHR) and normotensive (WKY) rats. 1-Alkyl-2-acetyl-sn-glycerols and 1-alkyl-2-propionyl-sn-glycerols are both equally effective in eliciting the hypotensive response. Requirement for the 1-alkyl and 2-acetyl or 2-propionyl structure of the active isomer was documented by the negative responses obtained with closely related neutral lipid analogs (1-alkyl-2-acyl-, 1-alkyl-3-acetyl-, 1-acyl-2-acetyl-, 1-alkyl-2,3-diacetyl-, and 1-alkyl-glycerols). Although less potent than PAF (1-alkyl-2-acetyl-sn-glycero-3-phosphocholine), the 1-alkyl-2-acetyl-sn-glycerols produce a response of significantly longer duration and may have fewer immediate side effects than PAF. The mechanism for the biological activity is unknown; however, we have demonstrated previously that the enzymatic synthesis of 1-alkyl-2-acetyl-sn-glycerols to PAF occurs via a specific cholinephosphotransferase and therefore the observed blood pressure response might be due to the conversion of the neutral lipid precursor to PAF in vivo.
D000818:Animals; D000959:Antihypertensive Agents / Q000138:chemical synthesis*; D001681:Biological Assay; D001794:Blood Pressure / Q000187:drug effects; D006973:Hypertension / Q000503:physiopathology; D010972:Platelet Activating Factor / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology; D051381:Rats; D011922:Rats, Mutant Strains; D013329:Structure-Activity Relationship
D000959:Antihypertensive Agents; D010972:Platelet Activating Factor