Effects of lysophosphatidic acids and their structural analogs on arterial blood pressure of cats.

On intravenous injection into cats, lysophosphatidic acid elicited a biphasic change in arterial blood pressure: sharp hypotension followed immediately by hypertension. Respiration was greatly disturbed immediately after injection of lysophosphatidic acid, and remained stimulated for a long period, and the heart rate increased during the period of hypertension. Unsaturated lysophosphatidic acids were more potent in evoking hypertension than saturated ones. The hypotensive activity of 1-palmitoyl-2-0-acetyl-sn-glycero-3-phosphate was about half that of 1-palmitoyl-2-lyso-sn-glycero-3-phosphate (lysophosphatidic acid). Elongation of the acyl chain at the sn-2-position of the glycerol moiety resulted in progressive reduction in the hypotensive activity. Chemically modified analogs with a head group, such as phosphoryl-methanol, ethanol, propanol and choline, had little or no activity. However, sn-2-acetyl-analogs of lyso-phosphatidyl cholines had hypotensive activity. 1-0-Hexadecyl-2-lyso-sn-glycero-3-phosphate, an alkyl-lyso-phosphatidic acid, had much stronger hypotensive activity than the corresponding acyl-lysophosphatidic acid, like its sn-2-0-acetyl analog. These structure-activity relationships of lysophosphatidic acids indicate the existence of their specific binding sites on cardiovascular cells.