Cocaine- and amphetamine-regulated transcript peptide attenuates baroreflex in the rat

Cocaine- and amphetamine-regulated transcript (CART) was first identified in the rat striatum where the levels were up regulated following cocaine and amphetamine administration. In situ and immunohistochemical studies have since revealed an extensive distribution of CART peptide (CARTp) in the rat brain, spinal cord and peripheral tissues. In particular, a dense plexus of CART-immunoreactive fibers is noted in the nucleus of the solitary tract (NTS). As CARTimmunoreactivity is detectable in a large population of primary afferent neurons in the nodose ganglia, the latter may give rise to the dense networks of CART-fibers in the NTS. The present study was undertaken to evaluate the hypothesis that CARTp may alter baroreceptor function in rats. Male Sprague-Dawley rats, weighing 350–375 g, were anesthetized with urethane (1.2 g/kg, IP). The femoral artery and vein were cannulated for blood pressure measurement and for intravenous administration of phenylephrine (7–10μg/kg). The latter was injected every 10 min to elicit a baroreflex. CARTp (55–102) at the doses of 0.1, 0.3, 1, and 3 nmol by intracisternal or bilateral intra-NTS injection consistently attenuated the bradycardia in response to baroreflex induced by IV phenylephrine. In contrast, CART antibody (1:500) potentiated the bradycardia in response to phenylephrine-induced baroreflex. Microinjection of saline, normal rabbit serum, or concomitant injection of CARTp and CART antibody into the NTS caused no significant change of phenylephrine-induced baroreflex. The results together with the presence of dense networks of CART-fibers in the NTS raise the possibility that the peptide may modulate baroreflex.