Comparison of cardiorespiratory reflexes in NK 1 receptor knockout, heterozygous and wild-type mice in vivo

Abstract

Neurokinin-1 receptors (NK 1) are present within the nucleus of the solitary tract, a nucleus which plays a vital role in cardiovascular and respiratory homeostasis. We compared the efficacy of the baroreceptor and pulmonary chemoreflexes between NK 1 knockout, heterozygous and wild-type urethane-anaesthetised mice. The magnitude of the baroreceptor reflex mediated bradycardia, induced by a phenylephrine induced pressor response, was significantly greater in NK 1 knockout mice ( P<0.001) compared to heterozygous and wild-type animals. In comparison, administration of an NK 1 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 differences in the magnitude of the reflex evoked falls in heart rate, arterial pressure, or respiratory depression between the three groups of mice when the pulmonary chemoreflex was evoked with right atrial injections of phenylbiguanide. It is concluded that the baroreceptor reflex pathway over-compensates for the lack of NK 1 receptors in knockout mice. Plausible mechanisms accounting for the enhanced baroreceptor reflex responsiveness in NK 1 knockout animals are discussed.