COMPARISON OF CARDIORESPIRATORY REFLEXES IN NK1 RECEPTOR KNOCKOUT, HETEROZYGOUS AND WILD-TYPE MICE IN-VIVO

Neurokinin-1 receptors (NK1) are present within the nucleus of the sol itary tract, a nucleus which plays a vital role in cardiovascular and respiratory homeostasis. We compared the efficacy of the baroreceptor and pulmonary chemoreflexes between NK1 knockout, heterozygous and wil d-type urethane-anaesthetised mice.The magnitude of the baroreceptor r eflex mediated bradycardia, induced by a phenylephrine induced presser response, was significantly greater in NK1 knockout mice (P < 0.001) compared to heterozygous and wild-type animals. In comparison, adminis tration of an NK1 antagonist, CP-99,994 (1.5 mg/kg i.v.) to wild-type animals, had no significant effect on baroreceptor reflex performance. In contrast to the baroreceptor reflex, there were no significant dif ferences in the magnitude of the reflex evoked falls in heart rate, ar terial pressure, or respiratory depression between the three groups of mice when the pulmonary chemoreflex was evoked with right atrial inje ctions of phenylbiguanide. It is concluded that the baroreceptor refle x pathway over-compensates for the lack of NK1 receptors in knockout m ice. Plausible mechanisms accounting for the enhanced baroreceptor ref lex responsiveness in NK1 knockout animals are discussed. (C) 1998 Els evier Science B.V. All rights reserved.