Cyclic phosphatidic acid stimulates respiration without producing vasopressor or tachycardiac effects in rats

The effects of a novel lipid mediator, cyclic phosphatidic acid (cPA), on respiratory and cardiovascular functions were examined in anesthetized rats. Intravenous (i.v.) administration of 3-O-carba-oleoyl-cPA at doses of 130 and 390 microg/kg produced dose-dependent increases in tidal volume and respiratory frequency, resulting in an increase in total ventilation. Heart rate was slightly decreased at a dose of 390 microg/kg, while systemic arterial pressure was not affected. Bilateral section of vagi and carotid sinus nerves designed to eliminate major regulatory inputs from the peripheral afferents to the respiratory center reduced these responses, but did not abolish them. These results indicate that cPA stimulates respiration, via central and peripheral mechanisms acting on the central respiratory rhythm generator in the brain stem. Administration of cPA may be of therapeutic value as a respiratory stimulant without producing vasopressor or tachycardiac effects, for treatment of respiratory disorders.