Opiate analogs, substance P, and baroreceptor reflexes in the rabbit

The putative transmitters, enkephalins and substance P, and their binding sites have been identified in the nucleus of the solitary tract. Their role in the modulation of baroreceptor reflex activity is the subject of this study in the rabbit. A stable decarboxy analog of leu-enkephalin, RX 783016, which has mu receptor specificity, was used to attenuate the baroreflex sensitivity to intravenous phenylephrine. RX 783016, 50 micrograms/kg intracisternally, did not alter resting heart rate of blood pressure. Intravenous administration of the opiate receptor antagonist, naloxone, prevented the effects of RX 783016. Naloxone given alone significantly increased reflex sensitivity. Substance P given intracisternally in low doses (1 to 10 ng/kg) caused a dose-dependent pressor response, which was reduced by pretreatment with morphine and enhanced by naloxone. Bilateral sinoaortic denervation also enhanced the pressor response to substance P, but after deafferentation, naloxone had no further effect. It is proposed that enkephalin-containing neurons, acting through mu receptors, and substance P neurons influence baroreceptor reflex activity by modulating respectively the primary and second order neurons of the baroreceptor reflex.